A Model System for Validation of PET Radiopharmaceuticals: Focusing on Tumor Microenvironment

Positron emission tomography (PET) imaging has emerged as an important clinical tool for cancer management, and specifically targeted radiopharmaceuticals play critical roles on PET molecular imaging. Solid cancers have highly complex and heterogeneous microenvironment, this review focused on those microenvironmental factors such as hypoxia, proliferation and perfusion and, accordingly, a novel test system for validation of current and novel targeted imaging radiopharmaceuticals. In this review, we have introduced the establishment of cancer and metastases models in nude mice, visualization of microenvironmental components of hypoxia, proliferation, perfusion, stroma and necrosis in cancers and metastases for establishing the microenvironment based model system, and validation of several radiopharmaceuticals such as F-fluoro-2-deoxyglucose (F-FDG) F-fluorothymidine (F-FLT), F-misonidazole (FFMISO) using the system. We found that F-FLT accumulates in proliferating cancer cells, while F-FMISO and F-FDG mostly accumulate in hypoxic and non-proliferative cancer cells, F-FDG shares roughly similar intratumoral distribution pattern with F-FMISO and IAZGP, but mutually excludes F-FLT. This model system validated current tracers for imaging glucose metabolism, hypoxia and proliferation in cancer and metastases, therefore, can be used for novel targeted radiopharmaceuticals validation.