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Hietala, Sven-Ola
Publications (10 of 16) Show all publications
Rydh, A., Riklund, K., Widmark, A., Bergh, A., Johansson, L., Tavelin, B., . . . Hietala, S.-O. (1999). Radioimmunotherapy of DU-145 tumours in nude mice--a pilot study with E4, a novel monoclonal antibody against prostate cancer.. Acta Oncologica, 38(8), 1075-1079
Open this publication in new window or tab >>Radioimmunotherapy of DU-145 tumours in nude mice--a pilot study with E4, a novel monoclonal antibody against prostate cancer.
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1999 (English)In: Acta Oncologica, ISSN 0284-186X, E-ISSN 1651-226X, Vol. 38, no 8, p. 1075-1079Article in journal (Refereed) Published
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.

Identifiers
urn:nbn:se:umu:diva-41867 (URN)10665766 (PubMedID)
Available from: 2011-04-01 Created: 2011-04-01 Last updated: 2018-06-08
Johansson, A., Sandström, P., Ullén, A., Erlandsson, A., Sundström, B., Riklund, K., . . . Stigbrand, T. (1999). Stability and immunoreactivity of the monoclonal anticytokeratin antibody TS1 after different degrees of iodination.. Acta Oncologica, 38(3), 329-334
Open this publication in new window or tab >>Stability and immunoreactivity of the monoclonal anticytokeratin antibody TS1 after different degrees of iodination.
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1999 (English)In: Acta Oncologica, ISSN 0284-186X, E-ISSN 1651-226X, Vol. 38, no 3, p. 329-334Article in journal (Refereed) Published
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.

Identifiers
urn:nbn:se:umu:diva-41872 (URN)10380824 (PubMedID)
Available from: 2011-04-01 Created: 2011-04-01 Last updated: 2018-06-08
Rydh, A., Suhr, O. B., Hietala, S.-O., Riklund, K., Pepys, M. B. & Hawkins, P. N. (1998). Serum amyloid P component scintigraphy in familial amyloid polyneuropathy: regression of visceral amyloid following liver transplantation.. European Journal of Nuclear Medicine, 25(7), 709-713
Open this publication in new window or tab >>Serum amyloid P component scintigraphy in familial amyloid polyneuropathy: regression of visceral amyloid following liver transplantation.
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1998 (English)In: European Journal of Nuclear Medicine, ISSN 0340-6997, E-ISSN 1432-105X, Vol. 25, no 7, p. 709-713Article in journal (Refereed) Published
Abstract [en]

Familial amyloid polyneuropathy (FAP) associated with transthyretin (TTR) mutations is the commonest type of hereditary amyloidosis. Plasma TTR is produced almost exclusively in the liver and orthotopic liver transplantation is the only available treatment, although the clinical outcome varies. Serum amyloid P component (SAP) scintigraphy is a method for identifying and quantitatively monitoring amyloid deposits in vivo, but it has not previously been used to study the outcome of visceral amyloid deposits in FAP following liver transplantation. Whole body scintigraphy following injection of iodine-123 labelled SAP was performed in 17 patients with FAP associated with TTR Met30 and in five asymptomatic gene carriers. Follow-up studies were performed in ten patients, eight of whom had undergone orthotopic liver transplantation 1-5 years beforehand. There was abnormal uptake of 123I-SAP in all FAP patients, including the kidneys in each case, the spleen in five cases and the adrenal glands in three cases. Renal amyloid deposits were also present in three of the asymptomatic carriers. Follow-up studies 1-5 years after liver transplantation showed that there had been substantial regression of the visceral amyloid deposits in two patients and modest improvement in three cases. The amyloid deposits were unchanged in two patients. In conclusion, 123I-SAP scintigraphy identified unsuspected visceral amyloid in each patient with FAP due to TTR Met30. The universal presence of renal amyloid probably underlies the high frequency of renal failure that occurs in FAP following liver transplantation. The variable capacity of patients to mobilise amyloid deposits following liver transplantation may contribute to their long-term clinical outcome.

