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Radiolabeled acetate PET in oncology imaging: studies on head and neck cancer, prostate cancer and normal distribution
Umeå University, Faculty of Medicine, Radiation Sciences, Oncology.
2010 (English)Doctoral thesis, comprehensive summary (Other academic)
Abstract [en]

The use of positron emission tomography (PET) for imaging in oncology has grown rapidly in recent years. 2-[18F]-fluorodeoxyglucose (FDG) is the most common tracer of PET, although drawbacks exist. Radiolabeled 1-[11C]-acetate (C-AC) is a simple probe for evaluation of perfusion, anabolism (lipogenesis) and catabolism (oxidative metabolism) in all living tissues. This study explored the potential of AC PET in head and neck cancer, benign and malignant lymph nodes in prostate cancer and normal distribution. 

In head and neck cancer, C-AC PET detected more primaries and lymph node metastases than FDG PET. The mean primary tumor volumes delineated by C-AC was 51% larger than that of FDG before radiotherapy (RT). Both FDG and C-AC PET tumor volumes must be carefully validated before used in clinical routine. Baseline tumor clearance rate (kmono) was higher in complete responders (CR) than that in partial responders (PR). kmono tended to correlate inversely with FDG SUV at baseline. Radiosensitive tumors might rely predominantly on oxidative metabolism for their biogenetic needs. kmono increased in PR during RT. The potential reversibility of impaired kmono in radioresistant tumors imply that treatment targeting the intermediary metabolism might improve the outcome. Tumor relative perfusion index (rF) and kmono were coupled in CR throughout the RT, but not in PR. Dynamic C-AC PET provides a new non-invasive method to simultaneously evaluate the tumor oxidative metabolism and perfusion which link the RT response in patients by a single tracer injection.

In prostate cancer, elevated C-AC accumulation is common in benign inguinal lymph nodes, probably due to increased lipogenesis rather than lymphatic drainage. CT Hounsfield unit of benign nodes was lower than that of metastases, suggesting that density measurement using CT might improve the specificity of nodal staging of prostate cancer.

A novel tracer 2-[18F]-fluoroacetate (F-AC) was synthesized and used for dynamic PET-CT imaging in animals. Compared with C-AC PET-CT, F-AC showed prolonged blood retention, no detectable trapping in myocardium and salivary glands, rapid excretion from liver to bile and urine and de-fluorination resulting in intensive skeletal activity. F-AC does not mimic the normal physiologic path of C-AC and appears to be of little use for assessment of perfusion, intermediary metabolism or lipogenesis.

