医学
正电子发射断层摄影术
分子成像
癌症
抗体
克洛丹
荧光寿命成像显微镜
病理
癌症研究
核医学
荧光
体内
免疫学
化学
内科学
紧密连接
生物
物理
量子力学
生物技术
生物化学
作者
Chuanke Zhao,Zhuona Rong,Jin Ding,Lixin Wang,Bing Wang,Lei Ding,Meng Lin,Xiangxi Meng,Feng Wang,Zhi Yang,Chengchao Shou,Hua Zhu
标识
DOI:10.1021/acs.molpharmaceut.1c00947
摘要
Claudin 18.2 (CLDN18.2) is a new potential target for cancer therapy, especially for advanced gastric cancer (AGC). A molecular targeting probe is of importance for patient stratification and therapeutic guidance. Here, we explored an antibody-dependent molecular imaging strategy for specific detection and surgery guidance based on a CLDN18.2-specific antibody, 5C9. Two imaging probes, 124I-5C9 and Cy5.5-5C9, were synthesized. The specificity to CLDN18.2 being evidenced in the cellular experiments with control, the diagnostic utility was assessed by immunopositron emission tomography (immuno-PET) and fluorescence imaging using xenograft models. A near-infrared fluorescent II imaging probe FD1080-5C9 was designed to facilitate the comprehensive surgical removal of lesions. 124I-5C9 immuno-PET imaging clearly delineated subcutaneous CLDN18.2-positive tumors, with a peak uptake (maximum standardized uptake value; SUVmax) of 2.25 ± 0.30, whereas the highest values for the 124I-IgG and blocking groups were 0.70 ± 0.13 and 0.66 ± 0.12, respectively. Cy5.5-5C9 fluorescence imaging showed similar results. As proof of the diagnosis and guided surgery (DGS) concept, 124I-5C9 and FD1080-5C9 were simultaneously administered in orthotopic CLDN18.2-positive tumor models, facilitating the comprehensive resection of tumor tissue. Combined, 124I-5C9 and FD1080-5C9 are both promising DGS tools: the former reveals CLDN18.2 in lesions as a PET probe, and the latter can guide surgery. These results provide a utility molecular imaging strategy for specific detection and surgery guidance based on a CLDN18.2-specific antibody both in AGC and other cancers.
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