ArticleEuropean journal of nuclear medicine and molecular imaging2026
CAIX-targeted radiotracer for diagnosis and monitoring VEGFR-TKI response in clear cell renal cell carcinoma.
Article in European journal of nuclear medicine and molecular imaging, 2026. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Not yet cited in PubMed.
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Abstract
purposeCarbonic anhydrase IX (CAIX) represents a promising target for molecular imaging of clear cell renal cell carcinoma (ccRCC). We designed three radiotracers targeting CAIX to improve the diagnostic value of imaging by increasing tumor uptake and the liver excretion pathway. We also aimed to demonstrate the feasibility of applying small-molecule radiotracers in VEGFR-TKI efficacy monitoring in renal cancer.
methodsThis study developed three novel CAIX-targeting radiotracers, which were evaluated in vitro and in vivo; The study also included 8 patients with ccRCC, all of whom had paired [68Ga]Ga-NOTA-FZCI-3 PET/CT and [18F]-FDG PET/CT. The diagnostic efficacies of these two PET tracers were compared. Moreover, VEGFR-TKI efficacy monitoring experiments using [68Ga]Ga-NOTA-FZCI-3 was conducted on OS-RC-2 models.
resultsThree radiotracers showed that different liver/renal accumulations were better correlated with factors including distinct plasma protein binding abilities. [68Ga]Ga-NOTA-FZCI-3, primarily cleared through the hepatobiliary system in patients, demonstrated a higher SUVmax of renal lesions (median, 13.10 vs. 3.10, n = 4; *P = 0.04) and superior tumor-to-muscle ratio of metastatic lesions (9.25 ± 5.10 vs.3.64 ± 2.11, n = 16; **P = 0.004) to [18F]-FDG in a prospective cohort with 8 ccRCC patients. In VEGFR-TKI efficacy monitoring experiments, [68Ga]Ga-NOTA-FZCI-3 showed markedly decreased tumor radiotracer uptake throughout treatment. Moreover, VEGFR-AKT-mTOR pathway inhibition and CAIX downregulation in the treatment group confirmed that [68Ga]Ga-NOTA-FZCI-3 PET/CT is a viable strategy for monitoring TKI efficacy in renal cell cancer.
conclusion[68Ga]Ga-NOTA-FZCI-3 is a promising radiotracer for improving diagnosis, staging, and VEGFR-TKI efficacy monitoring in ccRCC.
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