Diagnostic Performance of [68Ga]Ga-DPI-4452 PET/CT in Patients with Clear Cell Renal Cell Carcinoma: A Prospective Trial.

Preoperative identification and staging of clear cell renal cell carcinoma (ccRCC) are challenging. We prospectively evaluated [68Ga]Ga-DPI-4452, a carbonic anhydrase IX (CAIX)-targeted tracer, for same-day PET/CT. Methods: Adults with suspected renal masses scheduled for surgery or biopsy underwent [68Ga]Ga-DPI-4452 PET/CT. Histopathology or composite follow-up served as the reference standard. Results: Thirty patients were enrolled (23 with ccRCC; 7 with non-ccRCC/benign lesions). No tracer-related adverse events occurred. [68Ga]Ga-DPI-4452 PET/CT identified primary ccRCC with 100% sensitivity and 85.7% specificity. For extrarenal metastases, [68Ga]Ga-DPI-4452 PET/CT achieved a sensitivity of 97.7% and detected 82.6% more lesions than did conventional imaging. Tracer uptake was strongly correlated with tissue CAIX H-score (r = 0.83, P < 0.0001). Beyond primary lesions, [68Ga]Ga-DPI-4452 PET/CT detected 20 metastases missed by conventional imaging, resulting in a net increase of 19 lesions after accounting for 1 PET-negative hepatic metastasis, and provided complementary biologic characterization of venous thrombi viability. Conclusion: [68Ga]Ga-DPI-4452 PET/CT was well-tolerated and showed promising performance in identifying primary ccRCC and detecting metastatic disease, while also reflecting tissue CAIX expression.