TY - JOUR
T1 - Assessment of simplified methods for quantification of 18F-FDHT uptake in patients with metastatic castration-resistant prostate cancer
AU - Kramer, Gerbrand M.
AU - Yaqub, Maqsood
AU - Vargas, Herbert A.
AU - Schuit, Robert C.
AU - Windhorst, Albert D.
AU - van den Eertwegh, Alfonsus J. M.
AU - van der Veldt, Astrid A. M.
AU - Bergman, Andries M.
AU - Burnazi, Eva M.
AU - Lewis, Jason S.
AU - Chua, Sua
AU - Staton, Kevin D.
AU - Beattie, Brad J.
AU - Humm, John L.
AU - Davis, Ian D.
AU - Weickhardt, Andrew J.
AU - Scott, Andrew M.
AU - Morris, Michael J.
AU - Hoekstra, Otto S.
AU - Lammertsma, Adriaan A.
PY - 2019/9/1
Y1 - 2019/9/1
N2 - 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 Ki results (R2 5 0.98). Patlak Ki and SUVAUC,PP showed an excellent correlation (R2 . 0.9). SUVBW showed a moderate correlation to Ki (R2 5 0.70, presumably due to fast 18F-FDHT metabolism. When calculating SUVSHBG, correlation to Ki improved (R2 5 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.
AB - 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 Ki results (R2 5 0.98). Patlak Ki and SUVAUC,PP showed an excellent correlation (R2 . 0.9). SUVBW showed a moderate correlation to Ki (R2 5 0.70, presumably due to fast 18F-FDHT metabolism. When calculating SUVSHBG, correlation to Ki improved (R2 5 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.
UR - https://www.scopus.com/inward/record.uri?partnerID=HzOxMe3b&scp=85069923352&origin=inward
UR - https://www.ncbi.nlm.nih.gov/pubmed/30850488
U2 - https://doi.org/10.2967/jnumed.118.220111
DO - https://doi.org/10.2967/jnumed.118.220111
M3 - Article
C2 - 30850488
SN - 0161-5505
VL - 60
SP - 1221
EP - 1227
JO - Journal of nuclear medicine
JF - Journal of nuclear medicine
IS - 9
ER -