Based on data from the phase III SPOTLIGHT study, the PPV of bone uptake of 18F-flotufolastat on PET/CT in patients with recurrent prostate cancer was 63–80% across readers, comparable with the PPV of bone uptake of a previously FDA-approved 18F-labeled PSMA radiopharmaceutical. Evaluation of bone uptake should incorporate interpretive guidelines, clinical context, and cross-sectional imaging correlation.