ABSTRACT The translocator protein (TSPO) is a mitochondrial biomarker overexpressed in activated immune cells and various tumors that is an attractive target for positron emission tomography (PET) imaging of inflammation and the tumor microenvironment. We designed and evaluated the novel TSPO‐targeted PET tracer, 64 Cu‐purine ( 64 Cu 5 ), constructed from a purine scaffold conjugated to a NOTA chelator. Molecular docking analysis indicated that the DOTA analog exhibited slightly higher TSPO binding affinity than did the NOTA derivative; however, the NOTA chelator was selected for 64 Cu labeling due to its superior radiochemical yield and stability. 64 Cu 5 demonstrated high radiochemical purity, excellent in vitro and in vivo stability, and moderate lipophilicity, which minimized nonspecific uptake. In vitro, 64 Cu 5 showed significantly higher uptake in inflammatory macrophages than in tumor cells. In vivo PET imaging and biodistribution studies revealed preferential accumulation in inflamed and tumor tissues, with reduced uptake following PK11195 administration. Autoradiography and immunohistochemistry confirmed tracer accumulation in both inflamed and tumor tissues, reflecting the presence of inflammation within the tumor microenvironment. Overall, these findings suggest that 64 Cu 5 is a promising TSPO‐targeting PET radiotracer for imaging inflammation‐associated processes in tumors.
Ochirsukh et al. (Mon,) studied this question.
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