Reproducibility and Repeatability of Semiquantitative 18F-Fluorodihydrotestosterone Uptake Metrics in Castration-Resistant Prostate Cancer Metastases: A Prospective Multicenter Study

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 (SUV_max, SUV_mean, and SUV_peak), 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% (SUV_peak) to 24.6% (SUV_max). 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.

Keywords: FDHT; PET; prostate cancer; repeatability; reproducibility.

FIGURE 1.

Box plots of percentage differences on lesion level between test and retest scans for several quantitative uptake values. Effect of normalizing to AUCpp is shown.

FIGURE 2.

Bland–Altman plots showing repeatability SUV_max on lesion (A) and patient (B) level. Blue = center 1; red = center 2; green = center 3.

FIGURE 3.

Bland–Altman plots showing repeatability of SUV_peak on lesion (A) and patient (B) level. Blue = center 1; red = center 2; green = center 3.

FIGURE 4.

Bland–Altman plots showing influence of ARTV on repeatability of SUV_max on lesion level. Log scale is used on x-axis. Blue = center 1; red = center 2; green = center 3.

FIGURE 5.

Bland–Altman plots showing repeatability of TLU (A and B) and ARTV (C and D) on lesion (A and C) and patient (B and D) level. For TLU and lesion-level ARTV: log scale is used on x-axis. Blue = center 1; red = center 2; green = center 3.

FIGURE 6.

Box plots of percentage differences on patient level between test and retest scans for several quantitative uptake values. Effect of normalizing to AUC is shown.

FIGURE 7.

Scatterplot showing effect of differences in uptake time (mins) between test and retest scans on differences in uptake at patient level. Similar patterns are seen for other quantitative uptake metrics. Blue = center 1; red = center 2; green = center 3.