TY - JOUR
T1 - Reproducibility and Repeatability of Semiquantitative 18F-Fluorodihydrotestosterone Uptake Metrics in Castration-Resistant Prostate Cancer Metastases
T2 - A Prospective Multicenter Study
AU - Vargas, Hebert Alberto
AU - Kramer, Gem M.
AU - Scott, Andrew M.
AU - Weickhardt, Andrew
AU - Meier, Andreas A.
AU - Parada, Nicole
AU - Beattie, Bradley J.
AU - Humm, John L.
AU - Staton, Kevin D.
AU - Zanzonico, Pat B.
AU - Lyashchenko, Serge K.
AU - Lewis, Jason S.
AU - Yaqub, Maqsood
AU - Sosa, Ramon E.
AU - van den Eertwegh, Alfons J.
AU - Davis, Ian D.
AU - Ackermann, Uwe
AU - Pathmaraj, Kunthi
AU - Schuit, Robert C.
AU - Windhorst, Albert D.
AU - Chua, Sue
AU - Weber, Wolfgang A.
AU - Larson, Steven M.
AU - Scher, Howard I.
AU - Lammertsma, Adriaan A.
AU - Hoekstra, Otto S.
AU - Morris, Michael J.
PY - 2018
Y1 - 2018
N2 - 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 18FFDHT- 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 (R2 ≥ 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 (R2 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.
AB - 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 18FFDHT- 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 (R2 ≥ 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 (R2 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.
UR - https://www.scopus.com/inward/record.uri?partnerID=HzOxMe3b&scp=85054100127&origin=inward
UR - https://www.ncbi.nlm.nih.gov/pubmed/29626121
U2 - https://doi.org/10.2967/jnumed.117.206490
DO - https://doi.org/10.2967/jnumed.117.206490
M3 - Article
C2 - 29626121
SN - 0161-5505
VL - 59
SP - 1516
EP - 1523
JO - Journal of nuclear medicine
JF - Journal of nuclear medicine
IS - 10
ER -