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

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

  • Anal Chem. 2022 Mar 8;94(9):3819-3830. doi: 10.1021/acs.analchem.1c04701.
Dai Shi 1 2 3 4,  Zhan Si 1 2 3 4,  Zhan Xu 1 2 3 4,  Yuan Cheng 1 2 3 4,  Qingyu Lin 1 2 3 4,  Zhequan Fu 1 2 3 4,  Wenhui Fu 1 2 3 4,  Tingting Yang 1 2 3 4,  Hongcheng Shi 1 2 3 4,  Dengfeng Cheng 1 2 3 4
Affiliations

Affiliations

  • 1 Department of Nuclear Medicine, Zhongshan Hospital, Fudan University, Shanghai 200032, China.
  • 2 Shanghai Institute of Medical Imaging, Shanghai 200032, China.
  • 3 Institute of Nuclear Medicine, Fudan University, Shanghai 200032, China.
  • 4 Cancer Prevention and Treatment Center, Zhongshan Hospital, Fudan University, Shanghai 200032, China.
PMID: 35195007 DOI: 10.1021/acs.analchem.1c04701
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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