Assessment of simplified methods for quantification of 18F-FDHT uptake in patients with metastatic castration-resistant prostate cancer

Gerbrand M. Kramer, Maqsood Yaqub, Herbert A. Vargas, Robert C. Schuit, Albert D. Windhorst, Alfonsus J. M. van den Eertwegh, Astrid A. M. van der Veldt, Andries M. Bergman, Eva M. Burnazi, Jason S. Lewis, Sua Chua, Kevin D. Staton, Brad J. Beattie, John L. Humm, Ian D. Davis, Andrew J. Weickhardt, Andrew M. Scott, Michael J. Morris, Otto S. Hoekstra, Adriaan A. Lammertsma

Research output: Contribution to journalArticleAcademicpeer-review

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 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.
Original languageEnglish
Pages (from-to)1221-1227
JournalJournal of Nuclear Medicine
Volume60
Issue number9
DOIs
Publication statusPublished - 1 Sep 2019

Cite this

Kramer, Gerbrand M. ; Yaqub, Maqsood ; Vargas, Herbert A. ; Schuit, Robert C. ; Windhorst, Albert D. ; van den Eertwegh, Alfonsus J. M. ; van der Veldt, Astrid A. M. ; Bergman, Andries M. ; Burnazi, Eva M. ; Lewis, Jason S. ; Chua, Sua ; Staton, Kevin D. ; Beattie, Brad J. ; Humm, John L. ; Davis, Ian D. ; Weickhardt, Andrew J. ; Scott, Andrew M. ; Morris, Michael J. ; Hoekstra, Otto S. ; Lammertsma, Adriaan A. / Assessment of simplified methods for quantification of 18F-FDHT uptake in patients with metastatic castration-resistant prostate cancer. In: Journal of Nuclear Medicine. 2019 ; Vol. 60, No. 9. pp. 1221-1227.
@article{c547d647a7064f7cbdb0747685a3cfcc,
title = "Assessment of simplified methods for quantification of 18F-FDHT uptake in patients with metastatic castration-resistant prostate cancer",
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 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.",
author = "Kramer, {Gerbrand M.} and Maqsood Yaqub and Vargas, {Herbert A.} and Schuit, {Robert C.} and Windhorst, {Albert D.} and {van den Eertwegh}, {Alfonsus J. M.} and {van der Veldt}, {Astrid A. M.} and Bergman, {Andries M.} and Burnazi, {Eva M.} and Lewis, {Jason S.} and Sua Chua and Staton, {Kevin D.} and Beattie, {Brad J.} and Humm, {John L.} and Davis, {Ian D.} and Weickhardt, {Andrew J.} and Scott, {Andrew M.} and Morris, {Michael J.} and Hoekstra, {Otto S.} and Lammertsma, {Adriaan A.}",
year = "2019",
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doi = "10.2967/jnumed.118.220111",
language = "English",
volume = "60",
pages = "1221--1227",
journal = "Journal of Nuclear Medicine",
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Kramer, GM, Yaqub, M, Vargas, HA, Schuit, RC, Windhorst, AD, van den Eertwegh, AJM, van der Veldt, AAM, Bergman, AM, Burnazi, EM, Lewis, JS, Chua, S, Staton, KD, Beattie, BJ, Humm, JL, Davis, ID, Weickhardt, AJ, Scott, AM, Morris, MJ, Hoekstra, OS & Lammertsma, AA 2019, 'Assessment of simplified methods for quantification of 18F-FDHT uptake in patients with metastatic castration-resistant prostate cancer' Journal of Nuclear Medicine, vol. 60, no. 9, pp. 1221-1227. https://doi.org/10.2967/jnumed.118.220111

Assessment of simplified methods for quantification of 18F-FDHT uptake in patients with metastatic castration-resistant prostate cancer. / Kramer, Gerbrand M.; Yaqub, Maqsood; Vargas, Herbert A.; Schuit, Robert C.; Windhorst, Albert D.; van den Eertwegh, Alfonsus J. M.; van der Veldt, Astrid A. M.; Bergman, Andries M.; Burnazi, Eva M.; Lewis, Jason S.; Chua, Sua; Staton, Kevin D.; Beattie, Brad J.; Humm, John L.; Davis, Ian D.; Weickhardt, Andrew J.; Scott, Andrew M.; Morris, Michael J.; Hoekstra, Otto S.; Lammertsma, Adriaan A.

In: Journal of Nuclear Medicine, Vol. 60, No. 9, 01.09.2019, p. 1221-1227.

Research output: Contribution to journalArticleAcademicpeer-review

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.

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UR - https://www.ncbi.nlm.nih.gov/pubmed/30850488

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DO - 10.2967/jnumed.118.220111

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EP - 1227

JO - Journal of Nuclear Medicine

JF - Journal of Nuclear Medicine

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