CAIX theranostics: 89Zr-girentuximab PET and 177Lu/225Ac-girentuximab therapy

Nearly every clear-cell renal cell carcinoma expresses carbonic anhydrase IX as a direct consequence of VHL loss, so the antigen is near-universal and stable. This theranostic idea images it with 89Zr-girentuximab PET, validated for diagnosis in ZIRCON, and then treats with the same antibody carrying 177Lu for beta emission or 225Ac for targeted alpha therapy. The rationale combines a stable target, the PSMA precedent in prostate cancer, and radiation-induced immunogenic cell death in a cancer that already responds to immunotherapy. STARLITE-1 and STARLITE-2 are testing 177Lu-girentuximab with nivolumab or cabozantinib, and the proposed test is a randomised phase 2 of 177Lu-girentuximab plus nivolumab versus nivolumab alone; Telix Pharmaceuticals is the linked company.