<sup>68</sup>Ga-NC-BCH Whole-Body PET Imaging Rapidly Targets Claudin18.2 in Lesions in Gastrointestinal Cancer Patients
Changsong Qi, Rui Guo, Yan Chen, Chenzhen Li, Chang Liu, Miao Zhang, Cheng Zhang, Xiaotian Zhang, Xingguo Hou, Bo Chen, Bing Jia, Zhi Yang, Lin Shen, Hua Zhu
Abstract
<sup>68</sup>Ga-labeled nanobody (<sup>68</sup>Ga-NC-BCH) is a single-domain antibody–based PET imaging agent. We conducted a first-in-humans study of <sup>68</sup>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. <b>Methods:</b> Initially, we synthesized the probe <sup>68</sup>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. <b>Results:</b><sup>68</sup>Ga-NC-BCH was stably prepared and demonstrated good radiochemical properties. According to preclinical evaluation,<sup>68</sup>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. <sup>68</sup>Ga-NC-BCH displayed high uptake in the stomach and kidney and slight uptake in the pancreas. Compared with <sup>18</sup>F-FDG, <sup>68</sup>Ga-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 <sup>68</sup>Ga-NC-BCH PET could be used as a companion diagnostic tool for optimizing treatments that target CLDN18.2 in tumors.