Gerbrand M Kramer1, Maqsood Yaqub2, Herbert A Vargas3, Robert C Schuit2, Albert D Windhorst2, Alfonsus J M van den Eertwegh4, Astrid A M van der Veldt5,6, Andries M Bergman5, Eva M Burnazi3, Jason S Lewis3,7, Sua Chua8, Kevin D Staton3, Brad J Beattie9, John L Humm9, Ian D Davis10, Andrew J Weickhardt11, Andrew M Scott11,12, Michael J Morris13,14, Otto S Hoekstra2, Adriaan A Lammertsma2. 1. Department of Radiology and Nuclear Medicine, Amsterdam UMC, Vrije Universiteit Amsterdam, Amsterdam, The Netherlands ge.kramer@vumc.nl. 2. Department of Radiology and Nuclear Medicine, Amsterdam UMC, Vrije Universiteit Amsterdam, Amsterdam, The Netherlands. 3. Department of Radiology, Memorial Sloan Kettering Cancer Center, New York, New York. 4. Department of Medical Oncology, Amsterdam UMC, Vrije Universiteit Amsterdam, Amsterdam, The Netherlands. 5. Department of Medical Oncology, Netherlands Cancer Institute, Amsterdam, The Netherlands. 6. Departments of Medical Oncology, Radiology, and Nuclear Medicine, Erasmus Medical Center, Rotterdam, The Netherlands. 7. Department of Radiology, Weill Cornell Medicine, New York, New York. 8. Department of Nuclear Medicine, Royal Marsden NHS Foundation Trust, Sutton, United Kingdom. 9. Department of Medical Physics, Memorial Sloan Kettering Cancer Center, New York, New York. 10. Monash University and Eastern Health, Eastern Health Clinical School, Box Hill, Australia. 11. Department of Medical Oncology, Olivia Newton-John Cancer Research Institute, Austin Hospital, Melbourne, Victoria, Australia. 12. Department of Molecular Imaging and Therapy, University of Melbourne, Heidelberg, Victoria, Australia. 13. Department of Medicine, Memorial Sloan Kettering Cancer Center, New York, New York; and. 14. Department of Medicine, Weill Cornell Medicine, New York, New York.
Abstract
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 (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 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 (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 18F-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). 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. SUVAUC,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, SUVSHBG could potentially be used as an even simpler method to quantify 18F-FDHT uptake when less complex scanning protocols and accuracy are required.
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 (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 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 (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 18F-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). 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. SUVAUC,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, SUVSHBG could potentially be used as an even simpler method to quantify 18F-FDHT uptake when less complex scanning protocols and accuracy are required.
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