A phase Ia study to estimate the radiochemical and radiation safety of ^68G a-NYM005, a radiolabeled carbonic anhydrase IX PET imaging agent for diagnosing, staging, and following patients with clear cell renal cell carcinoma.

e16508 Background: 68 Ga-NYM005, a first-in-class carbonic anhydrase IX (CAIX)–binding radiolabeled small-molecule, is a quantitative PET imaging agent for the detection of CAIX–expressing tumors. The specific aim of this first-in-human study (NCT06389682) was to assess logistical feasibility, estimate radiochemical safety, and calculate radiation absorbed doses per unit of radioactivity administered. Methods: This was a single-center, open-label, single-dose study of 68 Ga-NYM005. The sample was composed of nine healthy volunteers. A standard 3+3 dose-escalation design was used to administer a single IV dose of 55, 110 or 220 MBq of 68 Ga-NYM005.Each volunteer underwent whole bodyPET/CT imaging at about 0.5h, 1h, 2h and 3h p.i. Blood and urine were sampled at pre-specified times. Vital signs and 12-lead electrocardiograms were performed within 1h after the last scan. Adverse events were assessed from 2-to-5 days post-injection. Results: All volunteers tolerated the procedures well. There were no subjective complaints and no observable adverse events on serial vital sign measurements, clinical laboratory tests, and electrocardiograms. Image quality was uniformly high, making the identification of individual organs boundaries feasible. In females, the highest mean absorbed doses were found in the kidneys (0.23 mGy/MBq), stomach wall (0.15 mGy/MBq), and pancreas (0.12 mGy/MBq), with a mean whole-body effective dose of 0.04 mSv/MBq. In males, the highest mean absorbed doses were also found in the kidneys (0.17 mGy/MBq), stomach wall (0.16 mGy/MBq), and pancreas (0.11 mGy/MBq), with a mean whole-body effective dose of 0.04 mSv/MBq. Absorbed doses in the liver and red marrow were low in all volunteers. After the administration of 68 Ga-NYM005, the drug concentrations in blood rapidly decreased over time. The systemic exposure (C max and AUC (0-t) ) of 68 Ga-NYM005 in volunteers increased linearly with the dose level from1.5 to 6 mCi. Conclusions: 68 Ga-NYM005 was found to be reasonably well tolerated. There were no subjective or observable effects of the tracer in any of the subjects. No significant changes in vital signs, laboratory values, or electrocardiograms were observed. OLINDA dosimetry estimates indicated the absorbed doses in normal organs were unremarkable and typical of other Gallium-68 radiotracers. Radiokinetic analysis showed that 68 Ga-NYM005 was rapidly cleared from the blood, which will likely make it feasible to acquire the scans within one hour of tracer administration. The quality of the PET/CT scan images seems very high, suggesting that 68 Ga-NYM005 could be a very patient-friendly and clinically effective tracer for staging and then the longitudinal surveillance of patients with clear cell renal cell carcinoma. Clinical trial information: NCT06389682 .