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  • 1. Andersson, M.
    et al.
    Johansson, Lennart
    Umeå University, Faculty of Medicine, Department of Radiation Sciences, Radiation Physics.
    Minarik, D.
    Mattsson, S.
    Leide-Svegborn, S.
    Absorbed dose to the urinary bladder wall for different radiopharmaceuticals using dynamic S-values2013In: European Journal of Nuclear Medicine and Molecular Imaging, ISSN 1619-7070, E-ISSN 1619-7089, Vol. 40, no Supplement 2, p. S161-S161Article in journal (Other academic)
  • 2. Andersson, M.
    et al.
    Johansson, Lennart
    Umeå University, Faculty of Medicine, Department of Radiation Sciences, Radiation Physics.
    Minarik, D.
    Mattsson, S.
    Leide-Svegborn, S.
    An internal radiation dosimetry computer program, IDAC 2.0, for estimation of patient doses from radiopharmaceuticals2014In: Radiation Protection Dosimetry, ISSN 0144-8420, E-ISSN 1742-3406, Vol. 162, no 3, p. 299-305Article in journal (Refereed)
    Abstract [en]

    The internal dosimetry computer program internal dose assessment by computer (IDAC) for calculations of absorbed doses to organs and tissues as well as effective doses to patients from examinations with radiopharmaceuticals has been developed. The new version, IDAC2.0, incorporates the International Commission on Radiation Protection (ICRP)/ICRU computational adult male and female voxel phantoms and decay data from the ICRP publication 107. Instead of only 25 source and target regions, calculation can now be made with 63 source regions to 73 target regions. The major advantage of having the new phantom is that the calculations of the effective doses can be made with the latest tissue weighting factors of ICRP publication 103. IDAC2.0 uses the ICRP human alimentary tract (HAT) model for orally administrated activity and for excretion through the gastrointestinal tract and effective doses have been recalculated for radiopharmaceuticals that are orally administered. The results of the program are consistent with published data using the same specific absorption fractions and also compared with published data from the same computational phantoms but with segmentation of organs leading to another set of specific absorption fractions. The effective dose is recalculated for all the 34 radiopharmaceuticals that are administered orally and has been published by the ICRP. Using the new HAT model, new tissue weighting factors and the new adult computational voxel phantoms lead to an average effective dose of half of its earlier estimated value. The reduction mainly depends on electron transport simulations to walled organs and the transition from the stylised phantom with unrealistic interorgan distances to more realistic voxel phantoms.

  • 3. Andersson, M.
    et al.
    Johansson, Lennart
    Umeå University, Faculty of Medicine, Department of Radiation Sciences, Radiation Physics.
    Minarik, D.
    Mattsson, S.
    Leide-Svegborn, S.
    IDAC2.0 a new generation of internal dosimetric calculations for diagnostic examinations in nuclear medicine using the adult ICRP/ICRU reference computational voxel phantoms2013In: European Journal of Nuclear Medicine and Molecular Imaging, ISSN 1619-7070, E-ISSN 1619-7089, Vol. 40, no Supplement 2, p. S175-S176Article in journal (Other academic)
  • 4. Andersson, M.
    et al.
    Minarik, D.
    Johansson, Lennart
    Umeå University, Faculty of Medicine, Department of Radiation Sciences.
    Mattsson, S.
    Leide-Svegborn, S.
    A new method to generate dose coefficients for the source region "other organs and tissues"2014In: European Journal of Nuclear Medicine and Molecular Imaging, ISSN 1619-7070, E-ISSN 1619-7089, Vol. 41 2, p. S237-S237Article in journal (Other academic)
  • 5. Andersson, Martin
    et al.
    Johansson, Lennart
    Umeå University, Faculty of Medicine, Department of Radiation Sciences, Radiation Physics.
    Eckerman, Keith
    Mattsson, Sören
    IDAC-Dose 2.1, an internal dosimetry program for diagnostic nuclear medicine based on the ICRP adult reference voxel phantoms2017In: EJNMMI Research, ISSN 2191-219X, E-ISSN 2191-219X, Vol. 7, article id 88Article in journal (Refereed)
    Abstract [en]

    Background: To date, the estimated radiation-absorbed dose to organs and tissues in patients undergoing diagnostic examinations in nuclear medicine is derived via calculations based on models of the human body and the biokinetic behaviour of the radiopharmaceutical. An internal dosimetry computer program, IDAC-Dose2.1, was developed based on the International Commission on Radiological Protection (ICRP)-specific absorbed fractions and computational framework of internal dose assessment given for reference adults in ICRP Publication 133. The program uses the radionuclide decay database of ICRP Publication 107 and considers 83 different source regions irradiating 47 target tissues, defining the effective dose as presented in ICRP Publications 60 and 103. The computer program was validated against another ICRP dosimetry program, Dose and Risk Calculation (DCAL), that employs the same computational framework in evaluation of occupational and environmental intakes of radionuclides. IDAC-Dose2.1 has a sub-module for absorbed dose calculations in spherical structures of different volumes and composition; this sub-module is intended for absorbed dose estimates in radiopharmaceutical therapy. For nine specific alpha emitters, the absorbed dose contribution from their decay products is also included in the committed absorbed dose calculations. Results: The absorbed doses and effective dose of I-131-iodide determined by IDAC-Dose2.1 were validated against the dosimetry program DCAL, showing identical results. IDAC-Dose2.1 was used to calculate absorbed doses for intravenously administered F-18-FDG and orally administered Tc-99m-pertechnetate and I-131-iodide, three frequently used radiopharmaceuticals. Using the tissue weighting factors from ICRP Publication 103, the effective dose per administered activity was estimated to be 0.016 mSv/MBq for F-18-FDG, 0.014 mSv/MBq for Tc-99m-pertechnetate, and 16 mSv/MBq for I-131-iodide. Conclusions: The internal dosimetry program IDAC-Dose2.1 was developed and applied to three radiopharmaceuticals for validation against DCAL and to generate improved absorbed dose estimations for diagnostic nuclear medicine using specific absorbed fraction values of the ICRP computational voxel phantoms. The sub-module for absorbed dose calculations in spherical structures 1 mm to 9 cm in diameter and different tissue composition was included to broaden the clinical usefulness of the program. The IDAC-Dose2.1 program is free software for research and available for download at http://www.idac-dose.org.

  • 6. Andersson, Martin
    et al.
    Johansson, Lennart
    Umeå University, Faculty of Medicine, Department of Radiation Sciences, Radiation Physics.
    Mattsson, Sören
    Minarik, David
    Leide-Svegborn, Sigrid
    Organ doses and effective dose for five pet radiopharmaceuticals2016In: Radiation Protection Dosimetry, ISSN 0144-8420, E-ISSN 1742-3406, Vol. 169, no 1-4, p. 253-258Article in journal (Refereed)
    Abstract [en]

    Diagnostic investigations with positron-emitting radiopharmaceuticals are dominated by 18F-fluorodeoxyglucose (18F-FDG), but other radiopharmaceuticals are also commercially available or under development. Five of them, which are all clinically important, are 18F-fluoride, 18F-fluoroethyltyrosine (18F-FET), 18F-deoxyfluorothymidine (18F-FLT), 18F-fluorocholine (18F-choline) and 11C-raclopride. To estimate the potential risk of stochastic effects (mainly lethal cancer) to a population, organ doses and effective dose values were updated for all five radiopharmaceuticals. Dose calculations were performed using the computer program IDAC2.0, which bases its calculations on the ICRP/ICRU adult reference voxel phantoms and the tissue weighting factors from ICRP publication 103. The biokinetic models were taken from ICRP publication 128. For organ doses, there are substantial changes. The only significant change in effective dose compared with previous estimations was a 46 % reduction for 18F-fluoride. The estimated effective dose in mSv MBq−1 was 1.5E−02 for 18F-FET, 1.5E−02 for 18F-FLT, 2.0E−02 for 18F-choline, 9.0E−03 for 18F-fluoride and 4.4E−03 for 11C-raclopride.

  • 7. Andersson, Martin
    et al.
    Mattsson, Soren
    Johansson, Lennart
    Umeå University, Faculty of Medicine, Department of Radiation Sciences, Radiation Physics.
    Leide-Svegborn, Sigrid
    A biokinetic and dosimetric model for ionic indium in humans2017In: Physics in Medicine and Biology, ISSN 0031-9155, E-ISSN 1361-6560, Vol. 62, no 16, p. 6397-6407Article in journal (Refereed)
    Abstract [en]

    This paper reviews biokinetic data for ionic indium, and proposes a biokinetic model for systemic indium in adult humans. The development of parameter values focuses on human data and indium in the form of ionic indium(III), as indium chloride and indium arsenide. The model presented for systemic indium is defined by five different pools: plasma, bone marrow, liver, kidneys and other soft tissues. The model is based on two subsystems: one corresponding to indium bound to transferrin and one where indium is transported back to the plasma, binds to red blood cell transferrin and is then excreted through the kidneys to the urinary bladder. Absorbed doses to several organs and the effective dose are calculated for In-111- and In-113m-ions. The proposed biokinetic model is compared with previously published biokinetic indium models published by the ICRP. The absorbed doses are calculated using the ICRP/ICRU adult reference phantoms and the effective dose is estimated according to ICRP Publication 103. The effective doses for In-111 and In-113m are 0.25 mSv MBq(-1) and 0.013 mSv MBq(-1) respectively. The updated biokinetic and dosimetric models presented in this paper take into account human data and new animal data, which represent more detailed and presumably more accurate dosimetric data than that underlying previous models for indium.

  • 8.
    Andersson, Martin
    et al.
    Medical Radiation Physics, Department of Clinical Sciences Malmö, Lund University, Skåne University Hospital, Malmö, Sweden .
    Minarik, David
    Medical Radiation Physics, Department of Clinical Sciences Malmö, Lund University, Skåne University Hospital, Malmö, Sweden .
    Johansson, Lennart
    Umeå University, Faculty of Medicine, Department of Radiation Sciences, Radiation Physics.
    Mattsson, Soren
    Medical Radiation Physics, Department of Clinical Sciences Malmö, Lund University, Skåne University Hospital, Malmö, Sweden .
    Leide-Svegborn, Sigrid
    Medical Radiation Physics, Department of Clinical Sciences Malmö, Lund University, Skåne University Hospital, Malmö, Sweden .
    Improved estimates of the radiation absorbed dose to the urinary bladder wall2014In: Physics in Medicine and Biology, ISSN 0031-9155, E-ISSN 1361-6560, Vol. 59, no 9, p. 2173-2182Article in journal (Refereed)
    Abstract [en]

    Specific absorbed fractions (SAFs) have been calculated as a function of the content in the urinary bladder in order to allow more realistic calculations of the absorbed dose to the bladder wall. The SAFs were calculated using the urinary bladder anatomy from the ICRP male and female adult reference computational phantoms. The urinary bladder and its content were approximated by a sphere with a wall of constant mass, where the thickness of the wall depended on the amount of urine in the bladder. SAFs were calculated for males and females with 17 different urinary bladder volumes from 10 to 800 mL, using the Monte Carlo computer program MCNP5, at 25 energies of mono-energetic photons and electrons ranging from 10 KeV to 10 MeV. The decay was assumed to be homogeneously distributed in the urinary bladder content and the urinary bladder wall, and the mean absorbed dose to the urinary bladder wall was calculated. The Monte Carlo simulations were validated against measurements made with thermoluminescent dosimeters. The SAFs obtained for a urine volume of 200 mL were compared to the values calculated for the urinary bladder wall using the adult reference computational phantoms. The mean absorbed dose to the urinary wall from F-18-FDG was found to be 77 mu Gy/MBq formales and 86 mu Gy/MBq for females, while for (99)mTc-DTPA the mean absorbed doses were 80 mu Gy/MBq for males and 86 mu Gy/MBq for females. Compared to calculations using a constant value of the SAF from the adult reference computational phantoms, the mean absorbed doses to the bladder wall were 60% higher for F-18-FDG and 30% higher for (99)mTc-DTPA using the new SAFs.

