68 Ga-NODAGA-SNA014 whole-body PET imaging to detect Claudin18.2–positive pancreatic cancer lesions.

3065 Background: 68 Ga-labeled nanobody ( 68 Ga-NODAGA-SNA014) is a PET radiotracer based on a single-domain antibody. We conducted a first-in-human (FIH) evaluation of 68 Ga-NODAGA-SNA014 to characterize in vivo biodistribution, metabolism, radiation dosimetry, and safety, and to explore its ability to noninvasively quantify Claudin-18.2 (CLDN18.2) expression in patients with gastrointestinal cancers. Methods: 68 Ga-NODAGA-SNA014 was synthesized and first assessed preclinically in human pancreatic cancer cell lines and xenograft mouse models to evaluate affinity, specificity, and pharmacokinetics. We then performed a translational pilot study in 15 patients with pancreatic cancer imaged on a total-body (panoramic) PET/CT system. Whole-body biodistribution, organ dosimetry, and the association between lesion uptake and CLDN18.2 expression were analyzed and compared with 18 F-FDG, where available. Results: 68 Ga-NODAGA-SNA014 was produced reliably with favorable radiochemical characteristics. In preclinical studies, the tracer exhibited rapid blood clearance, high affinity for CLDN18.2, and specific uptake in CLDN18.2-positive cells and xenografts. In patients, physiologic uptake was highest in the stomach and kidneys, with mild uptake in the pancreas. Lesion uptake varied by CLDN18.2 expression level, and 68 Ga-NODAGA-SNA014 demonstrated more precise differentiation of CLDN18.2-high versus CLDN18.2-low lesions than 18 F-FDG. Conclusions: PET uptake (SUV) of 68 Ga-NODAGA-SNA014 correlated with CLDN18.2 expression, supporting its potential as a noninvasive companion diagnostic to guide and optimize CLDN18.2-targeted therapies.