68Ga-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

doi:10.2967/jnumed.123.267110

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

J Nucl Med. 2024 Apr 11:jnumed.123.267110. doi: 10.2967/jnumed.123.267110. Online ahead of print.

Authors

Changsong Qi¹, Rui Guo², Yan Chen², Chenzhen Li³, Chang Liu¹, Miao Zhang¹, Cheng Zhang¹, Xiaotian Zhang¹, Xingguo Hou², Bo Chen⁴, Bing Jia³, Zhi Yang², Lin Shen⁵, Hua Zhu⁶

Affiliations

¹ Department of Early Drug Development, State Key Laboratory of Holistic Integrative Management of Gastrointestinal Cancers, Beijing Key Laboratory of Carcinogenesis and Translational Research, Peking University Cancer Hospital and Institute, Beijing, China.
² Department of Nuclear Medicine, NMPA Key Laboratory for Research and Evaluation of Radiopharmaceuticals (National Medical Products Administration), State Key Laboratory of Holistic Integrative Management of Gastrointestinal Cancers, Beijing Key Laboratory of Carcinogenesis and Translational Research, Peking University Cancer Hospital and Institute, Beijing, China.
³ Medical Isotopes Research Center, Department of Radiation Medicine, School of Basic Medical Sciences, Peking University, Beijing, China; and.
⁴ Chengdu AlpVHHs Co. Ltd., Chengdou, China.
⁵ Department of Early Drug Development, State Key Laboratory of Holistic Integrative Management of Gastrointestinal Cancers, Beijing Key Laboratory of Carcinogenesis and Translational Research, Peking University Cancer Hospital and Institute, Beijing, China; zhuhuabch@pku.edu.cn shenlin@bjmu.edu.cn.
⁶ Department of Nuclear Medicine, NMPA Key Laboratory for Research and Evaluation of Radiopharmaceuticals (National Medical Products Administration), State Key Laboratory of Holistic Integrative Management of Gastrointestinal Cancers, Beijing Key Laboratory of Carcinogenesis and Translational Research, Peking University Cancer Hospital and Institute, Beijing, China; zhuhuabch@pku.edu.cn shenlin@bjmu.edu.cn.

PMID: 38604764
DOI: 10.2967/jnumed.123.267110

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. 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.

Keywords: 68Ga-NC-BCH; CLDN18.2; PET; gastrointestinal cancers.