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

Xiao-Feng Li, Huijie Jiang, Yuanyuan Ma, Tao Huang, Xindao Yin, A. Cahid Civelek, Baozhong Shen

Department of Diagnostic Radiology, Division of Nuclear medicine, University of Louisville School of Medicine, Louisville, USA.
Department of Diagnostic Radiology, University of Louisville School of Medicine, Louisville, USA.
Department of Radiology, The 4th Hospital of Harbin Medical University, Harbin, China.
Memorial Sloan-Kettering Cancer Center, New York, USA.

DOI: 10.4236/ijmpcero.2013.21004                

Abstract

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 radio- pharmaceuticals such as ¹⁸F-fluoro-2-deoxyglucose (¹⁸F-FDG) ¹⁸F-fluorothymidine (¹⁸F-FLT), ¹⁸F-misonidazole (¹⁸F- FMISO) using the system. We found that ¹⁸F-FLT accumulates in proliferating cancer cells, while ¹⁸F-FMISO and ¹⁸F-FDG mostly accumulate in hypoxic and non-proliferative cancer cells, ¹⁸F-FDG shares roughly similar intratumoral distribution pattern with ¹⁸F-FMISO and IAZGP, but mutually excludes ¹⁸F-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.

Keywords

¹⁸F-Fluoro-2-Deoxyglucose; ¹⁸F-Fluorothymidine; ¹⁸F-Misonidazole; Microenvironment; Hypoxia; Proliferation

Conflicts of Interest

The authors declare no conflicts of interest.

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