124I-Labeled Immuno-PET Targeting hTREM2 for the Diagnosis of Gastric Carcinoma.

ABSTRACT

Low ß-2-[18F]-fluoro-2-deoxy-d-glucose (18F-FDG) uptake in gastric mucinous adenocarcinoma may cause false-negative diagnosis and erroneous staging. Thus, there is an urgent need for developing tumor-specific imaging agents in gastric cancer diagnostics. Triggering receptor expressed on myeloid cells 2 (TREM2) is a transmembrane protein expressed on the surface of tumor-associated macrophages (TAMs) and is considerably overexpressed in tumor tissues. This study aimed to develop new human TREM2 (hTREM2)-targeting imaging agents to diagnose and monitor gastric cancer. We established a cell line, MGC803, with upregulated expression of hTREM2, at the cell surface. We produced a monoclonal antibody (5-mAb) against hTREM2 by immunizing mice with the hTREM2 antigen to obtain the antibody fragment 5-F(ab')2 using an immunoglobulin G-degrading enzyme of Streptococcus pyogenes (IdeS). Another anti-TREM2-mAb (clone 237920) and its fragment anti-TREM2-F(ab')2 were employed for the comparative study in vitro and in vivo. After 124I labeling, we constructed the probes 124I-5-mAb, 124I-5-F(ab')2, 124I-anti-TREM2-mAb, and 124I-anti-TREM2-F(ab')2. We found that 5-mAb exhibited higher hTREM2 affinity and slower blood clearance than anti-TREM2-mAb, whose corresponding F(ab')2 fragments demonstrated the same trend. The micro-PET/CT revealed that 124I-5-F(ab')2 exhibited advantages of tumor enrichment and fast metabolism. The biodistribution study results were consistent with those of micro-PET/CT. Among the four tracers, 124I-5-F(ab')2 was the most suitable specific radiotracer for targeting hTREM2 and displayed potential utility as a tumor-imaging tracer for diagnosing gastric carcinoma.