Microautoradiographic Study for the Differentiation of Intratumoral Macrophages, Granulation Tissues and Cancer Cells by the Dynamics of Fluorine-18-Fluorodeoxyglucose Uptake

A substantial amount of macrophage infiltration occurs in both human and animal tumors. We previously showed that 2-deoxy-2-[18F]fluoro-D-glucose ([18F]FDG) uptake was higher in tumor-associated macrophages and young granulation tissues than in tumor cells. Differentiation of intratumoral non-neoplastic cells from neoplastic cells is important not only for the reduction of false-positives in FDG-PET tumor studies but also for patient management. A time-course study was performed using micro- and macro-autoradiography and tissue distribution in C3H/He mice bearing transplanted syngeneic FM3A mammary carcinoma and MH134 hepatoma was evaluated to analyze the intratumoral cellular dynamics of [18F]FDG and 2-deoxy-D-[3H]glucose in vivo. The volume-doubling time in vivo was 1.3 days for MH134 and 4.9 days for FM3A, and the survival time of the host was 32.1 and 40.3 days, respectively. The peak uptake of both tracers in the tumor was 60 min after intravenous injection. The uptake by MH134 was 1.7-2.1 times higher than that by FM3A. The intracellular concentration as determined by counting the silver grains on micro-autoradiographic sections showed that the uptake by macrophages and focal small necrotic areas in both tumors was faster than the blood clearance until 15 min after tracer injection. Thus, non-neoplastic cellular elements can be differentiated from viable neoplastic cells by means of the dynamic analysis of [18F]FDG uptake.