Dual-tracer ¹⁸ F-FDG and ⁶⁸ Ga-DPI-4452 PET revealed distinct features of synchronous multiple renal cell carcinomas

A 66-year-old male presented with gross hematuria and a left renal mass. ¹⁸ F-FDG PET/CT revealed an FDG-avid mass in the mid-pole of the left kidney with renal vein tumor thrombus. The patient was subsequently enrolled in a clinical trial evaluating the carbonic anhydrase IX (CAIX)-targeted tracer ⁶⁸ Ga-DPI-4452 for renal tumor characterization and underwent ⁶⁸ Ga-DPI-4452 PET/MR. The FDG-avid lesions did not show increased ⁶⁸ Ga-DPI-4452 uptake, whereas a previously underappreciated upper-pole nodule—which was FDG-negative—demonstrated intense ⁶⁸ Ga-DPI-4452 uptake. Radical nephrectomy confirmed synchronous multiple primary renal cell carcinomas: the mid-pole mass was fumarate hydratase (FH)-deficient renal cell carcinoma (RCC), and the upper-pole lesion was clear cell RCC (ccRCC). This case suggests that dual-tracer PET may provide complementary molecular information in selected complex renal tumors and underscores the importance of interpreting CAIX-targeted imaging in the context of lesional CAIX heterogeneity.