  • 9.
    Boson, Jonas
    et al.
    Umeå University, Faculty of Medicine, Department of Radiation Sciences, Radiation Physics.
    Johansson, Lennart
    Umeå University, Faculty of Medicine, Department of Radiation Sciences, Radiation Physics.
    Ramebäck, Henrik
    Swedish Defence Research Agency, FOI CBRN Defence and Security, SE-901 82 Umeå, Sweden.
    Ågren, Göran
    Swedish Defence Research Agency, FOI CBRN Defence and Security, SE-901 82 Umeå, Sweden.
    Uncertainty in HPGe detector calibrations for in situ gamma-ray spectrometry2009In: Radiation Protection Dosimetry, ISSN 0144-8420, E-ISSN 1742-3406, Vol. 134, no 2, p. 122-129Article in journal (Refereed)
    Abstract [en]

    Semi-empirical methods are often used for efficiency calibrations of in situ gamma-ray spectrometry measurements with high-purity germanium detectors. The intrinsic detector efficiency is experimentally determined for different photon energies and angles of incidence, and a suitable expression for the efficiency is fitted to empirical data. In this work, the combined standard uncertainty of such an efficiency function for two detectors was assessed. The uncertainties in individual efficiency measurements were found to be about 1.9 and 3.1% (with a coverage factor k = 1, i.e. with a confidence interval of about 68%) for the two detectors. The main contributions to these uncertainties were found to originate from uncertainties in source-to-detector distance, source activity and full-energy peak count rate. The standard uncertainties of the fitted functions were found to be somewhat higher than the uncertainty of individual data points, i.e. 5.2 and 8.1% (k = 1). With the introduction of a new expression for the detector efficiency, these uncertainties were reduced to 3.7 and 4.2%, i.e. with up to a factor of two. Note that this work only addresses the uncertainty in the determination of intrinsic detector efficiency.

  • 10.
    Boson, Jonas
    et al.
    Umeå University, Faculty of Medicine, Department of Radiation Sciences, Radiation Physics.
    Plamboeck, Agneta H
    Swedish Defence Research Agency, FOI CBRN Defence and Security, SE-901 82 Umeå, Sweden.
    Ramebäck, Henrik
    Swedish Defence Research Agency, FOI CBRN Defence and Security, SE-901 82 Umeå, Sweden.
    Ågren, Göran
    Swedish Defence Research Agency, FOI CBRN Defence and Security, SE-901 82 Umeå, Sweden.
    Johansson, Lennart
    Umeå University, Faculty of Medicine, Department of Radiation Sciences, Radiation Physics.
    Evaluation of Monte Carlo-based calibrations of HPGe detectors for in situ gamma-ray spectrometry2009In: Journal of Environmental Radioactivity, ISSN 0265-931X, E-ISSN 1879-1700, Vol. 100, no 11, p. 935-940Article in journal (Refereed)
    Abstract [en]

    The aim of this work was to evaluate the use of Monte Carlo-based calibrations for in situ gamma-ray spectrometry. We have performed in situ measurements at five different sites in Sweden using HPGe detectors to determine ground deposition activity levels of (137)Cs from the 1986 Chernobyl accident. Monte Carlo-calculated efficiency calibration factors were compared with corresponding values calculated using a more traditional semi-empirical method. In addition, results for the activity ground deposition were also compared with activity densities found in soil samples. In order to facilitate meaningful comparisons between the different types of results, the combined standard uncertainty of in situ measurements was assessed for both calibration methods. Good agreement, both between the two calibration methods, and between in situ measurements and soil samples, was found at all five sites. Uncertainties in in situ measurements for the given measurement conditions, about 20 years after the fallout occurred, were found to be in the range 15-20% (with a coverage factor k=1, i.e. with a confidence interval of about 68%).

  • 11.
    Eriksson, David
    et al.
    Umeå University, Faculty of Medicine, Department of Clinical Microbiology, Immunology/Immunchemistry.
    Blomberg, Jeanette
    Umeå University, Faculty of Medicine, Department of Molecular Biology (Faculty of Medicine).
    Lindgren, Theres
    Umeå University, Faculty of Medicine, Department of Clinical Microbiology, Immunology/Immunchemistry.
    Löfroth, Per-Olov
    Umeå University, Faculty of Medicine, Department of Radiation Sciences, Radiation Physics.
    Johansson, Lennart
    Umeå University, Faculty of Medicine, Department of Radiation Sciences, Radiation Physics.
    Riklund, Katrine
    Umeå University, Faculty of Medicine, Department of Radiation Sciences, Diagnostic Radiology.
    Stigbrand, Torgny
    Umeå University, Faculty of Medicine, Department of Clinical Microbiology, Immunology/Immunchemistry.
    Iodine-131 induces mitotic catastrophes and activates apoptotic pathways in HeLa Hep2 cells2008In: Cancer Biotherapy and Radiopharmaceuticals, ISSN 1084-9785, E-ISSN 1557-8852, Vol. 23, no 5, p. 541-549Article in journal (Refereed)
    Abstract [en]

    Iodine-131 (131I) has been used both in unconjugated form and conjugated to antibody derivates (i.e., radioimmunotherapy; RIT) to treat malignant diseases. The mechanisms by which 131I-irradiation causes growth retardation are, however, inadequately understood. The aim of this study was to elucidate the sequential molecular and cellular events that initiate cell death in HeLa Hep2 cells exposed to 131I. In this paper, HeLa Hep2 cells were found to display a transient G2-M arrest following irradiation, but then reentered the cell cycle still containing unrepaired cellular damage. An increase of multipolar mitotic spindles, as well as a significant increase in centrosome numbers from 8.8% +/- 1.9% in controls to 54.7% +/- 2.2% in irradiated cells, was observed (p < 0.0001). A subsequent failure of cytokinesis caused the cells to progress into mitotic catastrophe. This was accompanied by the formation of giant cells with multiple nuclei, multilobulated nuclei, and an increased frequency of polyploidy cells. A fraction of the cells also displayed apoptotic features, including the activation of initiator caspases-2, -8, -9, and effector caspase-3, as well as cleavage of poly(ADP-ribose) polymerase, a cell-death substrate for active caspase-3. These findings demonstrate that mitotic catastrophes and the activation of a delayed type of apoptosis might be important mechanisms involved in cell death following the RIT of solid tumors with -emitting radionuclides, such as 131I.

  • 12.
    Eriksson, David
    et al.
    Umeå University, Faculty of Medicine, Department of Clinical Microbiology, Immunology/Immunchemistry.
    Löfroth, Per-Olov
    Umeå University, Faculty of Medicine, Department of Radiation Sciences, Radiation Physics.
    Johansson, Lennart
    Umeå University, Faculty of Medicine, Department of Radiation Sciences, Radiation Physics.
    Riklund, Katrine
    Umeå University, Faculty of Medicine, Department of Radiation Sciences, Diagnostic Radiology.
    Stigbrand, Torgny
    Umeå University, Faculty of Medicine, Department of Clinical Microbiology, Immunology/Immunchemistry.
    Apoptotic signalling in HeLa Hep2 cells following 5 Gy of cobalt-60 gamma radiation2009In: Anticancer Research, ISSN 0250-7005, E-ISSN 1791-7530, Vol. 29, no 11, p. 4361-4366Article in journal (Refereed)
    Abstract [en]

    BACKGROUND: The apoptotic signalling pathways involved in the delayed type of apoptosis occurring in HeLa Hep2 cells following radiation were investigated. MATERIALS AND METHODS: HeLa Hep2 cells were exposed to 5 Gy of cobalt-60 radiation. The activation of caspase-2, caspase-8, caspase-9 and effector caspase-3 was investigated by caspase assay plates and Western blots. Cleavage of poly (ADP-ribose) polymerase (PARP) was analysed on Western blots. HeLa Hep2 cells were irradiated with or without preincubation with inhibitors of protein synthesis (cycloheximide, CHX) and caspases, followed by TUNEL staining and caspase assay plate evaluation. RESULTS: Initiator caspases-2, -8, -9, and effector caspase-3, were found to be activated and PARP cleaved following irradiation. CHX completely inhibited the caspase activation and the associated apoptosis. Pretreatment with caspase-2 inhibitor indicated that caspase-2 was involved in the execution of the apoptosis. CONCLUSION: Activation of the apoptotic signalling pathways following irradiation of HeLa Hep2 cells includes components from the intrinsic as well as the extrinsic pathways and seems to require de novo protein synthesis.

  • 13.
    Eriksson, David
    et al.
    Umeå University, Faculty of Medicine, Clinical Microbiology, Immunology/Immunchemistry.
    Löfroth, Per-Olov
    Umeå University, Faculty of Medicine, Radiation Sciences, Radiation Physics.
    Johansson, Lennart
    Umeå University, Faculty of Medicine, Radiation Sciences, Radiation Physics.
    Åhlström Riklund, Katrine
    Umeå University, Faculty of Medicine, Radiation Sciences, Diagnostic Radiology.
    Stigbrand, Torgny
    Umeå University, Faculty of Medicine, Clinical Microbiology, Immunology/Immunchemistry.
    Cell cycle disturbances and mitotic catastrophes in HeLa Hep2 cells following 2.5 to 10 Gy of ionizing radiation.2007In: Clin Cancer Res, ISSN 1078-0432, Vol. 13, no 18 Pt 2, p. 5501s-5508sArticle in journal (Refereed)
    Abstract [en]

    PURPOSE: Experimental radioimmunotherapy delivering absorbed doses of 2.5 to 10 Gy has been shown to cause growth retardation of tumors. The purpose of this study was to elucidate the sequential molecular and cellular events occurring in HeLa Hep2 cells exposed to such doses. METHODS: Dose-response curves, activation of cell cycle checkpoints, and mitotic behavior were investigated in HeLa Hep2 cells following 2.5- to 10-Gy irradiation by carrying out 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide assays, Western blots, fluorescence-activated cell sorting analysis, and immunofluorescence stainings. Terminal deoxyribonucleotidyl transferase-mediated dUTP nick end labeling staining was used to detect apoptosis. RESULTS: A G2-M arrest was shown by fluorescence-activated cell sorting analysis. p53 and p21 were found to be up-regulated but were not immediately related to the arrest. The G2-M arrest was transient and the cells reentered the cell cycle still containing unrepaired cellular damage. This premature entry caused an increase of anaphase bridges, lagging chromosomal material, and multipolar mitotic spindles as visualized by propidium iodide staining and immunofluorescence staining with alpha-tubulin and gamma-tubulin antibodies. Furthermore, a dose-dependent significant increase in centrosome numbers from 12.6+/-6.6% to 67+/-5.3% was identified as well as a dose-dependent increase of polyploid cells from 2.8+/-1.3% to 17.6+/-2.1% with the highest absorbed dose of 10 Gy. These disturbances caused the cells to progress into mitotic catastrophe and a fraction of these dying cells showed apoptotic features as displayed by terminal deoxyribonucleotidyl transferase-mediated dUTP nick end labeling staining 5 to 7 days after irradiation. CONCLUSION: An absorbed dose of 2.5 to 10 Gy was shown to force HeLa Hep2 cells into mitotic catastrophe and delayed apoptosis. These might be important cell death mechanisms involved in tumor growth retardation following radioimmunotherapy of solid tumors.

