99mTc-MIBI in the evaluation of breast cancer biology

Scintigraphic in vivo evaluation of complex cellular processes such as proliferation, apoptosis, receptor/ligand interactions, transport of substrates and metabolism of nutrients in human cancers is a wide and continuing evolving area of investigation in nuclear medicine (Denoyer, et al. 2006; Been et al. 2004; Corsten et al. 2006; Weissleder 2006). A major purpose in this area is the non-invasive detection of well-known biochemical, molecular and histological markers of tumor aggressiveness, invasiveness and resistance to therapy, which may provide rational criteria for a fine tuning of therapeutic strategies in individual patients. In the last decade, 99mTc-labeled lipophilic cations, originally developed as myocardial perfusion agents and subsequently used as tumor-seeking agents in a variety of human neoplasms, emerged as suitable tools to explore specific cellular processes and functions in malignant tumors. Because of the extensive literature on the use of 99mTc-MIBI for the biological characterization of breast lesions, the present chapter will primarily focus on the ability of this compound to trace specific cellular processes in breast cancer. However, the principles outlined for 99mTc-MIBI can be equally applicable to other agents of the same class of compounds. Clinical studies performed to correlate 99mTc-MIBI uptake or clearance with histological, molecular and biochemical markers of several cellular processes including apoptosis, proliferation, P-glycoprotein expression and neoangiogenesis will be reviewed and discussed.