Assessment of Simplified Methods for Quantification of 18F-FDHT Uptake in Patients with Metastatic Castration-Resistant Prostate Cancer

F-18-fluorodihydrotestosterone (F-18-FDHT) PET/CT potentially provides a noninvasive method for assessment of androgen receptor expression in patients with metastatic castration-resistant prostate cancer (mCRPC). The objective of this study was to assess simplified methods for quantifying F-18-FDHT uptake in mCRPC patients and to assess effects of tumor perfusion on these F-18-FDHT uptake metrics. Methods: Seventeen mCRPC patients were included in this prospective observational multicenter study. Test and retest 30-min dynamic F-18-FDHT PET/CT scans with venous blood sampling were performed in 14 patients. In addition, arterial blood sampling and dynamic O-15-H2O scans were obtained in a subset of 6 patients. Several simplified methods were assessed: Patlak plots; SUV normalized to body weight (SUVBW), lean body mass (SUVLBM), whole blood (SUVWB), parent plasma activity concentration (SUVPP), area under the parent plasma curve (SUVAUC,PP), and area under the whole-blood input curve (SUVAUC,WB); and SUVBW corrected for sex hormone-binding globulin levels (SUVSHBG). Results were correlated with parameters derived from full pharmacokinetic F-18-FDHT and O-15-H2O. Finally, the repeatability of individual quantitative uptake metrics was assessed. Results: Eighty-seven F-18-FDHT-avid lesions were evaluated. F-18-FDHT uptake was best described by an irreversible 2-tissue-compartment model. Replacing the continuous metabolite-corrected arterial plasma input function with an image-derived input function in combination with venous sample data provided similar K-i results (R-2 = 0.98). Patlak K-i and SUVAUC,PP showed an excellent correlation (R-2 > 0.9). SUVBW showed a moderate correlation to K-i (R-2 = 0.70, presumably due to fast F-18-FDHT metabolism. When calculating SUVSHBG, correlation to K-i improved (R-2 = 0.88). The repeatability of full kinetic modeling parameters was inferior to that of simplified methods (repeatability coefficients. 36% vs., 28%, respectively). F-18-FDHT uptake showed minimal blood flow dependency. Conclusion: F-18-FDHT kinetics in mCRPC patients are best described by an irreversible 2-tissue-compartment model with blood volume parameter. SUVAUC, PP showed a near-perfect correlation with the irreversible 2-tissue-compartment model analysis and can be used for accurate quantification of F-18-FDHT uptake in whole-body PET/CT scans. In addition, SUVSHBG could potentially be used as an even simpler method to quantify F-18-FDHT uptake when less complex scanning protocols and accuracy are required.