  • 14.
    Eriksson, David
    et al.
    Umeå University, Faculty of Medicine, Clinical Microbiology.
    Mirzaie-Joniani, Homa
    Umeå University, Faculty of Medicine, Clinical Microbiology.
    Sheikholvaezin, Ali
    Umeå University, Faculty of Medicine, Clinical Microbiology.
    Löfroth, Per-Olov
    Umeå University, Faculty of Medicine, Radiation Sciences, Radiation Physics.
    Johansson, Lennart
    Umeå University, Faculty of Medicine, Radiation Sciences, Radiation Physics.
    Åhlström-Riklund, Katrine
    Umeå University, Faculty of Medicine, Radiation Sciences, Diagnostic Radiology.
    Stigbrand, Torgny
    Umeå University, Faculty of Medicine, Clinical Microbiology.
    Combined low dose radio- and radioimmunotherapy of experimental HeLa Hep 2 tumours.2003In: European Journal of Nuclear Medicine and Molecular Imaging, ISSN 1619-7070, E-ISSN 1619-7089, Vol. 30, no 6, p. 895-906Article in journal (Refereed)
    Abstract [en]

    Radiation therapy of malignant tumours can be delivered by external beam radiation (RT) or radioimmunotherapy (RIT), using nuclides attached to monoclonal antibodies (mAbs). These treatment modalities have now been combined in order to investigate putative therapeutic advantages and elucidate the biological responses involved. Nude mice were transplanted subcutaneously on the back with human HeLa Hep2 tumour cells. RT (3x5 Gy) and/or 100 microg (131)I-labelled mAb H7, against placental alkaline phosphatase, or (131)I-labelled mAb TS1, against cytokeratin, was administered separately or in combination (specific activity of 120-200 MBq/mg antibody). Significant tumour growth retardation was observed both with RT alone and with RIT alone. Combining these regimens enhanced the therapeutic effects further, and a significant reduction in tumour volume could be demonstrated. The tumours were subjected to extensive histochemical and immunohistochemical investigations in order to elucidate changes in biology and histology within them. The following stainings were used: haematoxylin-eosin (morphology), Ki67 (proliferation), M30 (apoptosis), TUNEL (apoptosis) and endoglin (vascularisation). Tumours in the control group grew fast, with an average tumour doubling time of 9 days. These tumours contained large viable tumour cell masses displaying vast proliferation zones of Ki67-positive tumour cells, as well as necrotic regions and small amounts of connective tissue. Apoptotic cells could be identified both with M30 and TUNEL staining. When RT was applied, the growth rate was significantly reduced (doubling time 19 days) and typical alterations in morphology were seen, with a relative increase in connective tissue and a decrease in necrotic regions. Apoptotic cells were identified and a decrease in cell density was also observed. When RIT alone was applied, the growth parameters indicated a longer lasting growth reduction, especially when TS1 was used separately or in combination with H7. The histological appearances of these tumours were somewhat different from the RT-treated tumours, with a larger portion of intratumoural cysts. These tumours also presented a reduced tumour cell density. Dramatic effects were observed when RT was combined with RIT, with a pronounced growth reduction seen in all combination treatment groups. Pronounced tumour volume reduction was also evident in both the RT + RIT ((131)I-TS1) group and RT + RIT ((131)I-TS1/(131)I-H7) group, and in some animals no tumour remained at all. The morphology of the tumour remnants at day 22 was chaotic with a drastically changed histology, with presence of abundant cysts, low fractions of Ki67-positive cells, reduction in cell density, increased amounts of connective tissue and a decrease in necrotic regions. Again, apoptotic cells could be identified, scattered throughout the viable regions. Combining RT and RIT seems to generate an efficient treatment with convincing and long-lasting tumour growth inhibition, which is reflected in a highly aberrant histology within the tumour. Results obtained in this study indicate that both necrosis and apoptosis may be involved in the process leading to this efficient therapy of epithelially derived tumours.

  • 15.
    Erlandsson, Ann
    et al.
    Umeå University, Faculty of Medicine, Clinical Microbiology.
    Eriksson, David
    Umeå University, Faculty of Medicine, Clinical Microbiology.
    Johansson, Lennart
    Umeå University, Faculty of Medicine, Radiation Sciences, Radiation Physics.
    Riklund, Katrine
    Umeå University, Faculty of Medicine, Radiation Sciences, Diagnostic Radiology.
    Stigbrand, Torgny
    Umeå University, Faculty of Medicine, Clinical Microbiology.
    Sundström, Birgitta Elisabeth
    In vivo clearing of idiotypic antibodies with antiidiotypic antibodies and their derivatives2006In: Molecular Immunology, ISSN 0161-5890, E-ISSN 1872-9142, Vol. 43, no 6, p. 599-606Article in journal (Refereed)
    Abstract [en]

    At immunolocalization of experimental tumors, idiotypic monoclonal antibodies, such as TS1 against cytokeratin 8, can be used to carry and deposit in vivo terapeutics in the tumor. These carriers also remain in the circulation and may cause negative side-effects in other tissues. In this report, several derivatives of the antiidiotypic antibody alphaTS1 were produced and tested for their clearing capacity of the idiotypic carrier antibody TS1. Intact monoclonal alphaTS1, scFv of a alphaTS1 and alphaTS1 Fab'2 and fragments were produced by recombinant technology or by cleavage with Ficin. The scFv was tailored by use of the variable domain genes of the light and heavy chain from the hybridoma clone in combination with a (Gly4Ser)3-linker, followed by expression in E. coli. When tested for clearing capacity, the intact divalent antiidiotypic IgG was found to be the most efficient. The divalent and the monovalent Fab fragment also demonstrated significant clearing, but lower than the intact antiidiotypic IgG. The alphaTS1 scFv antibody when injected separately was not found to clear the idiotype, but could do so when preincubated with the idiotype. Rapid excretion and in vivo instability of this low molecular weight antibody fragment may be the major reasons. Similar results were obtained when the system was reversed and the 131I-labeled antiidiotype IgG was cleared with the idiotype fragment. It is concluded that both intact antiidiotypic IgG, and Fab'2 fragments are able to clear the idiotypic antibodies. The experimental data support the conclusion that the Fc parts from both the idiotype and the antiidiotype may contribute to this elimination.

  • 16.
    Hedman, Angelica
    et al.
    Umeå University, Faculty of Medicine, Department of Radiation Sciences, Radiation Physics. Swedish Defence Research Agency, Division of CBRN Defence and Security, SE-90182 Umeå, Sweden.
    Gogani, J. Bahar
    Swedish Defence Research Agency, Division of CBRN Defence and Security, SE-90182 Umeå, Sweden.
    Granström, M.
    Swedish Defence Research Agency, Division of CBRN Defence and Security, SE-90182 Umeå, Sweden.
    Johansson, Lennart
    Umeå University, Faculty of Medicine, Department of Radiation Sciences, Radiation Physics.
    Andersson, Jonas S.
    Umeå University, Faculty of Medicine, Department of Radiation Sciences.
    Ramebäck, H.
    Swedish Defence Research Agency, Division of CBRN Defence and Security, SE-90182 Umeå, Sweden; Chalmers University of Technology, Department of Chemical and Biological Engineering, Nuclear Chemistry, SE-41296 Göteborg, Sweden.
    Characterization of HPGe detectors using Computed Tomography2015In: Nuclear Instruments and Methods in Physics Research Section A: Accelerators, Spectrometers, Detectors and Associated Equipment, ISSN 0168-9002, E-ISSN 1872-9576, Vol. 785, no 11 June 2015, p. 21-25Article in journal (Refereed)
    Abstract [en]

    Computed Tomography (CT) high resolution imaging have been used to investigate if there is a significant change in the crystal-to-window distance, i.e. the air gap thickness, in a small n-type detector cooled to 77 K, and in a medium sized p-type HPGe detector when cooled to 100 K. The findings were compared to detector dimension data made available by the manufacturer. The air gap thickness increased by (0.38 +/- 0.07) mm for the n-type detector and by (0.40 +/- 0.15) mm for the p-type detector when the detectors were cooled to 77 resp. 100 K compared to at room temperature. Monte Carlo calculations indicate that these differences have a significant impact on the efficiency in close geometries (< 5 cm). In the energy range of 40-700 keV with a source placed directly on endcap, the change in detector efficiency with temperature is 1.9-2.9% for the n-type detector and 0.3-2.1% for the p-type detector. The measured air gap thickness when cooling the detector was 1.1 mm thicker than manufacturer data for the n-type detector and 0.2 mm thicker for the p-type detector. In the energy range of 40-700 keV and with a source on endcap, this result in a change in detector efficiency of 5.2-7.1% for the n-type detector and 0.2-1.0% for the p-type detector, Le the detector efficiency is overestimated using data available by the manufacturer. (C) 2015 Elsevier B.V. All rights reserved.

  • 17.
    Häggström, Ida
    et al.
    Umeå University, Faculty of Medicine, Department of Radiation Sciences, Radiation Physics.
    Axelsson, Jan
    Umeå University, Faculty of Medicine, Department of Radiation Sciences, Radiation Physics.
    Schmidtlein, Ross
    Department of Medical Physics, Memorial Sloan Kettering Cancer Center, New York 10065, USA.
    Karlsson, Mikael
    Umeå University, Faculty of Medicine, Department of Radiation Sciences, Radiation Physics.
    Garpebring, Anders
    Umeå University, Faculty of Medicine, Department of Radiation Sciences, Radiation Physics.
    Johansson, Lennart
    Umeå University, Faculty of Medicine, Department of Radiation Sciences, Radiation Physics.
    Sörensen, Jens
    Medical Sciences, Nuclear Medicine, Uppsala University Hospital, Uppsala, Sweden.
    Larsson, Anne
    Umeå University, Faculty of Medicine, Department of Radiation Sciences, Radiation Physics.
    A Monte Carlo study of the dependence of early frame sampling on uncertainty and bias in pharmacokinetic parameters from dynamic PET2015In: Journal of Nuclear Medicine Technology, ISSN 0091-4916, E-ISSN 1535-5675, Vol. 43, no 1, p. 53-60Article in journal (Refereed)
    Abstract [en]

    Compartmental modeling of dynamic PET data enables quantifi- cation of tracer kinetics in vivo, through the calculated model parameters. In this study, we aimed to investigate the effect of early frame sampling and reconstruction method on pharmacokinetic parameters obtained from a 2-tissue model, in terms of bias and uncertainty (SD). Methods: The GATE Monte Carlo software was used to simulate 2 · 15 dynamic 3′-deoxy-3′-18F-fluorothymidine (18F-FLT) brain PET studies, typical in terms of noise level and kinetic parameters. The data were reconstructed by both 3- dimensional (3D) filtered backprojection with reprojection (3DRP) and 3D ordered-subset expectation maximization (OSEM) into 6 dynamic image sets with different early frame durations of 1, 2, 4, 6, 10, and 15 s. Bias and SD were evaluated for fitted parameter estimates, calculated from regions of interest. Results: The 2-tissue-model parameter estimates K1, k2, and fraction of arterial blood in tissue depended on early frame sampling, and a sampling of 6–15 s generally minimized bias and SD. The shortest sampling of 1 s yielded a 25% and 42% larger bias than the other schemes, for 3DRP and OSEM, respectively, and a parameter uncertainty that was 10%–70% higher. The schemes from 4 to 15 s were generally not significantly different in regards to bias and SD. Typically, the reconstruction method 3DRP yielded less framesampling dependence and less uncertain results, compared with OSEM, but was on average more biased. Conclusion: Of the 6 sampling schemes investigated in this study, an early frame duration of 6–15 s generally kept both bias and uncertainty to a minimum, for both 3DRP and OSEM reconstructions. Veryshort frames of 1 s should be avoided because they typically resulted in the largest parameter bias and uncertainty. Furthermore, 3DRP may be p

