Synthesis and Evaluation of 68Ga-NOTA-COG1410 Targeting to TREM2 of TAMs as a Specific PET Probe for Digestive Tumor Diagnosis

IF 6.7 1区化学 Q1 CHEMISTRY, ANALYTICAL

Analytical Chemistry Pub Date : 2022-02-23 DOI:10.1021/acs.analchem.1c04701

Dai Shi, Zhan Si, Zhan Xu, Yuan Cheng, Qingyu Lin, Zhequan Fu, Wenhui Fu, Tingting Yang, Hongcheng Shi*, Dengfeng Cheng*

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引用次数: 8

Abstract

Currently, positron emission tomography/computed tomography (PET/CT) is an important method for the discovery and diagnosis of digestive system tumors. However, the shortage of specific imaging tracer limits the effectiveness of PET. Triggering receptor expressed on myeloid cells 2 (TREM2) as an M2-type macrophage biomarker is receiving much attention considering its high abundance and specificity, which could be an ideal target for PET imaging. First, the expression of TREM2 in tumors and corresponding normal tissues was analyzed using a database and was verified by tissue microarrays and murine model slices, and we found that the expression of TREM2 in tumor tissues was significantly higher than that in normal tissues and enteritis tissues. Then, we established a macrophage co-culture system to obtain tumor-associated macrophages (TAMs). Compared with M1-type macrophages and tumor cells, TAMs had a higher expression level of TREM2. The novel radioligand ⁶⁸Ga-NOTA-COG1410 was successfully synthesized for TREM2 targeting PET imaging. The biodistribution and micro-PET/CT results showed high uptake of ⁶⁸Ga-NOTA-COG1410 in the tumor but not in areas of inflammation. The data testified that ⁶⁸Ga-NOTA-COG1410 was a specific radioligand targeting TREM2, which could be used to distinguish tumors from inflammation. Using ⁶⁸Ga-NOTA-COG1410, the effectiveness of PET on digestive tumors imaging may be enhanced.

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靶向TAMs TREM2的68Ga-NOTA-COG1410作为消化道肿瘤特异性PET探针的合成与评价

目前，正电子发射断层扫描/计算机断层扫描(PET/CT)是发现和诊断消化系统肿瘤的重要方法。然而，特异性显像示踪剂的缺乏限制了PET的有效性。髓样细胞触发受体2 (TREM2)作为一种m2型巨噬细胞生物标志物，因其高丰度和特异性而备受关注，可能成为PET成像的理想靶点。首先，利用数据库分析TREM2在肿瘤和相应的正常组织中的表达，并通过组织芯片和小鼠模型切片进行验证，我们发现TREM2在肿瘤组织中的表达明显高于正常组织和肠炎组织。然后，我们建立了巨噬细胞共培养系统，获得肿瘤相关巨噬细胞(tam)。与m1型巨噬细胞和肿瘤细胞相比，tam具有更高的TREM2表达水平。成功合成了用于TREM2靶向PET成像的新型放射性配体68Ga-NOTA-COG1410。生物分布和微pet /CT结果显示，68Ga-NOTA-COG1410在肿瘤中有较高的吸收，而在炎症区域没有。数据证实，68Ga-NOTA-COG1410是靶向TREM2的特异性放射配体，可用于区分肿瘤和炎症。使用68Ga-NOTA-COG1410，可以提高PET对消化道肿瘤成像的有效性。

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来源期刊

Analytical Chemistry 化学-分析化学

CiteScore

12.10

自引率

12.20%

发文量

1949

审稿时长

1.4 months

期刊介绍： Analytical Chemistry, a peer-reviewed research journal, focuses on disseminating new and original knowledge across all branches of analytical chemistry. Fundamental articles may explore general principles of chemical measurement science and need not directly address existing or potential analytical methodology. They can be entirely theoretical or report experimental results. Contributions may cover various phases of analytical operations, including sampling, bioanalysis, electrochemistry, mass spectrometry, microscale and nanoscale systems, environmental analysis, separations, spectroscopy, chemical reactions and selectivity, instrumentation, imaging, surface analysis, and data processing. Papers discussing known analytical methods should present a significant, original application of the method, a notable improvement, or results on an important analyte.