Int J Med Sci 2020; 17(2):214-223. doi:10.7150/ijms.39542

Research Paper

Carbon Flux as a Measure of Prostate Cancer Aggressiveness: [11C]-Acetate PET/CT

Naresh Regula1*✉, Hadis Honarvar1*, Mark Lubberink1,4, Håkan Jorulf1, Sam Ladjevardi2, Michael Häggman2, Gunnar Antoni3, Jos Buijs5, Irina Velikyan1, Jens Sörensen1,6

1. Division of Nuclear Medicine and PET, Department of Surgical Sciences, Uppsala University, Uppsala, Sweden
2. Division of Urology, Department of Surgical Sciences, Uppsala University, Uppsala, Sweden
3. Division of Molecular Imaging, Department of Surgical Sciences, Uppsala University, Uppsala, Sweden
4. Medical Physics, Uppsala University Hospital, Uppsala, Sweden
5. Department of Immunology, Genetics and Pathology, Uppsala University, Uppsala, Sweden
6. PET Centre, Uppsala University Hospital, Uppsala, Sweden
*These authors contributed equally to this work

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Citation:
Regula N, Honarvar H, Lubberink M, Jorulf H, Ladjevardi S, Häggman M, Antoni G, Buijs J, Velikyan I, Sörensen J. Carbon Flux as a Measure of Prostate Cancer Aggressiveness: [11C]-Acetate PET/CT. Int J Med Sci 2020; 17(2):214-223. doi:10.7150/ijms.39542. Available from http://www.medsci.org/v17p0214.htm

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Abstract

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 and PC3 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.

Keywords: carbon-11 acetate, positron emission tomography, prostate cancer, dynamic imaging