Hebert Alberto Vargas1, Gem M Kramer2, Andrew M Scott3,4, Andrew Weickhardt5, Andreas A Meier6, Nicole Parada7, Bradley J Beattie8, John L Humm8, Kevin D Staton6, Pat B Zanzonico6, Serge K Lyashchenko6, Jason S Lewis6,9, Maqsood Yaqub2, Ramon E Sosa6, Alfons J van den Eertwegh10, Ian D Davis11, Uwe Ackermann12, Kunthi Pathmaraj12, Robert C Schuit2, Albert D Windhorst2, Sue Chua13, Wolfgang A Weber6,9, Steven M Larson6,9, Howard I Scher7,14, Adriaan A Lammertsma2, Otto S Hoekstra2, Michael J Morris7,14. 1. Department of Radiology, Memorial Sloan Kettering Cancer Center, New York, New York vargasah@mskcc.org. 2. Department of Radiology and Nuclear Medicine, VU University Medical Centre, Amsterdam, The Netherlands. 3. Department of Molecular Imaging and Therapy, The University of Melbourne, Heidelberg, Victoria, Australia. 4. Department of Medicine, The University of Melbourne, Olivia Newton-John Cancer Research Institute, and La Trobe University, Austin Hospital, Heidelberg, Victoria, Australia. 5. Department of Medical Oncology, Olivia Newton-John Cancer Research Institute, Austin Hospital, Melbourne, Victoria, Australia. 6. Department of Radiology, Memorial Sloan Kettering Cancer Center, New York, New York. 7. Department of Medicine, Memorial Sloan Kettering Cancer Center, New York, New York. 8. Department of Medical Physics, Memorial Sloan Kettering Cancer Center, New York, New York. 9. Department of Radiology, Weill Cornell Medicine, New York, New York. 10. Department of Medical Oncology, VU University Medical Centre, Amsterdam, The Netherlands. 11. Monash University and Eastern Health, Eastern Health Clinical School, Box Hill, Australia. 12. Department of Nuclear Medicine and Centre for PET, Austin Health, Heidelberg, Victoria, Australia. 13. Department of Nuclear Medicine, Royal Marsden NHS Foundation Trust, Sutton, United Kingdom; and. 14. Department of Medicine, Weill Cornell Medicine, New York, New York.
Abstract
18F-fluorodihydrotestosterone (18F-FDHT) is a radiolabeled analog of the androgen receptor's primary ligand that is currently being credentialed as a biomarker for prognosis, response, and pharmacodynamic effects of new therapeutics. As part of the biomarker qualification process, we prospectively assessed its reproducibility and repeatability in men with metastatic castration-resistant prostate cancer. Methods: We conducted a prospective multiinstitutional study of metastatic castration-resistant prostate cancer patients undergoing 2 (test/retest) 18F-FDHT PET/CT scans on 2 consecutive days. Two independent readers evaluated all examinations and recorded SUVs, androgen receptor-positive tumor volumes, and total lesion uptake for the most avid lesion detected in each of 32 predefined anatomic regions. The relative absolute difference and reproducibility coefficient (RC) of each metric were calculated between the test and retest scans. Linear regression analyses, intraclass correlation coefficients (ICCs), and Bland-Altman plots were used to evaluate repeatability of 18F-FDHT metrics. The coefficient of variation and ICC were used to assess interobserver reproducibility. Results: Twenty-seven patients with 140 18F-FDHT-avid regions were included. The best repeatability among 18F-FDHT uptake metrics was found for SUV metrics (SUVmax, SUVmean, and SUVpeak), with no significant differences in repeatability among them. Correlations between the test and retest scans were strong for all SUV metrics (R 2 ≥ 0.92; ICC ≥ 0.97). The RCs of the SUV metrics ranged from 21.3% (SUVpeak) to 24.6% (SUVmax). The test and retest androgen receptor-positive tumor volumes and TLU, respectively, were highly correlated (R 2 and ICC ≥ 0.97), although variability was significantly higher than that for SUV (RCs > 46.4%). The prostate-specific antigen levels, Gleason score, weight, and age did not affect repeatability, nor did total injected activity, uptake measurement time, or differences in uptake time between the 2 scans. Including the most avid lesion per patient, the 5 most avid lesions per patient, only lesions 4.2 mL or more, only lesions with an SUV of 4 g/mL or more, or normalizing of SUV to area under the parent plasma activity concentration-time curve did not significantly affect repeatability. All metrics showed high interobserver reproducibility (ICC > 0.98; coefficient of variation < 0.2%-10.8%). Conclusion: Uptake metrics derived from 18F-FDHT PET/CT show high repeatability and interobserver reproducibility.
18F-fluorodihydrotestosterone (18F-FDHT) is a radiolabeled analog of the androgen receptor's primary ligand that is currently being credentialed as a biomarker for prognosis, response, and pharmacodynamic effects of new therapeutics. As part of the biomarker qualification process, we prospectively assessed its reproducibility and repeatability in men with metastatic castration-resistant prostate cancer. Methods: We conducted a prospective multiinstitutional study of metastatic castration-resistant prostate cancerpatients undergoing 2 (test/retest) 18F-FDHT PET/CT scans on 2 consecutive days. Two independent readers evaluated all examinations and recorded SUVs, androgen receptor-positive tumor volumes, and total lesion uptake for the most avid lesion detected in each of 32 predefined anatomic regions. The relative absolute difference and reproducibility coefficient (RC) of each metric were calculated between the test and retest scans. Linear regression analyses, intraclass correlation coefficients (ICCs), and Bland-Altman plots were used to evaluate repeatability of 18F-FDHT metrics. The coefficient of variation and ICC were used to assess interobserver reproducibility. Results: Twenty-seven patients with 140 18F-FDHT-avid regions were included. The best repeatability among 18F-FDHT uptake metrics was found for SUV metrics (SUVmax, SUVmean, and SUVpeak), with no significant differences in repeatability among them. Correlations between the test and retest scans were strong for all SUV metrics (R 2 ≥ 0.92; ICC ≥ 0.97). The RCs of the SUV metrics ranged from 21.3% (SUVpeak) to 24.6% (SUVmax). The test and retest androgen receptor-positive tumor volumes and TLU, respectively, were highly correlated (R 2 and ICC ≥ 0.97), although variability was significantly higher than that for SUV (RCs > 46.4%). The prostate-specific antigen levels, Gleason score, weight, and age did not affect repeatability, nor did total injected activity, uptake measurement time, or differences in uptake time between the 2 scans. Including the most avid lesion per patient, the 5 most avid lesions per patient, only lesions 4.2 mL or more, only lesions with an SUV of 4 g/mL or more, or normalizing of SUV to area under the parent plasma activity concentration-time curve did not significantly affect repeatability. All metrics showed high interobserver reproducibility (ICC > 0.98; coefficient of variation < 0.2%-10.8%). Conclusion: Uptake metrics derived from 18F-FDHT PET/CT show high repeatability and interobserver reproducibility.
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