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. Methods: 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. Results: 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. Conclusion: 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.

⁶⁸ Ga标记纳米抗体（ ⁶⁸ Ga-NC-BCH）是一种基于单域抗体的PET成像剂。我们对用于 PET 的 ⁶⁸ Ga-NC-BCH 进行了首次人体研究，以确定其体内生物分布、代谢、辐射剂量测定、安全性以及定量 Claudin-18 亚型 2 (CLDN18.1) 的潜力。 2)在胃肠道癌症患者中的表达。方法：首先合成了探针 ⁶⁸ Ga-NC-BCH，并对人胃腺癌细胞系和异种移植小鼠模型进行了临床前评价。接下来，我们使用全身 PET/CT 扫描仪对一组晚期胃肠癌患者进行了转化研究。评估了放射性药物的生物分布、放射剂量测定以及肿瘤摄取与 CLDN18.2 表达之间的关系。结果： ⁶⁸ Ga-NC-BCH制备稳定，具有良好的放化性能。根据临床前评估， ⁶⁸ Ga-NC-BCH 表现出快速的血液清除、对 CLDN18.2 的高亲和力以及在 CLDN18.2 阳性细胞和异种移植小鼠模型中的高特异性摄取。 ⁶⁸ Ga-NC-BCH 在胃和肾中表现出高摄取，在胰腺中表现出少量摄取。与 ¹⁸ F-FDG相比， ⁶⁸ Ga-NC-BCH在不同CLDN18.2表达水平的病灶中的摄取表现出显着差异。结论：PET SUV 与 CLDN18.2 表达之间存在明显的相关性，表明 ⁶⁸ Ga-NC-BCH PET 可用作优化肿瘤中针对 CLDN18.2 的治疗的伴随诊断工具。