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

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.

Immunosuppressive landscape in hepatocellular carcinoma revealed by single-cell sequencing

“…As accumulating evidence has revealed a role of TREM2 in tumor-associated macrophages (TAMs) and myeloid-derived suppressor cells (MDSCs), we analyzed the expression of TREM2 in the eight clusters and found it to be high in cluster 1, cluster 2 and cluster 4 (Figure 3E), which were all derived from cancer tissues. TREM2 has been linked to poor prognosis and is a vital in inducing immunosuppression in the TME (32)(33)(34)(35)(36). To further study the clinical value of TREM2, we divided 360 HCC patients from the TCGA LIHC cohort into two groups according to the expression level of TREM2.…”

Targeting Tumor-Associated Macrophages for Imaging

“…TAMs had a higher expression level of triggering receptors expressed on myeloid cells (TREMs) than M1 macrophages. Shi et al [ 50 ] established a novel radioligand, 68 Ga-NOTA-COG1410, for TREM2-targeted PET imaging. By building a macrophage/tumor cell coculture system to obtain tumor-associated macrophages (TAMs), researchers verified the tumor targeting and excellent imaging ability of this nanoprobe.…”

Exploration of 68Ga-DOTA-MAL as a Versatile Vehicle for Facile Labeling of a Variety of Thiol-Containing Bioactive Molecules

“…The development of effective bifunctional chelators has broadened the application prospects of metal nuclides in nuclear medicine. Numerous literature studies have described the process of radiolabeling biomolecules using bifunctional chelators, which are first conjugated to biomolecules via primary amino groups and then followed by radiolabeling. , However, this approach cannot satisfy all situations effectively. (1) When the labeled substrates that are not commercialized or need to be extracted from patients, the conjugation of the active ester and primary amine is usually carried out under weak alkaline conditions, while the radiolabeling of 68 Ga often occurs in an acidic environment, the replacement of the buffer system is inevitable.…”