  • 18.
    Häggström, Ida
    et al.
    Umeå University, Faculty of Medicine, Department of Radiation Sciences, Radiation Physics.
    Johansson, Lennart
    Umeå University, Faculty of Medicine, Department of Radiation Sciences, Radiation Physics.
    Larsson, Anne
    Umeå University, Faculty of Medicine, Department of Radiation Sciences, Radiation Physics.
    Östlund, Nils
    Umeå University, Faculty of Medicine, Department of Radiation Sciences, Radiation Physics.
    Sörensen, Jens
    Medical Sciences, Nuclear Medicine, Uppsala University Hospital, Uppsala, Sweden.
    Karlsson, Mikael
    Umeå University, Faculty of Medicine, Department of Radiation Sciences, Radiation Physics.
    Semi-automatic tumour segmentation by selective navigation in a three-parameter volume, obtained by voxel-wise kinetic modelling of 11C-acetate2010In: Radiation Protection Dosimetry, ISSN 0144-8420, E-ISSN 1742-3406, Vol. 139, no 1-3, p. 214-218Article in journal (Refereed)
    Abstract [en]

    Positron emission tomography (PET) is increasingly used for delineation of tumour tissue in, for example, radiotherapy treatment planning. The most common method used is to outline volumes with a certain per cent uptake over background in a static image. However, PET data can also be collected dynamically and analysed by kinetic models, which potentially represent the underlying biology better. In the present study, a three-parameter kinetic model was used for voxel-wise evaluation of (11)C-acetate data of head/neck tumours. These parameters which represent the tumour blood volume, the uptake rate and the clearance rate of the tissue were derived for each voxel using a linear regression method and used for segmentation of active tumour tissue. This feasibility study shows that it is possible to segment images based on derived model parameters. There is, however, room for improvements concerning the PET data acquisition, noise reduction and the kinetic modelling. In conclusion, this early study indicates a strong potential of the method even though no 'true' tumour volume was available for validation.

  • 19.
    Häggström, Ida
    et al.
    Umeå University, Faculty of Medicine, Department of Radiation Sciences, Radiation Physics.
    Larsson, Anne
    Umeå University, Faculty of Medicine, Department of Radiation Sciences, Radiation Physics.
    Axelsson, Jan
    Umeå University, Faculty of Medicine, Department of Radiation Sciences, Radiation Physics.
    Garpebring, Anders
    Umeå University, Faculty of Medicine, Department of Radiation Sciences, Radiation Physics.
    Johansson, Lennart
    Umeå University, Faculty of Medicine, Department of Radiation Sciences, Radiation Physics.
    Schmidtlein, C. Ross
    Department of Medical Physics, Memorial Sloan Kettering Cancer Center, New York, USA.
    Sörensen, Jens
    Medical Sciences, Nuclear Medicine, Uppsala University Hospital, Uppsala, Sweden.
    Karlsson, Mikael
    Umeå University, Faculty of Medicine, Department of Radiation Sciences, Radiation Physics.
    The influence of time sampling scheme on kinetic parameters obtained from compartmental modeling of a dynamic PET study: a Monte Carlo study2012In: IEEE Nuclear Science Symposium Conference Record / [ed] B. Yu, Anaheim: IEEE conference proceedings, 2012, p. 3101-3107Conference paper (Refereed)
    Abstract [en]

    Compartmental modeling of dynamic PET data enables quantification of tracer kinetics in vivo, through the obtained model parameters. The dynamic data is sorted into frames during or after the acquisition, with a sampling interval usually ranging from 10 s to 300 s. In this study we wanted to investigate the effect of the chosen sampling interval on kinetic parameters obtained from a 2-tissue model, in terms of bias and standard deviation, using a complete Monte Carlo simulated dynamic F-18-FLT PET study. The results show that the bias and standard deviation in parameter K-1 is small regardless of sampling scheme or noise in the time-activity curves (TACs), and that the bias and standard deviation in k(4) is large for all cases. The bias in V-a is clearly dependent on sampling scheme, increasing for increased sampling interval. In general, a too short sampling interval results in very noisy images and a large bias of the parameter estimate, and a too long sampling interval also increases bias. Noise in the TACs is the largest source of bias.

  • 20.
    Jakobson Mo, Susanna
    et al.
    Umeå University, Faculty of Medicine, Department of Radiation Sciences, Diagnostic Radiology.
    Linder, Jan
    Umeå University, Faculty of Medicine, Department of Pharmacology and Clinical Neuroscience, Neurology.
    Forsgren, Lars
    Umeå University, Faculty of Medicine, Department of Pharmacology and Clinical Neuroscience, Neurology.
    Larsson, Anne
    Umeå University, Faculty of Medicine, Department of Radiation Sciences, Radiation Physics.
    Johansson, Lennart
    Umeå University, Faculty of Medicine, Department of Radiation Sciences, Radiation Physics.
    Riklund, Katrine
    Umeå University, Faculty of Medicine, Department of Radiation Sciences, Diagnostic Radiology.
    Pre- and postsynaptic dopamine SPECT in the early phase of idiopathic parkinsonism: a population-based study2010In: European Journal of Nuclear Medicine and Molecular Imaging, ISSN 1619-7070, E-ISSN 1619-7089, Vol. 37, no 11, p. 2154-2164Article in journal (Refereed)
    Abstract [en]

    PURPOSE: The aim of this study was to assess the diagnostic contribution of pre- and postsynaptic dopamine SPECT in drug-naïve patients with early idiopathic parkinsonism and to investigate possible differences between idiopathic Parkinson's disease (PD) and atypical parkinsonian syndromes (APS) and possible differences in motor subtypes of parkinsonism.

    METHODS: A group of 128 newly diagnosed idiopathic parkinsonian patients and 48 healthy controls was studied. Presynaptic baseline SPECT with (123)I-FP-CIT was performed in all patients and in 120 patients also a baseline postsynaptic SPECT with (123)I-IBZM. Clinical diagnoses were reassessed after 12 months.

    RESULTS: Presynaptic uptake in the putamen and caudate was significantly reduced in patients compared to controls. Presynaptic uptake ratios were not different between PD patients and patients with APS, and postsynaptic uptake in APS was not significantly reduced compared to PD or controls. In half of the APS patients both pre- and postsynaptic uptake ratios were reduced on the same side in the striatum. Impaired motor performance was associated with decreased presynaptic uptake in the putamen in PD. The postural instability and gait difficulty (PIGD) subtype of PD had lower presynaptic uptake ratios than patients with tremor-dominated (TD) symptoms.

    CONCLUSION: Not only presynaptic putamen uptake ratios, but also caudate ratios were reduced in a majority of the patients in our study. At baseline scan, i.e. in an early stage of the disease, the accuracy of excluding APS in the whole study population was 85% using a combination of pre- and postsynaptic SPECT. Already at baseline, lower presynaptic SPECT ratios were seen in PD with PIGD at onset compared to those with TD subtype.

  • 21.
    Johansson, Amanda
    et al.
    Umeå University, Faculty of Medicine, Clinical Microbiology, Immunology/Immunchemistry.
    Eriksson, David
    Umeå University, Faculty of Medicine, Clinical Microbiology, Immunology/Immunchemistry.
    Ullen, Anders
    Umeå University, Faculty of Medicine, Clinical Microbiology, Immunology/Immunchemistry.
    Löfroth, Per-Olov
    Umeå University, Faculty of Medicine, Radiation Sciences, Radiation Physics.
    Johansson, Lennart
    Umeå University, Faculty of Medicine, Radiation Sciences, Radiation Physics.
    Åhlström-Riklund, Katrine
    Umeå University, Faculty of Medicine, Radiation Sciences, Diagnostic Radiology.
    Stigbrand, Torgny
    Umeå University, Faculty of Medicine, Clinical Microbiology, Immunology/Immunchemistry.
    The combination of external beam radiotherapy and experimental radioimmunotargeting with a monoclonal anticytokeratin antibody2002In: Cancer, ISSN 0008-543X, E-ISSN 1097-0142, Vol. 94, no S4, p. 1314-1319Article in journal (Refereed)
  • 22. Johansson, Amanda
    et al.
    Sandström, Per
    Ullén, Anders
    Erlandsson, Ann
    Sundström, Birgitta
    Riklund, Katrine
    Umeå University, Faculty of Medicine, Department of Radiation Sciences, Diagnostic Radiology.
    Johansson, Lennart
    Umeå University, Faculty of Medicine, Department of Radiation Sciences, Radiation Physics.
    Hietala, Sven-Ola
    Umeå University, Faculty of Medicine, Department of Radiation Sciences, Diagnostic Radiology.
    Stigbrand, Torgny
    Umeå University, Faculty of Medicine, Department of Clinical Microbiology, Immunology/Immunchemistry.
    Stability and immunoreactivity of the monoclonal anticytokeratin antibody TS1 after different degrees of iodination.1999In: Acta Oncologica, ISSN 0284-186X, E-ISSN 1651-226X, Vol. 38, no 3, p. 329-334Article in journal (Refereed)
    Abstract [en]

    The immunoreactivity, stability and in vivo kinetics of an anticytokeratin 8 monoclonal antibody, TS1, were investigated following different degrees of labeling with 125I (0.2, 1 and 2-3 125I/TS1 MAb). By testing with ELISA, it was demonstrated that a high degree of iodination, i.e. > 2 125I/TS1, caused a rapid decrease in immunoreactivity to almost zero within 10 days. Furthermore, a complete degradation to low molecular weight fragments and free iodine was seen, as shown by SDS PAGE and autoradiography. The differently labeled radionuclide conjugates were injected into nude mice inoculated with HeLa Hep2 cells and tumor doses (estimated by MIRD formalism), tumor:non-tumor dose ratios, % I.D./gram tissue, Gy/MBq and in vivo kinetics of the differently labeled MAbs were determined. Despite the in vitro instability of the highest iodinated radionuclide conjugate, it was possible to deliver high doses to the tumors if the conjugate was injected into the animal immediately after completion of the iodination procedure. Increases from 1.4 Gy to 15.2 Gy delivered tumor dose were obtained with a tenfold increase in the specific activity, without alterations in the tumor:non-tumor tissue dose ratios. There is room for significant improvements in efficacy at radioimmunotherapy, which can be gained by optimizing the degree of iodination. For therapeutical applications a high degree of iodination may be an advantage.

  • 23.
    Johansson, Erik
    et al.
    Umeå University, Faculty of Medicine, Department of Radiation Sciences, Radiation Physics.
    Andersson, Jonas
    Umeå University, Faculty of Medicine, Department of Radiation Sciences, Radiation Physics.
    Johansson, Lennart
    Umeå University, Faculty of Medicine, Department of Radiation Sciences, Radiation Physics.
    Tölli, Heikki
    Umeå University, Faculty of Medicine, Department of Radiation Sciences, Radiation Physics.
    Liquid ionization chamber initial recombination dependence on LET for electrons and photons2013In: Physics in Medicine and Biology, ISSN 0031-9155, E-ISSN 1361-6560, Vol. 58, no 12, p. 4225-4236Article in journal (Refereed)
    Abstract [en]

    The possibility of indirect measurements of linear energy transfer (LET) with a liquid ionization chamber (LIC) has been investigated by studying initial recombination losses at different applied voltages. A linear fit is made to the voltage-signal curve and the intersection point of the fit and the voltage-axis is shown to correlate with LET. The LIC applied voltages were 100-700 V, which corresponds to electric field strengths between 0.3 and 2.0 MV m(-1). Several different photon and electron beams have been studied, and by using MCNPX (TM) the respective LET spectra have been determined. The beam qualities in this study were found to have a fluence averaged LET between 0.17 and 1.67 keV mu m(-1) and a corresponding dose averaged LET between 0.97 and 4.62 keV mu m(-1). For the experimental data in this study the linear fit method yields consistent results with respect to Monte Carlo simulated LET values. A calibration curve for LET determination is provided for the LIC used in the present work.

