68Ga-NY104

FDG PET/CT often underperforms in characterizing hyper-enhancing, FDG-non-avid renal masses. We present two cases illustrating the potential of 68Ga-NY104, a novel small-molecule tracer targeting carbonic anhydrase IX (CAIX), for this differential diagnosis. Both patients presented with a hyper-enhancing right renal mass suspicious for clear cell renal carcinoma (ccRCC) and subsequently underwent both 18F-FDG and 68Ga-NY104 PET/CT, with histopathology and CAIX immunohistochemistry (IHC) as the reference standard. On 18F-FDG, both lesions were non-avid (SUVmax 2.6 and 2.2, Tumor-to-Liver Ratio [TLR] 0.87 and 0.69, respectively). However, on 68Ga-NY104 PET/CT, Patient 1 (a 65-year-old man) showed intense, homogeneous uptake (SUVmax 26.0, TLR 4.64), while Patient 2 (a 67-year-old woman) showed negligible uptake (SUVmax 2.5, TLR 0.68). It was consistent with histopathology and IHC results that Patient 1 was CAIX-positive ccRCC, while Patient 2 was CAIX-negative hemangioma. Our preliminary cases suggest the potential utility of CAIX-targeted PET/CT imaging with 68Ga-NY104 in differentiating ccRCC from benign mimickers like renal hemangioma, which warrants further prospective evaluation.