Nuclear Medicine Tracers Targeting Tumor-Associated Macrophages

Malignant tumors are the second major disease threatening human health, and their early diagnosis can significantly improve patients’ prognosis. [18F]FDG PET/CT is currently the most important method in nuclear medicine for tumor diagnosis and staging. However, due to variations in the glucose uptake characteristics of tumors, some tumors with low FDG uptake (e.g., gastric mucinous adenocarcinoma and indolent lymphoma) are prone to false-negative results. Therefore, new tumor-specific imaging tracers are urgently needed. Due to the significant differences in target expression among various tumor cells, the method of focusing on a single target is unlikely to work for all tumors. Therefore, researchers are exploring the possibility of targeting tumor-associated macrophages (TAMs) in the tumor microenvironment for imaging because this offers several advantages. First, unlike most tumors, which originate from epithelial cells, TAMs arise from monocyte–macrophage polarization, leading to greater target specificity on their surfaces. Second, TAMs are the most abundant non-tumor cells in the tumor microenvironment, ensuring a certain level of expression abundance. Furthermore, numerous preclinical studies and clinical trials targeting TAMs with immunotherapy are currently underway, making the non-invasive assessment of certain TAM targets’ expression levels a critical issue that needs to be addressed. This article summarizes the potential targets and nuclear medicine tracers for targeting TAMs.