  • 24.
    Larsson, Anne
    et al.
    Umeå University, Faculty of Medicine, Department of Radiation Sciences, Radiation Physics.
    Johansson, Lennart
    Umeå University, Faculty of Medicine, Department of Radiation Sciences, Radiation Physics.
    Scatter-to-primary based scatter fractions for transmission dependent convolution subtraction of SPECT images2003In: Physics in Medicine and Biology, ISSN 0031-9155, E-ISSN 1361-6560, Vol. 48, no 22, p. N323-N328Article in journal (Refereed)
    Abstract [en]

    In single photon emission computed tomography (SPECT), transmission-dependent convolution subtraction has been shown to be useful when correcting for scattered events. The method is based on convolution subtraction, but includes a matrix of scatter fractions instead of a global scatter fraction. The method can be extended to iteratively improve the scatter estimate, but in this note we show that this requires a modification of the theory to use scatter-to-total scatter fractions for the first iteration only and scatter-to-primary fractions thereafter. To demonstrate this, scatter correction is performed on a Monte Carlo simulated image of a point source of activity in water. The modification of the theory is compared to corrections where the scatter fractions are based on the scatter-to-total ratio, using one and ten iterations. The resulting ratios of subtracted to original counts are compared to the true scatter-to-total ratio of the simulation and the most accurate result is found for our modification of the theory.

  • 25.
    Larsson, Anne
    et al.
    Umeå University, Faculty of Medicine, Department of Radiation Sciences, Radiation Physics.
    Johansson, Lennart
    Umeå University, Faculty of Medicine, Department of Radiation Sciences, Radiation Physics.
    Transmission-dependent convolution subtraction of 99m-Tc-HMPAO rCBF SPECT - a Monte Carlo study2005In: IEEE Transactions on Nuclear Science, ISSN 0018-9499, E-ISSN 1558-1578, Vol. 52, no 1, p. 231-237Article in journal (Refereed)
    Abstract [en]

    Transmission-dependent convolution subtraction has been shown to be useful when correcting for malpositioned scattered events in single photon emission computed tomography (SPECT). The method is based on convolution subtraction but includes a matrix of scatter fractions instead of a global scatter fraction. In this study, this method is evaluated for regional cerebral blood flow SPECT with 99mTc-hexamethyl propylene-amine oxime (HMPAO) by using Monte Carlo simulations. Different geometries for generating the scatter fractions as a function of the attenuation path length are studied and compared. The most optimal value of the exponential describing the falloff of the monoexponential scatter kernel is determined for each geometry. The method is also compared with convolution subtraction with a global scatter fraction. It is shown that the most optimal of the tested geometries is a homogeneous activity distribution. A scatter kernel with an exponential of 0.15 pixel-1 is most optimal for this geometry. A comparison with convolution subtraction shows that transmission-dependent convolution subtraction can give more accurate results if used with optimal parameters.

  • 26.
    Larsson, Anne
    et al.
    Umeå University, Faculty of Medicine, Department of Radiation Sciences, Radiation Physics.
    Johansson, Lennart
    Umeå University, Faculty of Medicine, Department of Radiation Sciences, Radiation Physics.
    Rossi Norrlund, Rauni
    Umeå University, Faculty of Medicine, Department of Radiation Sciences, Diagnostic Radiology.
    Riklund Åhlström, Katrine
    Umeå University, Faculty of Medicine, Department of Radiation Sciences, Diagnostic Radiology.
    Methods for estimating uptake and absorbed dose in tumours from I-125 labelled monoclonal antibodies, based on scintigraphic imaging of mice.1999In: Acta Oncologica, ISSN 0284-186X, E-ISSN 1651-226X, Vol. 38, no 3, p. 361-365Article in journal (Refereed)
    Abstract [en]

    Monoclonal antibodies for radioimmunotargeting are often tested in tumour bearing nude mice. In vivo determination of the uptake of the monoclonal antibody in the tumour requires quantitative scintigraphy, and this in turn requires an adequate method for subtraction of radiation from the normal tissue. For this reason, two different methods for background subtraction were evaluated, a contralateral background region of interest or an irregular one, surrounding the tumour. A pinhole collimator was used for the scintigraphy and the monoclonal antibodies were labelled with 125I. Furthermore, a method was developed for estimation of the mean absorbed dose in the tumour from these repeated quantitative scintigraphic measurements. This requires that the tumour mass can be accurately estimated in vivo. Finally, the results were compared with in vitro measurements of the uptake.

  • 27.
    Larsson, Anne
    et al.
    Umeå University, Faculty of Medicine, Radiation Sciences, Radiation Physics.
    Johansson, Lennart
    Umeå University, Faculty of Medicine, Radiation Sciences, Radiation Physics.
    Sundström, Torbjörn
    Umeå University, Faculty of Medicine, Radiation Sciences, Diagnostic Radiology.
    Riklund Åhlström, Katrine
    Umeå University, Faculty of Medicine, Radiation Sciences, Diagnostic Radiology.
    A method for attenuation and scatter correction of brain SPECT based on computed tomography images2003In: Nuclear medicine communications, ISSN 0143-3636, E-ISSN 1473-5628, Vol. 24, no 4, p. 411-420Article in journal (Refereed)
    Abstract [en]

    A method for attenuation and scatter correction of brain single photon emission computed tomography (SPECT) is described where computed tomography (CT) images of the brain are used for the calculation of attenuation maps. The method is evaluated for the substance 99mTc hexamethylpropylene amine oxime. A transmission dependent scatter correction is utilized and is based on ray sums calculated through the attenuation map. A method based on external markers is used to align the SPECT and CT image volumes. The markers need only to be present during the SPECT acquisition since the corresponding landmarks can be found without markers on the CT images. The mismatching has been investigated for five patients who have undergone both a CT examination and a SPECT examination with markers. Twelve individuals from the staff have pointed out the landmarks on the CT images, with an average standard deviation of 3.4 mm. Reconstructions with an attenuation map shifted the corresponding 95% confidence interval have been performed to obtain an estimation of the quantitative uncertainty caused by the mismatching, and quantitative errors of up to 6.3% have been measured. At present the method is probably most useful when groups of patients are studied.

  • 28. Leide-Svegborn, Sigrid
    et al.
    Ahlgren, Lars
    Johansson, Lennart
    Umeå University, Faculty of Medicine, Department of Radiation Sciences.
    Mattsson, Sören
    Excretion of radionuclides in human breast milk after nuclear medicine examinations. Biokinetic and dosimetric data and recommendations on breastfeeding interruption2016In: European Journal of Nuclear Medicine and Molecular Imaging, ISSN 1619-7070, E-ISSN 1619-7089, Vol. 43, no 5, p. 808-821Article in journal (Refereed)
    Abstract [en]

    Purpose To review early recommendations and propose guidelines for breastfeeding interruption after administration of radiopharmaceuticals, based on additional biokinetic and dosimetric data.

    Methods Activity concentrations in breast milk from 53 breastfeeding patients were determined. The milk was collected at various times after administration of 16 different radiopharmaceuticals. The fraction of the activity administered to the mother excreted in the breast milk, the absorbed doses to various organs and tissues and the effective dose to the infant were estimated.

    Results The fraction of the administered activity excreted per millilitre of milk varied widely from 10(-10) to 10(-3) MBq/MBq administered. For Tc-99m-labelled radiopharmaceuticals, the total fraction of the administered activity excreted in the milk varied from 0.0057 % for Tc-99m-labelled red blood cells (RBC) to 19 % for Tc-99m-pertechnetate. The effective dose to an infant per unit activity administered to the mother ranged from 6.7 x 10(-6) mSv/MBq for Tc-99m-labelled RBC to 3.6 x 10(-2) mSv/MBq for Tc-99m-pertechnetate. For the other radiopharmaceuticals, the total fraction of administered activity excreted in the milk varied from 0.018 % (Cr-51-EDTA) to 48 % (I-131-NaI). The effective dose ranged from 5.6 x 10(-5) mSv(infant)/MBq(mother) (Cr-51-EDTA) to 106 mSv(infant)/MBq(mother) (I-131-NaI).

    Conclusions Based on an effective dose limit of 1 mSv to the infant and a typical administered activity, we recommend cessation of breastfeeding for I-131-NaI and interruption of feeding for 12 h for I-125-iodohippurate, I-131-iodohippurate, Tc-99m-pertechnetate and Tc-99m-MAA. During this 12-h period all breast milk should be expressed at least three times and discarded. For the other radiopharmaceuticals included in this study, no interruption of breastfeeding is necessary.

  • 29.
    Lindgren, Theres
    et al.
    Umeå University, Faculty of Medicine, Department of Clinical Microbiology, Immunology/Immunchemistry.
    Johansson, Lennart
    Umeå University, Faculty of Medicine, Department of Radiation Sciences, Radiation Physics.
    Riklund, Katrine
    Umeå University, Faculty of Medicine, Department of Radiation Sciences, Diagnostic Radiology.
    Stigbrand, Torgny
    Umeå University, Faculty of Medicine, Department of Clinical Microbiology, Immunology/Immunchemistry.
    Erikssom, David
    Umeå University, Faculty of Medicine, Department of Clinical Microbiology, Immunology/Immunchemistry.
    Alterations in gene expression during radiation induced mitotic catastrophe in HeLa Hep2 cellsManuscript (preprint) (Other academic)
    Abstract [en]

    Purpose: To explore kinetic changes in the gene expression profile during radiation induced mitotic catastrophes.

    Methods and Materials: We measured temporal global gene expression in HeLa Hep2 tumor cells using bead chip arrays (Illumina) following exposure to 5 Gy of ionizing radiation (60Co). Genes with less than a 2-fold change in expression and a p-value > 0.05 were discarded. Signaling pathways significantly altered following irradiation were explored using Metacore. Furthermore, biological responses linked to mitotic catastrophe including cell cycle arrests, anaphase bridge formation and centrosome amplification were analyzed and correlation to gene expression changes evaluated.

    Results: Following irradiation a G2-arrest was induced. This arrest was transient and cells entered mitosis before DNA damage was repaired causing anaphase bridge formation. Furthermore, radiation induced hyperamplification of centrosomes was observed. These phenotypical changes correlated well with the observed gene expression changes. At 6 h following irradiation the expression was changed only for a few genes including histone H2 and H4, essential for activation of a DNA-damage checkpoint. Striking changes appeared at later time-points. From 12-96 hours post irradiation a significant fraction of the genes with altered expression were found to be involved in cell cycle progression and its regulation. The significant changes were seen for genes important for several mitotic processes, and those involved in the G2- and spindle assembly checkpoints. Also centrosome associated genes displayed an increased expression. Furthermore, 96 hours after irradiation pathways involved in immune and inflammatory responses were significantly altered.

    Conclusions: This study elucidates specific characteristics in the altered gene expression pattern induced by irradiation, which can be linked to the sequential steps observed in HeLa Hep2 cells during mitotic catastrophes. Therapeutic strategies employing these alterations might potentiate future therapy and enhance tumor cell killing.