Identifiers
urn:nbn:se:umu:diva-41874 (URN)9662592 (PubMedID)
Available from: 2011-04-01 Created: 2011-04-01 Last updated: 2018-06-08
Rossi Norrlund, R., Holback, D., Johansson, L., Hietala, S.-O. & Riklund, K. (1997). Combinations of nonlabeled, 125I-labeled, and anti-idiotypic antiplacental alkaline phosphatase monoclonal antibodies at experimental radioimmunotargeting.. Acta Radiologica, 38(6), 1087-1093
Open this publication in new window or tab >>Combinations of nonlabeled, 125I-labeled, and anti-idiotypic antiplacental alkaline phosphatase monoclonal antibodies at experimental radioimmunotargeting.
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1997 (English)In: Acta Radiologica, ISSN 0284-1851, E-ISSN 1600-0455, Vol. 38, no 6, p. 1087-1093Article in journal (Refereed) Published
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.

Identifiers
urn:nbn:se:umu:diva-41887 (URN)9394676 (PubMedID)
Available from: 2011-04-01 Created: 2011-04-01 Last updated: 2018-06-08
Ullén, A., Sandström, P., Rossi Norrlund, R., Rathsman, S., Johansson, L., Riklund, K., . . . Stigbrand, T. (1997). Dosimetry of fractionated administration of 125I-labeled antibody at experimental radioimmunotargeting.. Cancer, 80(12 Suppl), 2510-2518
Open this publication in new window or tab >>Dosimetry of fractionated administration of 125I-labeled antibody at experimental radioimmunotargeting.
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1997 (English)In: Cancer, ISSN 0008-543X, E-ISSN 1097-0142, Vol. 80, no 12 Suppl, p. 2510-2518Article in journal (Refereed) Published
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.

Identifiers
urn:nbn:se:umu:diva-41879 (URN)9406704 (PubMedID)
Available from: 2011-04-01 Created: 2011-04-01 Last updated: 2018-06-08
Rossi Norrlund, R., Ullén, A., Sandström, P., Holback, D., Johansson, L., Stigbrand, T., . . . Riklund, K. (1997). Dosimetry of fractionated experimental radioimmunotargeting with idiotypic and anti-idiotypic anticytokeratin antibodies.. Cancer, 80(12 Suppl), 2681-2688
Open this publication in new window or tab >>Dosimetry of fractionated experimental radioimmunotargeting with idiotypic and anti-idiotypic anticytokeratin antibodies.
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1997 (English)In: Cancer, ISSN 0008-543X, E-ISSN 1097-0142, Vol. 80, no 12 Suppl, p. 2681-2688Article in journal (Refereed) Published
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.

Identifiers
urn:nbn:se:umu:diva-41894 (URN)9406725 (PubMedID)
Available from: 2011-04-01 Created: 2011-04-01 Last updated: 2018-06-08
Rossi Norrlund, R., Ullén, A., Sandström, P., Holback, D., Johansson, L., Stigbrand, T., . . . Riklund, K. (1997). Experimental radioimmunotargeting combining nonlabeled, iodine-125-labeled, and anti-idiotypic anticytokeratin monoclonal antibodies: a dosimetric evaluation.. Cancer, 80(12 Suppl), 2689-2698
Open this publication in new window or tab >>Experimental radioimmunotargeting combining nonlabeled, iodine-125-labeled, and anti-idiotypic anticytokeratin monoclonal antibodies: a dosimetric evaluation.
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1997 (English)In: Cancer, ISSN 0008-543X, E-ISSN 1097-0142, Vol. 80, no 12 Suppl, p. 2689-2698Article in journal (Refereed) Published
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.

