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

Abstract

Purpose: Dynamic [ 11 C]-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 [ 11 C]-acetate kinetics was investigated in prostate cancer subjects. The underlying uptake mechanism correlated with [ 11 C]-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 [ 11 C]-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 [ 11 C]-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 [ 11 C]-acetate in the more aggressive PC3 cells. Conclusion: Parametric images could be used to visualize the [ 11 C]-acetate kinetics of the prostate cancer exhibiting elevated extraction associated with the cancer aggressiveness. The influx rate of [ 11 C]-acetate studied in cell culture also showed dependence on the cancer aggressiveness associated with elevated lipogenesis. Dynamic [ 11 C]-acetate/PET demonstrated potential for prostate cancer aggressiveness estimation using parametric-based K1 and VT values.

Tumour blood flow for prediction of human prostate cancer aggressiveness: a study with Rubidium-82 PET, MRI and Na+/K+-ATPase-density

“…In our previous studies on PCa, we found a positive correlation between cancer aggressiveness and TBF, measured with both [ 15 O]H 2 O and 82 Rb PET [10,23]. Similar results were found when studying K 1 influx of other tracers including [ 18 F]flourocholine [24,25], [ 11 C]donepezil [26], and [ 11 C]acetate [27]. Consequently, quantitative TBF measurement may be promising in PCa imaging.…”

Potential synergy between PSMA uptake and tumour blood flow for prediction of human prostate cancer aggressiveness

“…An advantage is that PSMA PET and TBF are very much within clinical reach, as PSMA PET is already a dominating imaging modality in PCa imaging, and TBF can be estimated with various modalities. Other studies found correlations between PCa aggressiveness and K 1 influx of other tracers including [ 15 O]-H 2 O [ 17 ], [ 18 F]-flourocholine [ 48 , 49 ], [ 11 C]-donepezil [ 50 ], and [ 11 C]-acetate [ 51 ]. The authors believe that the most promising applications of this combined analysis is characterization of tumour metabolism for primary risk evaluation and monitoring more than for detection of biochemical recurrence.…”