  • 30.
    Lindgren, Theres
    et al.
    Umeå University, Faculty of Medicine, Department of Clinical Microbiology, Clinical Immunology.
    Stigbrand, Torgny
    Umeå University, Faculty of Medicine, Department of Clinical Microbiology, Clinical Immunology.
    Johansson, Lennart
    Umeå University, Faculty of Medicine, Department of Radiation Sciences, Radiation Physics.
    Riklund, Katrine
    Umeå University, Faculty of Medicine, Department of Radiation Sciences, Diagnostic Radiology.
    Eriksson, David
    Umeå University, Faculty of Medicine, Department of Clinical Microbiology, Clinical Immunology.
    Alterations in Gene Expression During Radiation-Induced Mitotic Catastrophe in He La Hep2 Cells2014In: Anticancer Research, ISSN 0250-7005, E-ISSN 1791-7530, Vol. 34, no 8, p. 3875-3880Article in journal (Refereed)
    Abstract [en]

    Aim: To explore kinetic changes in the gene expression profile during radiation-induced mitotic catastrophes. Materials and Methods: Gene expression changes were measured in HPV-infected HeLa Hep2 tumor cells following exposure to 5 Gy of ionizing radiation (Co-60). Signaling pathways were explored and correlated to the biological responses linked to mitotic catastrophe. Results: Following irradiation a transient G(2)-arrest was induced. Anaphase bridge formation and centrosome hyperamplification was observed. These phenotypical changes correlated well with the observed gene expression changes. Genes with altered expression were found to be involved in mitotic processes as well as G(2)- and spindle assembly checkpoints. Also centrosome-associated genes displayed an increased expression. Conclusion: This study elucidates specific characteristics in the altered gene expression pattern induced by irradiation, which can be correlated to the events of mitotic catastrophe in HeLa Hep2 cells. Therapeutic strategies modulating these alterations might potentiate future therapy and enhance tumor cell killing.

  • 31.
    Lindgren, Theres
    et al.
    Umeå University, Faculty of Medicine, Department of Clinical Microbiology, Immunology/Immunchemistry.
    Stigbrand, Torgny
    Umeå University, Faculty of Medicine, Department of Clinical Microbiology, Immunology/Immunchemistry.
    Raberg, A
    Riklund, Katrine
    Umeå University, Faculty of Medicine, Department of Radiation Sciences, Diagnostic Radiology.
    Johansson, Lennart
    Umeå University, Faculty of Medicine, Department of Radiation Sciences, Radiation Physics.
    Eriksson, David
    Genome wide expression analysis of radiation induced DNA damage responses in isogenic HCT 116 cell lines2012In: Tumor Biology, ISSN 1010-4283, E-ISSN 1423-0380, Vol. 33, no Suppl. 1, p. 76-76Article in journal (Other academic)
  • 32.
    Lindgren, Theres
    et al.
    Umeå University, Faculty of Medicine, Department of Clinical Microbiology, Immunology/Immunchemistry.
    Stigbrand, Torgny
    Umeå University, Faculty of Medicine, Department of Clinical Microbiology, Immunology/Immunchemistry.
    Riklund, Katrine
    Umeå University, Faculty of Medicine, Department of Radiation Sciences, Diagnostic Radiology.
    Johansson, Lennart
    Umeå University, Faculty of Medicine, Department of Radiation Sciences, Radiation Physics.
    Eriksson, David
    Umeå University, Faculty of Medicine, Department of Clinical Microbiology, Immunology/Immunchemistry.
    Gene expression profiling in MOLT-4 cells during gamma-radiation-induced apoptosis2012In: Tumor Biology, ISSN 1010-4283, E-ISSN 1423-0380, Vol. 33, no 3, p. 689-700Article in journal (Refereed)
    Abstract [en]

    This study aims to identify the temporal changes in gene expression in MOLT-4, a leukemia cell line, in response to radiation and to present a comprehensive description of the pathways and processes that most significantly relate to the cellular biological responses. A global gene expression profile of 24,500 genes was performed on MOLT-4 tumor cells following exposure to 5 Gy of ionizing radiation (Co-60) using a bead chip array (Illumina). Signaling pathways and processes significantly altered following irradiation were explored using MetaCore. Cellular viability [3-(4,5 dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide], activation of cell cycle checkpoints [fluorescence activated cell sorting (FACS)], and induction of apoptosis (FACS, caspase assays) were evaluated to correlate these biological responses to the gene expression changes. Totally, 698 different genes displayed a significantly altered expression following radiation, and out of these transcripts, all but one showed increased expression. One hour following irradiation, the expression was changed only for a few genes. Striking changes appeared at later time-points. From 3 to 24 h post-irradiation, a significant fraction of the genes with altered expression were found to be involved in cell cycle checkpoints and their regulation (CDKN1A), DNA repair (GADD45A, DDB2, XPC), apoptosis induction (DR5, FasR, Apo-2L, Bax), and T-cell activation/proliferation (CD70, OX40L). Irradiated MOLT-4 cells were arrested at the G2-checkpoint, followed by a decrease in cell viability, most pronounced 48 h after exposure. The cell death was executed by induced apoptosis and was visualized by an increase in subG1 cells and an increased activation of initiator (caspase-8 and caspase-9) and execution (caspase-3) caspases. Activation of cell cycle arrest and apoptosis correlated well in time with the changes in gene expression of those genes important for these biological processes. Activation of the apoptotic signaling pathways in MOLT-4 cells following irradiation includes components from the intrinsic as well as the extrinsic apoptotic pathways. This study indicates that the altered gene expression pattern induced by irradiation is important for the sequential steps observed in MOLT-4 cells during apoptosis induction.

  • 33.
    Lindgren, Theres
    et al.
    Umeå University, Faculty of Medicine, Department of Clinical Microbiology, Immunology/Immunchemistry.
    Stigbrand, Torgny
    Umeå University, Faculty of Medicine, Department of Clinical Microbiology, Immunology/Immunchemistry.
    Råberg, Aino
    Umeå University, Faculty of Medicine, Department of Clinical Microbiology, Immunology/Immunchemistry.
    Riklund, Katrine
    Umeå University, Faculty of Medicine, Department of Radiation Sciences, Diagnostic Radiology.
    Johansson, Lennart
    Umeå University, Faculty of Medicine, Department of Radiation Sciences, Radiation Physics.
    Eriksson, David
    Umeå University, Faculty of Medicine, Department of Clinical Microbiology, Immunology/Immunchemistry.
    Genome wide expression analysis of radiation induced DNA damage responses in isogenic HCT116 p53 +/+ and HCT116 p53 -/- colorectal carcinoma cell lines2015In: International Journal of Radiation Biology, ISSN 0955-3002, E-ISSN 1362-3095, Vol. 91, no 1, p. 99-111Article in journal (Refereed)
    Abstract [en]

    Purpose : To study the kinetics of gene expression alterations following radiation exposure of isogenic HCT116 p53+/+ and HCT116 p53-/- cell lines. Materials and methods : Cells were exposed to 5 Gy of irradiation (Cs-137) and genome-wide temporal expression analysis using Illumina bead chip arrays was performed. Signalling pathways were explored using Metacore (Genego). Biological responses including cell cycle checkpoint activation, centrosome amplification and senescence induction were analyzed. Results : Significant differences in the radiation response were observed between the p53+/+ and the p53-/- cell lines. In p53+/+ cells concurrent G1- and G2-arrests were activated followed by senescence induction. Increased expression of genes associated with senescence, senescence associated secretory phenotype (SASP) and repression of genes essential for G2-M transition were detected. P53-/- cells arrested mainly in G2 followed by centrosome amplification, mitotic slippage and a subsequent increase of polyploid cells. Furthermore, changes in expression correlated well with these signs of mitotic catastrophe. Conclusions : The presence or absence of p53 triggers different signalling cascades with different endpoints. Elucidating these differences is important as it enables improvement of radiation treatment and could be used to develop new combination treatments with specific inhibitors of key regulators of these cell death modalities.

  • 34.
    Lizana, Helena
    et al.
    Umeå University, Faculty of Medicine, Department of Radiation Sciences, Radiation Physics.
    Johansson, Lennart
    Umeå University, Faculty of Medicine, Department of Radiation Sciences, Radiation Physics.
    Axelsson, Jan
    Umeå University, Faculty of Medicine, Department of Radiation Sciences, Radiation Physics.
    Larsson, Anne
    Umeå University, Faculty of Medicine, Department of Radiation Sciences, Radiation Physics.
    Ögren, Mattias
    Umeå University, Faculty of Medicine, Department of Radiation Sciences, Diagnostic Radiology.
    Linder, Jan
    Umeå University, Faculty of Medicine, Department of Pharmacology and Clinical Neuroscience, Clinical Neuroscience.
    Halldin, Christer
    Varrone, Andrea
    Jakobson Mo, Susanna
    Umeå University, Faculty of Medicine, Department of Radiation Sciences, Diagnostic Radiology.
    Whole-Body Biodistribution and Dosimetry of the Dopamine Transporter Radioligand 18F-FE-PE2I in Human Subjects2018In: Journal of Nuclear Medicine, ISSN 0161-5505, E-ISSN 1535-5667, Vol. 59, no 8, p. 1275-1280Article in journal (Refereed)
    Abstract [en]

    F-18-(E)-N-(3-iodoprop-2-enyl)-2 beta-carbofluoroethoxy-3 beta-(4'-methylphenyl) nortropane (F-18-FE-PE2I) was recently developed and has shown adequate affinity and high selectivity for the dopamine transporter (DAT). Previous studies have shown promising results for F-18-FE-PE2I as a suitable radioligand for DAT imaging. In this study, we investigated the whole-body biodistribution and dosimetry of F-18-FE-PE2I in healthy volunteers to support its utility as a suitable PET imaging agent for the DAT. Methods: Five healthy volunteers were given a mean activity of 2.5 MBq/kg, and 3 PET scans, head to thigh, were performed immediately after injection followed by 4 whole-body PET/CT scans between 0.5 and 6 h after injection. Blood samples were drawn in connection with the whole-body scans, and all urine was collected until 6 h after injection. Volumes of interest were delineated around 17 organs on all images, and the areas under the time-activity curves were calculated to obtain the total number of decays in the organs. The absorbed doses to organs and the effective dose were calculated using the software IDAC. Results: The highest activity concentration was observed in the liver (0.9%-1.2% injected activity/100 g) up to 30 min after injection. At later time points, the highest concentration was seen in the gallbladder (1.1%-0.1% injected activity/100 g). The activity excreted with urine ranged between 23% and 34%, with a mean of 28%. The urinary bladder received the highest absorbed dose (119 mu Gy/MBq), followed by the liver (46 mu Gy/MBq). The effective dose was 23 mu Sv/MBq (range, 19-28 mu Sv/MBq), resulting in an effective dose of 4.6 mSv for an administered activity of 200 MBq. Conclusion: The effective dose is within the same order of magnitude as other commonly used PET imaging agents as well as DAT agents. The reasonable effective dose, together with the previously reported favorable characteristics for DAT imaging and quantification, indicates that F-18-FE-PE2I is a suitable radioligand for DAT imaging.

  • 35. Ljungberg, Michael
    et al.
    Larsson, Anne
    Umeå University, Faculty of Medicine, Department of Radiation Sciences, Radiation Physics.
    Johansson, Lennart
    Umeå University, Faculty of Medicine, Department of Radiation Sciences, Radiation Physics.
    A new collimator simulation in SIMIND based on the delta-scattering technique2005In: IEEE Transactions on Nuclear Science, ISSN 0018-9499, E-ISSN 1558-1578, Vol. 52, no 5, p. 1370-1375Article in journal (Refereed)
    Abstract [en]

    To use conventional ray tracing methods in Monte Carlo simulation of the collimator in a scintillation camera system can be time consuming. It is however necessary to take collimator interactions into account when simulating radionuclides emitting high-energy photons that can penetrate the septa in the collimator. In this work a statistical collimator algorithm, based on the Delta-Scattering method, is evaluated using 123I. The evaluation is performed by comparing results from Monte Carlo simulations and measurements for a scintillation camera system, using point sources and a nonhomogeneous brain phantom. A good agreement can be seen for both images and energy spectra.

