Purpose <p>The aim of this study was to evaluate the diagnostic performance of [⁶⁸Ga]Ga-DOTA-IBA PET/CT in the evaluation of bone metastases in metastatic prostate cancer patients scheduled for radionuclide therapy compared to [⁶⁸Ga]Ga-PSMA-11 PET/CT.</p> Methods <p>The intensity of tracer accumulation in pathological bone lesions on [⁶⁸Ga]Ga-DOTA-IBA PET/CT and [⁶⁸Ga]Ga-PSMA-11 PET/CT was measured as the maximum standardized uptake value (SUV_max) and compared to the background activity of normal bone. A lesion-based comparison was used to calculate the performance of both tracers. In addition, SUV_max of PET-positive bone lesions were analyzed in relation to morphologic features on CT.</p> Results <p>A total of 14 patients were included in this study. In contrast to 581 PET-positive lesions suggestive of bone metastases on [⁶⁸Ga]Ga-DOTA-IBA PET/CT, 505 of the lesions were also judged positive on [⁶⁸Ga]Ga-PSMA-11 PET/CT. The intensity of tracer accumulation in pathological skeletal lesions was significantly higher on [⁶⁸Ga]Ga-DOTA-IBA PET/CT compared to [⁶⁸Ga]Ga-PSMA-11 PET/CT. Background activity of normal bone was lower on [⁶⁸Ga]Ga-PSMA-11 PET/CT, with a median SUV_max of 0.567 compared to 0.849 on [⁶⁸Ga]Ga-DOTA-IBA PET/CT. Based on morphologic lesion characterization on CT, [⁶⁸Ga]Ga-DOTA-IBA PET/CT revealed median SUV_max values of 10.42 for osteosclerotic, 17.28 for osteolytic, and 11.38 for lesions not visible on CT, whereas on [⁶⁸Ga]Ga-PSMA-11 PET/CT, median SUV_max values of 8.68 for osteosclerotic, 19.38 for osteolytic, and 6.10 for lesions not seen on CT were measured. The intensity of tracer accumulation between [⁶⁸Ga]Ga-DOTA-IBA and [⁶⁸Ga]Ga-PSMA-11 PET/CT was significantly higher in osteosclerotic (<i>p</i> = 0.001) and lesions not visible on CT (<i>p</i> &lt; 0.001).</p> Conclusion <p>In comparison to [⁶⁸Ga]Ga-PSMA-11 PET/CT, [⁶⁸Ga]Ga-DOTA-IBA PET/CT is a comparable imaging modality in metastatic prostate cancer patients scheduled for radionuclide therapy. Our study indicates that [⁶⁸Ga]Ga-PSMA-11 PET/CT could be combined with [⁶⁸Ga]Ga-DOTA-IBA PET/CT in prostate cancer patients with bone metastases for evaluation prior to radionuclide therapy.</p> Trial registration <p>ChiCTR, ChiCTR2200064487. Registered 10 October 2022, <a href="https://www.chictr.org.cn">https://www.chictr.org.cn</a>, ChiCTR2200064487.</p>