A prospective multicenter study reported that CAIX-targeted [68Ga]Ga-DPI-4452 PET/CT detected 97.9% of clear-cell renal cell carcinoma lesions, compared with 47.1% detection using 18F-FDG PET/CT. The findings position CAIX imaging as a substantially higher-sensitivity approach for identifying tumor lesions in its target population. The study design emphasized prospective evaluation and lesion detection rates across imaging comparators, supporting CAIX as an imaging biomarker tied to clear-cell biology. Investigators’ results could influence downstream staging and treatment planning workflows for renal cancer imaging. For developers of molecular imaging agents, the contrast in lesion detection performance provides clear comparative motivation for trial expansion and potential regulatory review pathways.