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

⁶⁸ Ga-labeled nanobody ( ⁶⁸ Ga-NC-BCH) is a single-domain antibody-based PET imaging agent. We conducted a first-in-humans study of ⁶⁸ Ga-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. Methods: Initially, we synthesized the probe ⁶⁸ Ga-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. Results: ⁶⁸ Ga-NC-BCH was stably prepared and demonstrated good radiochemical properties. According to preclinical evaluation, ⁶⁸ Ga-NC-BCH exhibited rapid blood clearance, high affinity for CLDN18.2, and high specific uptake in CLDN18.2-positive cells and xenograft mouse models. ⁶⁸ Ga-NC-BCH displayed high uptake in the stomach and kidney and slight uptake in the pancreas. Compared with ¹⁸ F-FDG, ⁶⁸ Ga-NC-BCH showed significant differences in uptake in lesions with different levels of CLDN18.2 expression. Conclusion: A clear correlation was detected between PET SUV and CLDN18.2 expression, suggesting that ⁶⁸ Ga-NC-BCH PET could be used as a companion diagnostic tool for optimizing treatments that target CLDN18.2 in tumors.
(© 2024 by the Society of Nuclear Medicine and Molecular Imaging.)