Diagnostic performance, safety, and biodistribution of [ 68 Ga]Ga-OncoCAIX for PET/CT imaging: A first-in-human phase I clinical trial in clear cell renal cell carcinoma.

3075 Background: Conventional imaging techniques are routinely used in clear cell renal cell carcinoma (ccRCC). However, their ability to accurately characterise tumour biology and stage the disease remains limited. An attractive target for theranostic applications is represented by carbonic anhydrase IX (CAIX), which is overexpressed in ccRCC. [⁶⁸Ga]Ga-OncoCAIX is a novel small-molecule radiopharmaceutical for positron emission tomography (PET) imaging. The compound has been discovered by DNA-Encoded Chemical Libraries and designed to selectively bind to CAIX, allowing for tumour-specific uptake and favourable biodistribution in preclinical models. This multicentre, prospective, phase I study provides the first-in-human assessment of [⁶⁸Ga]Ga-OncoCAIX PET/CT in patients with kidney lesions. Methods: Twenty patients with suspected primary or recurrent ccRCC based on conventional imaging were planned for enrolment in the study. Each patient received a single intravenous injection of [⁶⁸Ga]Ga-OncoCAIX. PET/CT acquisitions were performed at 0, 10, 60 and 120 minutes after the injection with multiple blood and urine samples collections for pharmacokinetic and dosimetric analysis. Adverse events were recorded and graded according to CTCAE v5.0. Where available, PET findings were correlated with histopathology. Results: Twenty patients were included. Seventeen patients were evaluated for incidentally detected renal masses, and three for suspected recurrence identified on CT or MRI. [⁶⁸Ga]Ga-OncoCAIX was well tolerated, with no drug-related AEs reported. The tracer demonstrated mixed renal and hepatic clearance, favourable biodistribution, and low background activity in healthy tissues, including the kidneys. Physiological uptake was mainly observed in the gastrointestinal tract, particularly the stomach. PET-positive lesions showed rapid and selective tumour uptake shortly after injection, with increasing signal intensity at 60 and 120 minutes. Eight patients had positive PET findings, eleven scans were negative and one patient presented a lesion with mild tracer uptake. Available histopathological confirmation showed concordance with PET results, including three PET-positive ccRCCs, three PET-negative oncocytomas, and one PET-negative chromophobe RCC; the one lesion with mild tracer uptake corresponded to a papillary RCC with mild CAIX expression on histology. Dosimetric analyses are ongoing. Conclusions: [⁶⁸Ga]Ga-OncoCAIX shows an excellent safety profile and favourable biodistribution, as well as promising tumour-targeting properties in ccRCC lesions. These preliminary findings support its potential role for the detection and characterisation of ccRCC. Complete data on histopathology will confirm the diagnostic accuracy and potential clinical utility in patients with suspected ccRCC. Clinical trial information: NCT06840548 .