  • 36. Mattsson, Sören
    et al.
    Johansson, Lennart
    Umeå University, Faculty of Medicine, Department of Radiation Sciences, Radiation Physics.
    Liniecki, J
    Nosske, D
    Stabin, M
    Leide-Svegborn, S
    Taylor, D
    Radiation dose to patients from radiopharmaceuticals2009In: IFMBE Proceedings 25/III / [ed] O Dössel, W C Schlegel, R Magjarevic, Springer Verlag , 2009, p. 474-477Chapter in book (Refereed)
  • 37. Mattsson, Sören
    et al.
    Johansson, Lennart
    Umeå University, Faculty of Medicine, Department of Radiation Sciences, Radiation Physics.
    Liniecki, J
    Nosske, D
    Stabin, M
    Leide-Svegborn, S
    Taylor, D
    Radiation dose to patients from radiopharmaceuticals2009In: World Congress on Medical Physics and Biomedical Engineering, September 7 - 12, 2009, Munich, Germany: Vol. 25/3 Radiation Protection and Dosimetry, Biological Effects of Radiation, Berlin: Springer , 2009, p. 474-477Conference paper (Refereed)
    Abstract [en]

    A Task Group within ICRP Committee 2 and 3 is continuously working to improve absorbed dose estimates to patients investigated with radiopharmaceuticals. The work deals with reviews of the literature, the initiation of new studies - and often to carry them out in-house. Dose calculations have up to now been done using the MIRD formalism. Recently, a new addendum to ICRP Publication 53 has been published under the name of ICRP Publication 106. This paper present the ongoing work within the Task Group.

  • 38. Mirzaie-Joniani, Homa
    et al.
    Eriksson, David
    Umeå University, Faculty of Medicine, Department of Clinical Microbiology.
    Johansson, Amanda
    Löfroth, Per-Olov
    Umeå University, Faculty of Medicine, Department of Radiation Sciences, Radiation Physics.
    Johansson, Lennart
    Umeå University, Faculty of Medicine, Department of Radiation Sciences, Radiation Physics.
    Åhlström-Riklund, Katrine
    Umeå University, Faculty of Medicine, Department of Radiation Sciences, Diagnostic Radiology.
    Stigbrand, Torgny
    Umeå University, Faculty of Medicine, Department of Clinical Microbiology, Immunology/Immunchemistry.
    Apoptosis in HeLa Hep2 cells is induced by low-dose, low-dose-rate radiation.2002In: Radiation Research, ISSN 0033-7587, E-ISSN 1938-5404, Vol. 158, no 5, p. 634-640Article in journal (Refereed)
  • 39.
    Mu, Xiangkui
    et al.
    Umeå University, Faculty of Medicine, Department of Radiation Sciences, Oncology.
    Björk-Eriksson, Thomas
    Nill, Simeon
    Oelfke, Uwe
    Johansson, Karl-Axel
    Gagliardi, Giovanna
    Johansson, Lennart
    Umeå University, Faculty of Medicine, Department of Radiation Sciences, Radiation Physics.
    Karlsson, Mikael
    Umeå University, Faculty of Medicine, Department of Radiation Sciences, Radiation Physics.
    Zackrisson, Björn
    Umeå University, Faculty of Medicine, Department of Radiation Sciences, Oncology.
    Does electron and proton therapy reduce the risk of radiation induced cancer after spinal irradiation for childhood medulloblastoma? A comparative treatment planning study2005In: Acta Oncologica, ISSN 0284-186X, E-ISSN 1651-226X, Vol. 44, no 6, p. 554-562Article in journal (Refereed)
    Abstract [en]

    The aim of this treatment planning comparison study was to explore different spinal irradiation techniques with respect to the risk of late side-effects, particularly radiation-induced cancer. The radiotherapy techniques compared were conventional photon therapy, intensity modulated x-ray therapy (IMXT), conventional electron therapy, intensity/energy modulated electron therapy (IMET) and proton therapy (IMPT).CT images for radiotherapy use from five children, median age 8 and diagnosed with medulloblastoma, were selected for this study. Target volumes and organs at risk were defined in 3-D. Treatment plans using conventional photon therapy, IMXT, conventional electron therapy, IMET and IMPT were set up. The probability of normal tissue complication (NTCP) and the risk of cancer induction were calculated using models with parameters-sets taken from published data for the general population; dose data were taken from dose volume histograms (DVH). Similar dose distributions in the targets were achieved with all techniques but the absorbed doses in the organs-at-risk varied significantly between the different techniques. The NTCP models based on available data predicted very low probabilities for side-effects in all cases. However, the effective mean doses outside the target volumes, and thus the predicted risk of cancer induction, varied significantly between the techniques. The highest lifetime risk of secondary cancers was estimated for IMXT (30%). The lowest risk was found with IMPT (4%). The risks associated with conventional photon therapy, electron therapy and IMET were 20%, 21% and 15%, respectively. This model study shows that spinal irradiation of young children with photon and electron techniques results in a substantial risk of radiation-induced secondary cancers. Multiple beam IMXT seems to be associated with a particularly high risk of secondary cancer induction. To minimise this risk, IMPT should be the treatment of choice. If proton therapy is not available, advanced electron therapy may provide a better alternative.

  • 40. Rossi Norrlund, Rauni
    et al.
    Holback, Daniel
    Johansson, Lennart
    Umeå University, Faculty of Medicine, Department of Radiation Sciences, Radiation Physics.
    Hietala, Sven-Ola
    Umeå University, Faculty of Medicine, Department of Radiation Sciences, Diagnostic Radiology.
    Riklund, Katrine
    Umeå University, Faculty of Medicine, Department of Radiation Sciences, Diagnostic Radiology.
    Combinations of nonlabeled, 125I-labeled, and anti-idiotypic antiplacental alkaline phosphatase monoclonal antibodies at experimental radioimmunotargeting.1997In: Acta Radiologica, ISSN 0284-1851, E-ISSN 1600-0455, Vol. 38, no 6, p. 1087-1093Article in journal (Refereed)
    Abstract [en]

    Neither a preinjection of nonlabeled H7 nor a postinjection of alpha H7 nor a combination of both strategies resulted in improved tumor/nontumor dose ratios compared to a single injection of labeled H7. The monoclonal antibody H7 has a rapid and high uptake, combined with a prolonged retention time in the tumors. The kinetic properties of H7 are different from antibodies targeting intracellular tumor antigens.

  • 41. Rossi Norrlund, Rauni
    et al.
    Ullén, Anders
    Sandström, Per
    Holback, Daniel
    Johansson, Lennart
    Umeå University, Faculty of Medicine, Department of Radiation Sciences, Radiation Physics.
    Stigbrand, Torgny
    Umeå University, Faculty of Medicine, Department of Clinical Microbiology, Immunology/Immunchemistry.
    Hietala, Sven-Ola
    Umeå University, Faculty of Medicine, Department of Radiation Sciences, Diagnostic Radiology.
    Riklund, Katrine
    Umeå University, Faculty of Medicine, Department of Radiation Sciences, Diagnostic Radiology.
    Dosimetry of fractionated experimental radioimmunotargeting with idiotypic and anti-idiotypic anticytokeratin antibodies.1997In: Cancer, ISSN 0008-543X, E-ISSN 1097-0142, Vol. 80, no 12 Suppl, p. 2681-2688Article in journal (Refereed)
    Abstract [en]

    The fractionated strategy can contribute to a significant accumulation of radiolabeled TS1 in the tumors. Furthermore, the use of alphaTS1 makes it possible to increase the tumor-to-nontumor dose ratio and maintain a prolonged high activity accumulation in the tumor.

  • 42. Rossi Norrlund, Rauni
    et al.
    Ullén, Anders
    Sandström, Per
    Holback, Daniel
    Johansson, Lennart
    Umeå University, Faculty of Medicine, Department of Radiation Sciences, Radiation Physics.
    Stigbrand, Torgny
    Umeå University, Faculty of Medicine, Department of Clinical Microbiology, Immunology/Immunchemistry.
    Hietala, Sven-Ola
    Umeå University, Faculty of Medicine, Department of Radiation Sciences, Diagnostic Radiology.
    Riklund, Katrine
    Umeå University, Faculty of Medicine, Department of Radiation Sciences, Diagnostic Radiology.
    Experimental radioimmunotargeting combining nonlabeled, iodine-125-labeled, and anti-idiotypic anticytokeratin monoclonal antibodies: a dosimetric evaluation.1997In: Cancer, ISSN 0008-543X, E-ISSN 1097-0142, Vol. 80, no 12 Suppl, p. 2689-2698Article in journal (Refereed)
    Abstract [en]

    This study confirms an extensive accumulation of TS1 in the tumor, with peak values as late as 30 days after injection of labeled TS1. Furthermore, both preinjection of nonlabeled TS1 and postinjection of alphaTS1 can improve radioimmunotargeting.

  • 43.
    Rydh, Anders
    et al.
    Umeå University, Faculty of Medicine, Department of Radiation Sciences, Diagnostic Radiology.
    Riklund, Katrine
    Umeå University, Faculty of Medicine, Department of Radiation Sciences, Diagnostic Radiology.
    Widmark, Anders
    Umeå University, Faculty of Medicine, Department of Radiation Sciences, Oncology.
    Bergh, Anders
    Umeå University, Faculty of Medicine, Department of Medical Biosciences, Pathology.
    Johansson, Lennart
    Umeå University, Faculty of Medicine, Department of Radiation Sciences, Radiation Physics.
    Tavelin, Björn
    Umeå University, Faculty of Medicine, Department of Radiation Sciences, Oncology.
    Nilsson, Sten
    Stigbrand, Torgny
    Umeå University, Faculty of Medicine, Department of Clinical Microbiology, Immunology/Immunchemistry.
    Damber, Jan Erik
    Hietala, Sven-Ola
    Umeå University, Faculty of Medicine, Department of Radiation Sciences, Diagnostic Radiology.
    Radioimmunotherapy of DU-145 tumours in nude mice--a pilot study with E4, a novel monoclonal antibody against prostate cancer.1999In: Acta Oncologica, ISSN 0284-186X, E-ISSN 1651-226X, Vol. 38, no 8, p. 1075-1079Article in journal (Refereed)
    Abstract [en]

    The anti-tumour effect of the 131I-labelled antiprostate monoclonal antibody (MAb) E4 was studied in an experimental model with 41 nude mice, subcutaneously xenografted with a human prostate cancer cell line (DU-145). The mice were divided into four study groups, i.e. one receiving single and another repeated injections of the radiolabelled MAb. A third group was injected with non-labelled MAb, and the fourth served as an untreated control group. The tumour volumes increased similarly in all groups during the 27-day observation period. The tumour tissue was morphologically disintegrated in the group that received repeated radioimmunotherapy (RIT). The tumours from this group contained large fluid-filled cystic parts and demonstrated pronounced cellular and subcellular polymorphism in the remaining viable tumour tissue. The untreated control tumours and single therapy tumours remained solid. The proportion of the total tumour volume that consisted of viable tumour cells, as determined by morphometric techniques, was significantly lower in the 131I-E4-treated groups. The use of 131I-labelled E4 MAb has thus demonstrated a promising therapeutic potential.

