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Development of a CLDN18.2-targeting Immuno-PET Probe for Non-invasive Imaging in Gastrointestinal Tumors

01 Mar, 2023

Authors: 

Yan Chena ,b,1, Xingguo Houb,1, Dapeng Lia,b,1, Jin Dingb, Jiayue Liub, Zilei Wangb, c, Fei Tengd, Hongjun Lid, Fan Zhangd, Yi Gud, Steven Yud, Xueming Qiand, ***, Zhi Yanga,b,e, **, Hua Zhua,b,e,*

aGuizhou University Medicine College, Guiyang, Guizhou Province, 550025, People’s Republic of China

bKey Laboratory of Carcinogenesis and Translational Research (Ministry of Education/Beijing), NMPA Key Laboratory for Research and Evaluation of Radiopharmaceuticals (National Medical Products Administration), Department of Nuclear Medicine, Peking University Cancer Hospital & Institute, Beijing 100142, China

cDepartment of Biochemistry and Molecular Biology, School of Basic Medical Sciences, Southwest Medical University, Luzhou, 646000, China

dSuzhou Transcenta Therapeutics Co., Ltd, Suzhou 215127, China

eInstitute of Biomedical Engineering, Peking University Shenzhen Graduate School, Shenzhen, Guangdong 518055, China

*Corresponding Author. 

**Corresponding Author.

***Corresponding Author.

Background:

According to the cancer epidemiology report released in 2022, lung cancer is the primary cause of cancer death, followed by digestive tract tumors (such as stomach cancer, colorectal cancer, liver cancer, oesophageal cancer, etc.). In China, gastrointestinal cancers account for 45% of cancer-related deaths, likely because gastrointestinal cancers are mostly diagnosed in the advanced stage and patients often have a poor prognosis[[1], [2], [3]]. Gastrointestinal cancers have become the primary medical and economic burden for people in China. In addition to traditional chemotherapy, and immunotherapy, little progress has been made with novel chemotherapies and targeted therapies for gastrointestinal tumors[[4], [5], [6], [7]]. Among the 70 novel first-line agents approved for cancer treatment, only 5 drugs have been approved for advanced gastrointestinal cancer and the survival rates are still low based on data from the last five years[8]. Therefore, strategies to improve the survival of patients with advanced gastrointestinal cancer remain an unmet medical necessity.

Conlusion:

We successfully prepared 89Zr labelling of a GMP grade anti-CLDN18.2 recombinant humanized antibody TST001. [89Zr]Zr-DFO-TST001 exhibited good specificity at the cellular level and rapid tumor accumulation which remained positive from 24 to 96 h. It provides a promising molecular probe for detecting the treatment effects of therapeutic antibodies in humans in real time. It also provides a possibility for the screening and efficacy evaluation of patients targeted for CLDN18.2 therapy in the future.