Preclinical and pilot clinical evaluation of a small-molecule carbonic anhydrase IX targeting PET tracer in clear cell renal cell carcinoma

Clear cell renal cell carcinoma (ccRCC) highly expresses carbonic anhydrase IX (CAIX). The purpose of this study was to evaluate ⁶⁸Ga-NY104, a small-molecule CAIX-targeting PET agent, in tumor models of ccRCC and patients diagnosed with confirmed, or suspicious, ccRCC.

The in vivo and ex vivo biodistribution of ⁶⁸Ga-NY104 was investigated in CAIX-positive OS-RC-2 xenograft-bearing models. The binding of the tracer was further validated using autoradiography for human ccRCC samples. In addition, three patients with confirmed or suspicious ccRCC were studied.

NY104 can be labeled with high radiochemical yield and purity. It quickly cleared through kidney with α-half-life of 0.15 h. Discernible uptake is noted in the heart, lung, liver, stomach, and kidney. The OS-RC-2 xenograft demonstrated intense uptake 5 min after injection and gradually increased until 3 h after injection with ID%/g of 29.29 ± 6.82. Significant binding was detected using autoradiography on sections of human ccRCC tumor. In the three patients studied, ⁶⁸Ga-NY104 was well-tolerated and no adverse events were reported. Substantial accumulation was observed in both primary and metastatic lesions in patient 1 and 2 with SUVmax of 42.3. Uptake in the stomach, pancreas, intestine, and choroid plexus was noted. The lesion in third patient was correctly diagnosed as non-metastatic for negative ⁶⁸Ga-NY104 uptake.

⁶⁸Ga-NY104 can efficiently and specifically bind to CAIX. Given the pilot nature of our study, future clinical studies are warranted to evaluate ⁶⁸Ga-NY104 for detection of CAIX-positive lesions in patients with ccRCC.