18 F F-NYM124 for safety, imaging, and dosimetry in patients with indeterminate renal masses.

e16513 Background: With limitations of conventional imaging and biopsy, accurate, non-invasive techniques to detect in patients with primary and metastatic clear cell renal cell carcinoma (ccRCC) remain an unmet need. Carbonic anhydrase IX (CAIX) is a tumour antigen highly expressed in ccRCC. NYM124 is a new-generation CAIX targeting small molecule that can be labeled with 1 8 F. Here, 18 F F-NYM124 imaging characteristics, dosimetry, and safety were assessed in 2 patients with ccRCC. Methods: Patients with indeterminate renal masses underwent whole-body PET/CT at 1 h, 3 h, and 5 h after 18 F F-NYM124 administration, and patients also had 18 F-FDG PET/CT. Determination of tumor lesions was based on SUV max and SUV mean . Regions of interest were drawn on PET/CT images over critical organs and tumor lesions to generate time–activity curves, calculate tumor-to-background ratios per time point, and assess radioactivity residence times. Dosimetry assessments were based on time–activity curves and time-integrated activity coefficients to determine effective dose and absorbed dose per organ. Safety and tolerability were assessed up to 7 d after 18 F F-NYM124 administration. Results: The administered 18 F F-NYM124 activities were 9.4 mCi and 8.4 mCi. Tumor uptake was observed at all time points (1-5 h). One hour was chosen as the optimal time point. Across 4 lesions, the SUV max at 1 h after administration ranged from 25.3 to 211.5 (Mean±SD, 90.5±83.2), which was significantly higher than that of 18 F-FDG (2.8±1.4). The tumor-to-background-pool ratio was also higher (8.7±4.3 vs. 1.4±0.2). Intensive uptake was noted in the stomach, kidney, and pancreas, with SUV max of 44.2, 21.9 and 14.6, respectively. Substantial uptake was also noted in the intestine, whereas the brain did not show significant tracer accumulation, and mild uptake was observed in the choroid plexus. The investigators also found mild symmetrical uptake in the epididymis, which is consistent with physiological CAIX expression in this organ. OLINDA dosimetry estimates were calculated for 14 organs. Those with the highest mean absorbed doses included the kidney (0.104 mGy/MBq), pancreas (0.083 mGy/MBq) and stomach wall (0.062 mGy/MBq) with a mean whole-body effective dose of 0.018 mSv/MBq. Absorbed doses in the brain, thyroid and red marrow were low. The total-body residence times of radioactivity measured in the two patients after 18 F-NYM124 administration were 2.1 h and 2.4 h, demonstrating rapid systemic clearance of the tracer. No clinically significant toxicity was observed. Conclusions: Taken together with its reassuring dosimetry profile, 18 F F-NYM124 showed exceptional tumor uptake in patients with clear cell renal cell carcinoma, with high tumor-to-background ratios and no significant adverse events, suggesting potential diagnostic and patient selection applications.