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

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 Ga-68-NOTA-COG1410 was successfully synthesized for TREM2 targeting PET imaging. The biodistribution and micro-PET/CT results showed high uptake of Ga-68-NOTA-COG1410 in the tumor but not in areas of inflammation. The data testified that Ga-68-NOTA-COG1410 was a specific radioligand targeting TREM2, which could be used to distinguish tumors from inflammation. Using Ga-68-NOTA-COG1410, the effectiveness of PET on digestive tumors imaging may be enhanced.