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Carbon Flux as a Measure of Prostate CancerAggressiveness: [11C]-Acetate PET/CT
Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Surgical Sciences. Uppsala University.
Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Surgical Sciences.
Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Surgical Sciences, Radiology.
Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Surgical Sciences.
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2020 (English)In: International Journal of Medical Sciences, ISSN 1449-1907, E-ISSN 1449-1907, international journal of medical sciences, ISSN 1449-1907, Vol. 17, no 2, p. 214-223Article in journal (Refereed) Published
Abstract [en]

Purpose: Dynamic [11C]-acetate positron emission tomography (PET) can be used to study tissue perfusion and carbon flux simultaneously. In this study, the feasibility of the quantification of prostate cancer aggressiveness using parametric methods assessing [11C]-acetate kinetics was investigated in prostate cancer subjects. The underlying uptake mechanism correlated with [11C]-acetate influx and efflux measured in real-time in vitro in cell culture.

Methods: Twenty-one patients with newly diagnosed low-to-moderate risk prostate cancer underwent magnetic resonance imaging (MRI) and dynamic [11C]-acetate PET/CT examinations of the pelvis. Parametric images of K1 (extraction × perfusion), k2 (oxidative metabolism) and VT (=K1/k2, anabolic metabolism defined as carbon retention) were constructed using a one-tissue compartment model with an arterial input function derived from pelvic arteries. Regions of interest (ROIs) of the largest cancer lesion in each patient and normal prostate tissue were drawn using information from MRI (T2 and DWI images), biopsy results, and post-surgical histopathology of whole prostate sections (n=7). In vitro kinetics of [11C]-acetate were studied on DU145 andPC3 cell lines using LigandTracer® White equipment for the measurement of the radioactivity uptake in real-time at 37°C.

Results: Mean prostate specific antigen (PSA) was 8.33±3.92 ng/mL and median Gleason Sum 6 (range 5-7). K1,VT and standardized uptake values (SUVs) were significantly higher in cancerous prostate tissues compared to normal ones for all patients (p<0.001), while k2 was not (p=0.26). PSA values correlated to early SUVs (r=0.50,p=0.02) and K1 (r=0.48, p=0.03). Early and late SUVs correlated to VT (r>0.76, p<0.001) and K1 (r>0.64,p<0.005). In vitro studies demonstrated higher extraction and retention (p<0.01) of [11C]-acetate in the more aggressive PC3 cells.

Conclusion: Parametric images could be used to visualize the [11C]-acetate kinetics of the prostate cancer exhibiting elevated extraction associated with the cancer aggressiveness. The influx rate of [11C]-acetate studied in cell culture also showed dependence on the cancer aggressiveness associated with elevated lipogenesis. Dynamic [11C]-acetate/PET demonstrated potential for prostate cancer aggressiveness estimation using parametric-based K1 and VT values.

Place, publisher, year, edition, pages
2020. Vol. 17, no 2, p. 214-223
Keywords [en]
carbon-11 acetate, positron emission tomography, prostate cancer, dynamic imaging
National Category
Cancer and Oncology
Research subject
Oncology
Identifiers
URN: urn:nbn:se:uu:diva-407036OAI: oai:DiVA.org:uu-407036DiVA, id: diva2:1415458
Funder
Swedish Cancer Society, CAN2016/835Available from: 2020-03-18 Created: 2020-03-18 Last updated: 2020-03-18
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