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

¹⁸F-fluorodihydrotestosterone (¹⁸F-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 ¹⁸F-FDHT uptake in mCRPC patients and to assess effects of tumor perfusion on these ¹⁸F-FDHT uptake metrics. Methods: Seventeen mCRPC patients were included in this prospective observational multicenter study. Test and retest 30-min dynamic ¹⁸F-FDHT PET/CT scans with venous blood sampling were performed in 14 patients. In addition, arterial blood sampling and dynamic ¹⁵O-H₂O scans were obtained in a subset of 6 patients. Several simplified methods were assessed: Patlak plots; SUV normalized to body weight (SUV_BW), lean body mass (SUV_LBM), whole blood (SUV_WB), parent plasma activity concentration (SUV_PP), area under the parent plasma curve (SUV_AUC,PP), and area under the whole-blood input curve (SUV_AUC,WB); and SUV_BW corrected for sex hormone-binding globulin levels (SUV_SHBG). Results were correlated with parameters derived from full pharmacokinetic ¹⁸F-FDHT and ¹⁵O-H₂O. Finally, the repeatability of individual quantitative uptake metrics was assessed. Results: Eighty-seven ¹⁸F-FDHT-avid lesions were evaluated. ¹⁸F-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 (R² = 0.98). Patlak K_i and SUV_AUC,PP showed an excellent correlation (R² > 0.9). SUV_BW showed a moderate correlation to K_i (R² = 0.70, presumably due to fast ¹⁸F-FDHT metabolism. When calculating SUV_SHBG, correlation to K_i improved (R² = 0.88). The repeatability of full kinetic modeling parameters was inferior to that of simplified methods (repeatability coefficients > 36% vs. < 28%, respectively). ¹⁸F-FDHT uptake showed minimal blood flow dependency. Conclusion:¹⁸F-FDHT kinetics in mCRPC patients are best described by an irreversible 2-tissue-compartment model with blood volume parameter. SUV_AUC,PP showed a near-perfect correlation with the irreversible 2-tissue-compartment model analysis and can be used for accurate quantification of ¹⁸F-FDHT uptake in whole-body PET/CT scans. In addition, SUV_SHBG could potentially be used as an even simpler method to quantify ¹⁸F-FDHT uptake when less complex scanning protocols and accuracy are required.