Bisphosphonate Bone Imaging Agent [68Ga]Ga-P15-041 for Evaluating Skeletal Metastases in Prostate Cancer

Background: Accurate diagnosis of bone metastases in prostate cancer is essential for staging, prognosis, and treatment. Although PSMA PET/CT is highly effective, complementary imaging is needed to clarify indeterminate lesions. The novel bisphosphonate-based agent [ 68 Ga]Ga-P15-041 shows superior diagnostic accuracy over conventional SPECT imaging, indicating its potential as an auxiliary diagnostic tool. This study explores its role in detecting and assessing prostate cancer bone metastases. Patients and Methods: This prospective study enrolled 35 patients with prostate cancer and skeletal metastases, who underwent both [ 68 Ga]Ga-P15-041 and [ 68 Ga]Ga-PSMA-11 PET/CT within 1 week. Lesions detected by [ 68 Ga]Ga-PSMA-11 PET/CT were classified using Prostate-specific Membrane Antigen Reporting and Data System 2.0. Results: [ 68 Ga]Ga-P15-041 PET/CT detected more lesions than [ 68 Ga]Ga-PSMA-11 PET/CT (525 vs 509, P < 0.001) and demonstrated significantly higher tracer uptake, with a mean SUV of 20.73 ± 14.67 compared with 11.13 ± 8.12 ( P < 0.0001). It detected significantly more osteoblastic lesions (504 vs 391, P < 0.0001). In addition, this study established the Reporting and Data System for [ 68 Ga]Ga-P15-041 (P15-041-RADS), which classifies prostate cancer bone metastases into 5 categories based on SUV max and morphologic changes. P15-041-RADS reclassified 85.71% of Prostate-specific Membrane Antigen Reporting and Data System category 3 lesions and 95.00% of 5T lesions into higher-confidence categories, offering improved diagnostic clarity. Limitations include small sample size and lack of pathologic gold standards. Conclusions: [ 68 Ga]Ga-P15-041 PET/CT is a promising and accessible bone imaging agent that could complement [ 68 Ga]Ga-PSMA-11 PET/CT in the diagnosis and classification of bone metastases in prostate cancer.