⁶⁸Ga-NC-BCH Whole-Body PET Imaging Rapidly Targets Claudin18.2 in Lesions in Gastrointestinal Cancer Patients.

Abstract

⁶⁸Ga-labeled nanobody (⁶⁸Ga-NC-BCH) is a single-domain antibody-based PET imaging agent. We conducted a first-in-humans study of ⁶⁸Ga-NC-BCH for PET to determine its in vivo biodistribution, metabolism, radiation dosimetry, safety, and potential for quantifying claudin-18 isoform 2 (CLDN18.2) expression in gastrointestinal cancer patients. <b>Methods:</b> Initially, we synthesized the probe ⁶⁸Ga-NC-BCH and performed preclinical evaluations on human gastric adenocarcinoma cell lines and xenograft mouse models. Next, we performed a translational study with a pilot cohort of patients with advanced gastrointestinal cancer on a total-body PET/CT scanner. Radiopharmaceutical biodistribution, radiation dosimetry, and the relationship between tumor uptake and CLDN18.2 expression were evaluated. <b>Results:</b> ⁶⁸Ga-NC-BCH was stably prepared and demonstrated good radiochemical properties. According to preclinical evaluation,⁶⁸Ga-NC-BCH exhibited rapid blood clearance, high affinity for CLDN18.2, and high specific uptake in CLDN18.2-positive cells and xenograft mouse models. ⁶⁸Ga-NC-BCH displayed high uptake in the stomach and kidney and slight uptake in the pancreas. Compared with ¹⁸F-FDG, ⁶⁸Ga-NC-BCH showed significant differences in uptake in lesions with different levels of CLDN18.2 expression. <b>Conclusion:</b> A clear correlation was detected between PET SUV and CLDN18.2 expression, suggesting that ⁶⁸Ga-NC-BCH PET could be used as a companion diagnostic tool for optimizing treatments that target CLDN18.2 in tumors.