Castration-Resistant Prostate Cancer Bone Metastasis Response Measured by F-18-Fluoride PET After Treatment with Dasatinib and Correlation with Progression-Free Survival: Results from American College of Radiology Imaging Network 6687

F-18-fluoride PET quantitatively images bone metabolism and may serve as a pharmacodynamic assessment for systemic therapy such as dasatinib, a potent SRC kinase inhibitor, with activity in bone. Methods: This was an imaging companion trial (American College of Radiology Imaging Network [ACRIN] 6687) to a multicenter metastatic castration-resistant prostate cancer (CRPC) tissue biomarker-guided therapeutic trial (NCT00918385). Men with bone metastatic CRPC underwent F-18-fluoride PET before and 12 weeks after initiation of dasatinib (100 mg daily). Dynamic imaging was performed over a 15-cm field of view for trial assessments. The primary endpoint was to determine whether changes in F-18-fluoride incorporation in tumor and normal bone occurred in response to dasatinib. Other endpoints included differential effect of dasatinib between F-18-fluoride incorporation in tumor and normal bone, (18)Ffluoride transport in bone metastases, correlation with progressionfree survival (PFS), prostate-specific antigen, and markers of bone turnover. Results: Eighteen participants enrolled, and 17 underwent interpretable baseline F-18-fluoride PET imaging before initiation of dasatinib. Twelve of 17 patients underwent on-treatment PET imaging. Statistically significant changes in response to dasatinib were identified by the SUVmaxavg (average of maximum standardized uptake value [SUVmax] for up to 5 tumors within the dynamic field of view) in bone metastases (P = 0.0002), with a significant differential F-18-fluoride PET response between tumor and normal bone (P, 0.0001). Changes in F-18-fluoride incorporation in bone metastases had borderline correlation with PFS by SUVmaxavg (hazard ratio, 0.91; 95% confidence interval, 0.82-1.00; P = 0.056). Changes by SUVmaxavg correlated with bone alkaline phosphatase (P = 0.0014) but not prostate-specific antigen (P = 0.47). Conclusion: This trial provides evidence of the ability F-18-fluoride PET to delineate treatment response of dasatinib in CRPC bone metastases with borderline correlation with PFS.