{"entity":{"id":"idea-caix-theranostics","kind":"idea","name":"CAIX theranostics: 89Zr-girentuximab PET and 177Lu/225Ac-girentuximab therapy","aka":[],"tldr":"Almost every clear-cell kidney cancer carries the CAIX protein. Image it with one radioactive antibody, then treat with the same antibody carrying a therapeutic isotope.","summary":"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.","asOf":"2026-09-07","links":[{"label":"Shuch et al., ZIRCON: 89Zr-girentuximab PET-CT imaging of clear-cell renal cell carcinoma (Lancet Oncology 2024)","url":"https://doi.org/10.1016/S1470-2045(24)00402-9"}],"tags":[],"related":[],"cancers":["rcc"],"sections":[],"technologies":["caix-pet","radioligand-therapy","targeted-alpha-therapy","radioimmunotherapy"],"targets":["hif2a"],"drugs":[],"companies":["telix"],"institutions":[],"pathways":[],"terms":[],"trials":[],"people":[],"bottlenecks":[],"keyPapers":["paper-shuch-lancet-oncol"],"journals":[],"dependsOn":[],"notes":[],"hypothesis":"177Lu- or 225Ac-girentuximab produces objective responses in ≥25% of heavily pretreated clear-cell RCC patients selected by CAIX PET, and synergises with PD-1 blockade.","rationale":"Stable antigen, theranostic pairing proven in prostate cancer (PSMA), and radiation-induced immunogenic cell death in an immunotherapy-responsive tumour.","test":"Randomised phase 2 of 177Lu-girentuximab + nivolumab vs nivolumab after IO-TKI progression, PET-selected.","maturity":"early-clinical"},"route":"/ideas/idea-caix-theranostics/","neighbours":{"cancer":[{"id":"rcc","kind":"cancer","name":"Renal cell carcinoma","route":"/cancers/rcc/"}],"technology":[{"id":"caix-pet","kind":"technology","name":"CAIX PET (89Zr-girentuximab)","route":"/technologies/caix-pet/"},{"id":"radioimmunotherapy","kind":"technology","name":"Radio-antibody & radio-ADC","route":"/technologies/radioimmunotherapy/"},{"id":"radioligand-therapy","kind":"technology","name":"Radioligand therapy (beta emitters)","route":"/technologies/radioligand-therapy/"},{"id":"targeted-alpha-therapy","kind":"technology","name":"Targeted alpha therapy","route":"/technologies/targeted-alpha-therapy/"}],"target":[{"id":"hif2a","kind":"target","name":"HIF-2α","route":"/targets/hif2a/"}],"company":[{"id":"telix","kind":"company","name":"Telix Pharmaceuticals","route":"/companies/telix/"}],"paper":[{"id":"paper-shuch-lancet-oncol","kind":"paper","name":"[ 89 Zr]Zr-girentuximab for PET-CT imaging of clear-cell renal cell carcinoma: a prospective, open-label, multicentre, phase 3 trial","route":"/key-papers/paper-shuch-lancet-oncol/"}]}}