  • 44.
    Rydh, Anders
    et al.
    Umeå University, Faculty of Medicine, Department of Radiation Sciences, Diagnostic Radiology.
    Riklund, Katrine
    Umeå University, Faculty of Medicine, Department of Radiation Sciences, Diagnostic Radiology.
    Widmark, Anders
    Umeå University, Faculty of Medicine, Department of Radiation Sciences, Oncology.
    Johansson, Lennart
    Umeå University, Faculty of Medicine, Department of Radiation Sciences, Radiation Physics.
    Nilsson, Sten
    Bergh, Anders
    Umeå University, Faculty of Medicine, Department of Medical Biosciences, Pathology.
    Damber, Jan Erik
    Stigbrand, T
    Hietala, Sven-Ola
    Umeå University, Faculty of Medicine, Department of Radiation Sciences, Diagnostic Radiology.
    Radioimmunoscintigraphy with a novel monoclonal antiprostate antibody (E4): an experimental study in nude mice.1997In: Cancer, ISSN 0008-543X, E-ISSN 1097-0142, Vol. 80, no 12 Suppl, p. 2398-2403Article in journal (Refereed)
    Abstract [en]

    The MoAb E4 is a promising radiotracer for prostate cancer and may be used in radioimmunotherapy. As in earlier studies, TS1 shows significant radioimmunolocalization into necrotic tumor tissue, which also exists in prostate cancer.

  • 45.
    Rydh, Anders
    et al.
    Umeå University, Faculty of Medicine, Radiation Sciences, Diagnostic Radiology.
    Riklund Åhlström, Katrine
    Umeå University, Faculty of Medicine, Radiation Sciences, Diagnostic Radiology.
    Widmark, Anders
    Umeå University, Faculty of Medicine, Radiation Sciences, Oncology.
    Johansson, Lennart
    Umeå University, Faculty of Medicine, Radiation Sciences, Radiation Physics.
    Nilsson, S
    Bergh, A
    Umeå University, Faculty of Medicine, Medical Biosciences, Pathology.
    Damber, J E
    Stigbrand, T
    Hietala, S O
    Umeå University, Faculty of Medicine, Radiation Sciences, Diagnostic Radiology.
    Radioimmunoscintigraphy using an anti-prostate monoclonal antibody (E4): a dosimetric evaluation.2001In: Urological research, ISSN 0300-5623, E-ISSN 1434-0879, Vol. 29, no 3, p. 216-20Article in journal (Refereed)
    Abstract [en]

    The aim of this study was to evaluate different strategies to increase the tumour radiation dose for experimental radioimmunotherapy using 125I-labelled monoclonal antibody (MAb) E4 in a nude mice model xenografted with DU-145 tumours. The effects from a single injection of the 125I-labelled MAb E4, the same total amount of radiolabelled MAb E4 divided into three repeated injections, and the effect of pre-targeting with non-labelled MAb E4 for reducing the amount of shed antigen were investigated. Based on repetitive quantitative radioimmunoscintigraphies, calculation of the tumour radiation dose delivered from the 125I-nuclide was performed for each strategy. The single injection strategy without pretargeting rendered the highest mean tumour radiation dose, i.e. 0.23 Gy/MBq. Pretargeting with non-labelled MAb E4 before a single injection of [125I]E4 resulted in a slightly lower mean tumour radiation dose, i.e. 0.19 Gy/MBq, compared to the single injection alone. An even lower mean tumour radiation dose, i.e. 0.14 Gy/MBq, was obtained when the same total administered amount of activity was divided into three separate injections given in 10-day intervals. We concluded that the single injection strategy is the most efficient when using MAb E4 in this tumour model. The tumour radiation doses were not increased by dividing the same amount of activity into three injections or by pretargeting with non-labelled MAb E4.

  • 46.
    Rydh, Anders
    et al.
    Umeå University, Faculty of Medicine, Radiation Sciences, Diagnostic Radiology.
    Åhlström Riklund, Katrine
    Umeå University, Faculty of Medicine, Radiation Sciences, Diagnostic Radiology.
    Larsson, Anne
    Umeå University, Faculty of Medicine, Radiation Sciences, Radiation Physics.
    Johansson, Lennart
    Umeå University, Faculty of Medicine, Radiation Sciences, Radiation Physics.
    Damber, J E
    Tomiç, R
    Hietala, S O
    Umeå University, Faculty of Medicine, Radiation Sciences, Diagnostic Radiology.
    Quantitative bone scintigraphy. A methodological evaluation in prostate cancer.2000In: Acta Radiologica, ISSN 0284-1851, E-ISSN 1600-0455, Vol. 41, no 2, p. 183-8Article in journal (Refereed)
    Abstract [en]

    PURPOSE: To evaluate a simple method for quantification of focal activity in bone scintigraphy (BS). MATERIAL AND METHODS: The gamma camera was calibrated using a phantom. Quantitative bone scintigraphy (QBS) was performed on 11 men recently diagnosed with prostate cancer (PCa), for whom routine BS showed involvement of the skeleton. Following endocrine therapy for 4 to 8 months, a second QBS was performed. Changes in QBS values were then compared to changes in serum levels of prostate-specific antigen (PSA). RESULTS: PSA response indicating regression of PCa was accompanied by a decrease in the QBS value in 8 of the 11 patients. The overall mean error of the QBS values was 15%. CONCLUSION: QBS according to this method is a relatively simple procedure that might contribute to objective evaluation of therapeutic effects in skeletal metastases, although its validity must be tested in a larger clinical material.

  • 47.
    Sandgren, Kristina
    et al.
    Umeå University, Faculty of Medicine, Department of Radiation Sciences, Radiation Physics.
    Johansson, Lennart
    Umeå University, Faculty of Medicine, Department of Radiation Sciences, Radiation Physics.
    Axelsson, Jan
    Umeå University, Faculty of Medicine, Department of Radiation Sciences, Radiation Physics.
    Jonsson, Joakim
    Umeå University, Faculty of Medicine, Department of Radiation Sciences, Radiation Physics.
    Ögren, Mattias
    Umeå University, Faculty of Medicine, Department of Radiation Sciences, Diagnostic Radiology.
    Ögren, Margareta
    Umeå University, Faculty of Medicine, Department of Radiation Sciences, Diagnostic Radiology.
    Andersson, Martin
    Strandberg, Sara
    Umeå University, Faculty of Medicine, Department of Radiation Sciences.
    Nyholm, Tufve
    Umeå University, Faculty of Medicine, Department of Radiation Sciences, Radiation Physics.
    Riklund, Katrine
    Umeå University, Faculty of Medicine, Department of Radiation Sciences, Diagnostic Radiology.
    Widmark, Anders
    Umeå University, Faculty of Medicine, Department of Radiation Sciences, Radiation Physics.
    Radiation dosimetry of [Ga-68]PSMA-11 in low-risk prostate cancer patients2019In: EJNMMI Physics, ISSN 2197-7364, E-ISSN 2191-219X, Vol. 6, article id 2Article in journal (Refereed)
    Abstract [en]

    Background: 68Ga-labeled Glu-NH-CO-NH-Lys(Ahx)-HBED-CC ([68Ga]PSMA-11) has been increasingly used to image prostate cancer using positron emission tomography (PET)/computed tomography (CT) both during diagnosis and treatment planning. It has been shown to be of clinical value for patients both in the primary and secondary stages of prostate cancer. The aim of this study was to determine the effective dose and organ doses from injection of [68Ga]PSMA-11 in a cohort of low-risk prostate cancer patients.

    Methods: Six low-risk prostate cancer patients were injected with 133–178 MBq [68Ga]PSMA-11 and examined with four PET/CT acquisitions from injection to 255 min post-injection. Urine was collected up to 4 h post-injection, and venous blood samples were drawn at 45 min, 85 min, 175 min, and 245 min post-injection. Kidneys, liver, lungs, spleen, salivary and lacrimal glands, and total body where delineated, and cumulated activities and absorbed organ doses calculated. The software IDAC-Dose 2.1 was used to calculate absorbed organ doses according to the International Commission on Radiological Protection (ICRP) publication 107 using specific absorbed fractions published in ICRP 133 and effective dose according to ICRP Publication 103. We also estimated the absorbed dose to the eye lenses using Monte Carlo methods.

    Results: [68Ga]PSMA-11 was rapidly cleared from the blood and accumulated preferentially in the kidneys and the liver. The substance has a biological half-life in blood of 6.5 min (91%) and 4.4 h (9%). The effective dose was calculated to 0.022 mSv/MBq. The kidneys received approximately 40 mGy after an injection with 160 MBq [68Ga]PSMA-11 while the lacrimal glands obtained an absorbed dose of 0.12 mGy per administered MBq. Regarding the eye lenses, the absorbed dose was low (0.0051 mGy/MBq).

    Conclusion: The effective dose for [68Ga]PSMA-11 is 0.022 mSv/MBq, where the kidneys and lacrimal glands receiving the highest organ dose.

  • 48.
    Sheikholvaezin, Ali
    et al.
    Umeå University, Faculty of Medicine, Clinical Microbiology, Immunology/Immunchemistry.
    Eriksson, David
    Umeå University, Faculty of Medicine, Clinical Microbiology, Immunology/Immunchemistry.
    Riklund Ahlström, Katrine
    Umeå University, Faculty of Medicine, Radiation Sciences, Diagnostic Radiology.
    Johansson, Lennart
    Umeå University, Faculty of Medicine, Radiation Sciences, Radiation Physics.
    Stigbrand, Torgny
    Umeå University, Faculty of Medicine, Clinical Microbiology, Immunology/Immunchemistry.
    Tumor radioimmunolocalization in nude mice by mono- and divalent- single-chain Fv antiplacental alkaline phosphatase antibodies.2007In: Cancer Biotherapy and Radiopharmaceuticals, ISSN 1084-9785, E-ISSN 1557-8852, Vol. 22, no 1, p. 64-72Article in journal (Refereed)
    Abstract [en]

    One single-chain Fv antibody fragment (scFv) and a new recombinant covalently linked dimeric scFv antibody (sc(Fv)(2)) against placental alkaline phosphatase (PLAP) were investigated for selective tumor targeting. The biological behavior of these new antibodies was compared to that of the original native antibody, H7 MAb. The sc(Fv)(2)) antibody displayed convincing tumor localization properties with a rapid excretion pattern comparable to the scFv, but with a longer retention time in the tumor, and higher tumor-to-nontumor ratio (27:1), compared to the scFv (15:1), at 48 hours. For the sc(Fv)(2) antibody, more than 50% of the remaining activity in the mouse was present in the tumor between 24 and 48 hours after the injection. With this antibody, scintigraphic visualization of the tumor was also possible 1 week after the injection. It is concluded that this sc(Fv)(2) antibody fragment, with two binding sites, displays properties suitable for in vivo targeting of PLAP expressing tumors.

  • 49. Ullén, Anders
    et al.
    Sandström, Per
    Rossi Norrlund, Rauni
    Rathsman, Sandra
    Johansson, Lennart
    Umeå University, Faculty of Medicine, Department of Radiation Sciences, Radiation Physics.
    Riklund, Katrine
    Umeå University, Faculty of Medicine, Department of Radiation Sciences, Diagnostic Radiology.
    Hietala, Sven-Ola
    Umeå University, Faculty of Medicine, Department of Radiation Sciences, Diagnostic Radiology.
    Stigbrand, Torgny
    Umeå University, Faculty of Medicine, Department of Clinical Microbiology, Immunology/Immunchemistry.
    Dosimetry of fractionated administration of 125I-labeled antibody at experimental radioimmunotargeting.1997In: Cancer, ISSN 0008-543X, E-ISSN 1097-0142, Vol. 80, no 12 Suppl, p. 2510-2518Article in journal (Refereed)
    Abstract [en]

    In this antigen target system, a single injection of a large amount of antibody was found to be more efficient than the same antibody dose subdivided into three or ten fractions. It was concluded that not only the radioactivity but also the amount of antibody per fraction should be considered when determining optimal fractionated radioimmunotherapy.

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