A phase Ia study to estimate the radiochemical and radiation safety of of ⁶⁸ Ga-NYM032, a PSMA-targeted radioligand.

Abstract

e17039 Background: 68 Ga-NYM032 is a radiolabeled small-molecule targeting prostate-specific membrane antigen (PSMA), designed as an imaging agent for detecting PSMA-expressing tumors. The specific aim of this first-in-human study (NCT 06389695) aims to assess logistical feasibility, estimate radiochemical safety, and calculate radiation absorbed doses per unit of radioactivity administered. Methods: This single-center, open-label, single-dose escalation study followed a standard 3+3 design, enrolling nine healthy volunteers across three cohort. Participants received a single dose of 74, 148 or 259 MBq of 68 Ga-NYM032.Post-injection, each volunteer underwent PET/CT imaging at 0.5h, 1h, 2h and 3h p.i. Blood and urine samples were collected at predefined intervals. Vital signs and 12-lead electrocardiogram were performed within 1h post-imaging. Adverse events were monitored over 2 to 5 days following 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. After the administration of 68 Ga-NYM032, OLINDA dosimetry calculations revealed the highest absorbed doses in the kidneys (0.25 mGy/MBq) and urinary bladder wall (0.13 mGy/MBq), with a mean effective dose of 0.02 mSv/MBq, corresponding to 1.5–5.2 mSv for injected doses of 74–259 MBq. Lower absorbed doses were observed in the liver and red marrow. Pharmacokinetic analysis indicated a rapid decline in blood drug concentration, with systemic exposure (C max and AUC (0-t) ) increasing with dose escalation. Conclusions: This Phase Ia study confirms that 68 Ga-NYM032 is well tolerated in healthy volunteers, with no significant safety concerns observed. The dosimetry results indicate that the absorbed doses in normal organs remain within safe limits. Pharmacokinetic data show rapid clearance from the bloodstream, and the quality of the PET/CT scan images seems very high. Clinical trial information: NCT06389695 .