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|Title:||Reproducibility and repeatability of semi-quantitative18F-fluorodihydrotestosterone (FDHT) uptake metrics in castration-resistant prostate cancer metastases: a prospective multi-center study.|
|Authors:||Vargas, Hebert Alberto;Kramer, Gem M;Scott, Andrew M;Weickhardt, Andrew J;Meier, Andreas A;Parada, Nicole;Beattie, Bradley J;Humm, John L;Staton, Kevin D;Zanzonico, Pat B;Lyashchenko, Serge K;Lewis, Jason S;Yaqub, Maqsood;Sosa, Ramon E;van den Eertwegh, Alfons J;Davis, Ian D;Ackermann, Uwe;Pathmaraj, Kunthi;Schuit, Robert C;Windhorst, Albert D;Chua, Sue;Weber, Wolfgang A;Larson, Steven M;Scher, Howard I;Lammertsma, Adriaan A;Hoekstra, Otto;Morris, Michael J|
|Affiliation:||Memorial Sloan Kettering Cancer Center, New York, New York, USA|
VU University Medical Centre..
The University of Melbourne..
Olivia Newton-John Cancer Research Institute, Austin Health, Heidelberg, Victoria, Australia
Eastern Health Clinical School - Monash University..
Austin Health, Heidelberg, Victoria, Australia
Royal Marsden NHS Foundation Trust..
|Citation:||Journal of nuclear medicine 2018; online first: 6 April|
|Abstract:||18 F-fluorodihydrotestosterone (18F-FDHT) is a radiolabeled analogue 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 (mCRPC).Methods:We conducted a prospective multi-institutional study of mCRPC patients undergoing two (test/re-test)18F-FDHT PET/CT scans on two consecutive days. Two independent readers evaluated all examinations and recorded standardized uptake values (SUVs), androgen receptor-positive tumor volumes (ARTV), and total lesion uptake (TLU) for the most avid lesion detected in each of 32 pre-defined anatomical regions. The relative absolute difference and reproducibility coefficient (RC) of each metric were calculated between the test and re-test scans. Linear regression analyses, intra-class correlation coefficients (ICC), and Bland-Altman plots were used to evaluate repeatability of18F-FDHT metrics. The coefficient of variation (COV) and ICC were used to assess inter-observer reproducibility.Results:Twenty-seven patients with 14018F-FDHT-avid regions were included. The best repeatability among18F-FDHT uptake metrics was found for SUV metrics (SUVmax, SUVmean, and SUVpeak), with no significant differences in repeatability found among them. Correlations between the test and re-test scans were strong for all SUV metrics (R2 ≥ 0.92; ICC ≥ 0.97). The RCs of the SUV metrics ranged from 21.3% for SUVpeak to 24.6% for SUVmaxThe test and re-test ARTV and TLU, respectively, were highly correlated (R2 and ICC ≥ 0.97), although variability was significantly higher than that for SUV (RCs > 46.4%). The PSA 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 two scans. Including the single most avid lesion per patient, the five most avid lesions per patient, only lesions ≥ 4.2 mL, only lesions with an SUV ≥ 4 g/mL, or normalizing of SUV to area under the parent plasma activity concentration-time curve did not significantly affect repeatability. All metrics showed high inter-observer reproducibility (ICC > 0.98; COV < 0.2-10.8%).Conclusion:18F-FDHT is a highly reproducible means of imaging mCRPC. Amongst18F-FDHT uptake metrics, SUV had the highest repeatability among the measures assessed. These performance characteristics lend themselves to further biomarker development and clinical qualification of the tracer.|
|Appears in Collections:||Journal articles|
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