TREM1-PET imaging maps whole-body innate immune responses in a mouse model of metastatic melanoma

Abstract

Abstract Poor treatment response in brain metastases is largely attributed to anti-tumor T-cell suppression through the modulation of tumor-associated myeloid cells (TAMCs), resulting in immune evasion. Triggering receptor expressed on myeloid cells-1 (TREM1) is a membrane receptor highly expressed on TAMCs that is associated with poor clinical outcomes and of interest as a potential imaging biomarker of myeloid cell function, prognosis, and treatment response. Here we evaluate TREM1-targeted positron emission tomography (PET) tracer, [ 64 Cu]TREM1-mAb, for TAMC detection in a murine model of intracranial metastatic melanoma. Forty-eight hours after tracer administration, PET imaging revealed significantly higher [ 64 Cu]TREM1-mAb signal in implanted tumors compared to contralateral brain parenchyma or sham brains. Ex vivo gamma counting and autoradiography confirmed significantly elevated, tumor-localized signal, while markedly lower uptake with [ 64 Cu]-isotype control-mAb confirmed tracer specificity. Similar patterns were seen in the lymphoid organs, including bone marrow and spleen. Flow cytometry confirmed TREM1 expression in myeloid cells alone in brain and spleen. We conclude that [ 64 Cu]TREM1-mAb is a promising PET tracer for the detection of increased TREM1 + myeloid cells in the tumor microenvironment and peripheral tissues.