Place, publisher, year, edition, pages
Umeå: Umeå university , 2010. , 62 p.
Series
Umeå University medical dissertations, ISSN 0346-6612 ; 1338
Keyword [en]
11C-acetate, 18F-fluoroacetate, PET, head and neck cancer, staging, delineating tumor volume, clearance rate, perfusion, RT, treatment outcome, benign and malignant lymph node, prostate cancer, normal distribution
National Category
Cancer and Oncology
Research subject
Oncology
Identifiers
URN: urn:nbn:se:umu:diva-32980ISBN: 978-91-7264-967-5 (print)OAI: oai:DiVA.org:umu-32980DiVA: diva2:307615
Public defence
2010-04-28, Sal 244 Lionssalen, By 7, Norrlands universitetssjukhus, Umeå, 09:00 (English)
Opponent
Supervisors
Available from: 2010-04-06 Created: 2010-04-01 Last updated: 2010-04-06Bibliographically approved
List of papers
1. 1-[11C]-acetate PET imaging in head and neck cancer: a comparison with 18F-FDG-PET: implications for staging and radiotherapy planning
Open this publication in new window or tab >>1-[11C]-acetate PET imaging in head and neck cancer: a comparison with 18F-FDG-PET: implications for staging and radiotherapy planning
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2007 (English)In: European Journal of Nuclear Medicine and Molecular Imaging, ISSN 1619-7070, Vol. 34, no 5, 651-657 p.Article in journal (Refereed) Published
Keyword
11C-acetate, 18F-FDG, PET, head and neck cancer, SUV
National Category
Cancer and Oncology
Research subject
Oncology
Identifiers
urn:nbn:se:umu:diva-13024 (URN)10.1007/s00259-006-0298-9 (DOI)17146654 (PubMedID)
Available from: 2007-04-27 Created: 2007-04-27 Last updated: 2010-04-06Bibliographically approved
2. Imaging tumor perfusion and oxidative metabolism in patients with head and neck cancer using 1-[11C]-acetate PET during radiotherapy: preliminary results
Open this publication in new window or tab >>Imaging tumor perfusion and oxidative metabolism in patients with head and neck cancer using 1-[11C]-acetate PET during radiotherapy: preliminary results
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(English)Manuscript (preprint) (Other academic)
National Category
Cancer and Oncology
Research subject
Oncology
Identifiers
urn:nbn:se:umu:diva-32611 (URN)
Available from: 2010-03-18 Created: 2010-03-18 Last updated: 2010-04-06Bibliographically approved
3. Characterizing benign and malignant lymph nodes using 1-[11C]-acetate PET/CT in biochemical relapsing prostate cancer patients
Open this publication in new window or tab >>Characterizing benign and malignant lymph nodes using 1-[11C]-acetate PET/CT in biochemical relapsing prostate cancer patients
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(English)Manuscript (preprint) (Other academic)
National Category
Cancer and Oncology
Research subject
Oncology
Identifiers
urn:nbn:se:umu:diva-32612 (URN)
Available from: 2010-03-18 Created: 2010-03-18 Last updated: 2010-04-06Bibliographically approved
4. [18F]-fluoroacetate is not a functional analogue of [11C]-acetate in normal physiology
Open this publication in new window or tab >>[18F]-fluoroacetate is not a functional analogue of [11C]-acetate in normal physiology
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2009 (English)In: European Journal of Nuclear Medicine and Molecular Imaging, ISSN 1619-7070, Vol. 36, no 9, 1453-1459 p.Article in journal (Refereed) Published
Abstract [en]

PURPOSE: [11C]-Acetate (C-AC) is a general PET tracer of cellular carbon flux and useful for clinical imaging in heart disease as well as prostate cancer and other tumours. C-AC has a high (70%) whole-body extraction fraction, proportional to blood flow in many organs. Trapping is related to organ-specific enzymatic activation and formation of [11C]-acetyl-CoA, the fate of which has been well characterized. Due to the logistic challenges with C-AC, 2-[18F]-fluoroacetate (F-AC) has been proposed as a marker for prostate cancer imaging.

METHOD: We evaluated the potential of F-AC as a tracer for imaging blood flow and early enzymatic steps in the intermediary metabolism. C-AC and F-AC were injected serially in three cynomolgus monkeys and one domestic pig and scanned using PET/CT. A dynamic scan covering heart and liver was followed by repeated whole-body imaging. Kinetic patterns were compared for the myocardium, liver, blood and other organs.

RESULTS: C-AC kinetics and organ distribution in both species were similar to those previously established in man. In contrast, F-AC showed prolonged blood retention, no detectable trapping in myocardium or salivary glands, rapid clearance from liver and extensive excretion to bile and urine. Massive defluorination was seen in the pig, resulting in intense skeletal activity.

CONCLUSION: 2-[18F]-Fluoroacetate cannot be regarded as a functional analogue of 1-[11C]-acetate in normal physiology and appears to be of little use for studies of organ blood flow, intermediary metabolism or lipid synthesis.

National Category
Cancer and Oncology
Research subject
Oncology
Identifiers
urn:nbn:se:umu:diva-30856 (URN)10.1007/s00259-009-1128-7 (DOI)19387639 (PubMedID)
Available from: 2010-01-20 Created: 2010-01-20 Last updated: 2010-04-06Bibliographically approved

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Sun, Aijun

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