Identifiers
urn:nbn:se:umu:diva-41889 (URN)9406726 (PubMedID)
Available from: 2011-04-01 Created: 2011-04-01 Last updated: 2018-06-08
Rydh, A., Riklund, K., Widmark, A., Johansson, L., Nilsson, S., Bergh, A., . . . Hietala, S.-O. (1997). Radioimmunoscintigraphy with a novel monoclonal antiprostate antibody (E4): an experimental study in nude mice.. Cancer, 80(12 Suppl), 2398-2403
Open this publication in new window or tab >>Radioimmunoscintigraphy with a novel monoclonal antiprostate antibody (E4): an experimental study in nude mice.
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1997 (English)In: Cancer, ISSN 0008-543X, E-ISSN 1097-0142, Vol. 80, no 12 Suppl, p. 2398-2403Article in journal (Refereed) Published
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.

Identifiers
urn:nbn:se:umu:diva-41886 (URN)9406689 (PubMedID)
Available from: 2011-04-01 Created: 2011-04-01 Last updated: 2018-06-08
Riklund, K., Makiya, R. E., Ullén, A. P., Damber, J. E., Hietala, S.-O. & Stigbrand, T. (1996). A putative mechanism for the non-specific uptake of intact radiolabelled monoclonal antibodies in the testes and prostate.. Acta Oncologica, 35(3), 303-307
Open this publication in new window or tab >>A putative mechanism for the non-specific uptake of intact radiolabelled monoclonal antibodies in the testes and prostate.
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1996 (English)In: Acta Oncologica, ISSN 0284-186X, E-ISSN 1651-226X, Vol. 35, no 3, p. 303-307Article in journal (Refereed) Published
Abstract [en]

Non-specific testicular accumulation of radiolabelled intact anti-CEA monoclonal antibody (MAb), (A431/26, Behringwerke AG) was observed in 11 out of 12 patients with the testes and prostate included in the examination field at radioimmunoscintigraphy (RIS). Previous studies have shown that placental alkaline phosphatase (PLAP) serves as an Fc-receptor, mediating IgG transport through the placenta. A closely related protein, the germ cell alkaline phosphatase (GCAP), is expressed in the testes. The testicular uptake of IgG is observed only when intact but not fragmented MAbs are used, indicating involvement of Fc-receptors. MDCK cells (dog kidney cell line) transfected with the plasmid pSVT7 containing the GCAP gene were shown to acquire the capacity to both express membrane bound GCAP and to bind IgG on the cell surface. This might indicate that GCAP is responsible for the non-specific accumulation of intact MAb in the testes and prostate often observed when intact murine MAbs are used for radioimmunolocalization (RIL).

Identifiers
urn:nbn:se:umu:diva-41917 (URN)8679260 (PubMedID)
Available from: 2011-04-04 Created: 2011-04-04 Last updated: 2018-06-08
Ullén, A., Riklund, K., Hietala, S.-O., Nilsson, B., Ärlestig, L. & Stigbrand, T. (1996). Secondary antibodies as tools to improve tumor to non tumor ratio at radioimmunolocalisation and radioimmunotherapy.. Acta Oncologica, 35(3), 281-285
Open this publication in new window or tab >>Secondary antibodies as tools to improve tumor to non tumor ratio at radioimmunolocalisation and radioimmunotherapy.
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1996 (English)In: Acta Oncologica, ISSN 0284-186X, E-ISSN 1651-226X, Vol. 35, no 3, p. 281-285Article in journal (Refereed) Published
Abstract [en]

One way of selectively improving the efficiency of radioimmunolocalization and radioimmunotherapy is to eliminate redundant, circulating, non-targeting radiolabeled antibodies after saturation of the target sites. Secondary antibodies of different types have been proposed as clearing agents for such purposes. The conceptually different approaches of the 'secondary antibody' strategy including its advantages and limitations are discussed. This mini-review also presents a model describing the kinetics of the components (the antigen, the primary and secondary antibodies) and approaches required to improve the efficacy of both radioimmunolocalization and radioimmunotherapy.

Identifiers
urn:nbn:se:umu:diva-41916 (URN)8679257 (PubMedID)
Available from: 2011-04-04 Created: 2011-04-04 Last updated: 2018-06-08
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