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

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. Methods: 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. Results: 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. Conclusion: 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.