Comparison of intratumoral distribution of 99mTc-MIBI and deoxyglucose in mouse breast cancer models.

Abstract

The aims of this study were to evaluate the distribution of 99mTc-methoxyisobutylisonitrile (MIBI) in 3 animal models of breast cancer, the effect of radiotherapy on 99mTc-MIBI uptake, and the relationship between uptake and microvessel density. We used syngeneic, subcutaneously transplanted FM3A, MM48, and Ehrlich mouse breast cancer. 99mTc-MIBI and FDG were injected intravenously, and tumor uptake was measured 30 min later. Double-tracer macroautoradiography (ARG) images were prepared with 99mTc-MIBI and 2-deoxy-D-[1-14C]-glucose (14C-DG), analyzed quantitatively, and compared with histology. The radiotherapeutic effects of 20 Gy x-ray irradiation were monitored by measuring tumor volume, tumor uptake, and ARG findings using 99mTc-MIBI and FDG in FM3A tumors. Microvessel density was quantified by immunohistochemical staining for CD34 and compared with ARG using 99mTc-MIBI in FM3A tumors. FM3A, MM48, and Ehrlich tumors showed different growth rates and radiosensitivities. Uptake of FDG, but not of 99mTc-MIBI, correlated significantly with growth rates. Compared with 14C-DG, 99mTc-MIBI accumulated more in cancer cells and less in infiltrating fibroblasts and macrophages in all tumor models. Irradiation significantly decreased 99mTc-MIBI uptake, but a rapid increase was noted at recurrence on day 7. Changes in FDG uptake were not significant at recurrence. Microvessel density in tumor tissue correlated significantly with 99mTc-MIBI uptake on ARG. Accumulation of 99mTC-MIBI in cancer cells is preferential and can be used as a sensitive marker to examine the response to radiotherapy. Angiogenesis seems to enhance accumulation of 99mTc-MIBI in tumors. These characteristics may be favorable for tumor imaging using 99mTC-MIBI.