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

¹⁸ F-fluorodihydrotestosterone ( ¹⁸ F-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 ¹⁸ F-FDHT uptake in mCRPC patients and to assess effects of tumor perfusion on these ¹⁸ F-FDHT uptake metrics. Methods: Seventeen mCRPC patients were included in this prospective observational multicenter study. Test and retest 30-min dynamic ¹⁸ F-FDHT PET/CT scans with venous blood sampling were performed in 14 patients. In addition, arterial blood sampling and dynamic ¹⁵ O-H ₂ O 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 ¹⁸ F-FDHT and ¹⁵ O-H ₂ O. Finally, the repeatability of individual quantitative uptake metrics was assessed. Results: Eighty-seven ¹⁸ F-FDHT-avid lesions were evaluated. ¹⁸ F-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 SUV _AUC,PP showed an excellent correlation ( R ² > 0.9). SUV _BW showed a moderate correlation to K _i ( R ² = 0.70, presumably due to fast ¹⁸ F-FDHT metabolism. When calculating SUV _SHBG , 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). ¹⁸ F-FDHT uptake showed minimal blood flow dependency. Conclusion: ¹⁸ F-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 ¹⁸ F-FDHT uptake in whole-body PET/CT scans. In addition, SUV _SHBG could potentially be used as an even simpler method to quantify ¹⁸ F-FDHT uptake when less complex scanning protocols and accuracy are required.
(© 2019 by the Society of Nuclear Medicine and Molecular Imaging.)