99mTc-MIBI in the evaluation of breast cancer biology

A major area of interest in nuclear medicine is the scintigraphic in vivo evaluation of complex cellular processes involved in tumour growth, progression and response to treatment with the aim of defining the bio- logical properties that may orient clinicians towards different adjustments of therapy in individual patients. In the last decade, 99mTc-labelled lipophilic cations emerged as suitable tools to trace specific cellular processes and functions in a variety of malignant tumours, including breast cancer. Among these agents, 99mTc-methoxyiso- butylisonitrile (MIBI) is the most widely evaluated tracer and may serve as a paradigm for this class of compounds. Many clinical studies have been performed to correlate 99mTc-MIBI uptake or clearance with histological, molecular and biochemical markers of various cellular processes, including apoptosis, proliferation, P-glyco- protein expression and neoangiogenesis. The final pic- ture emerging from these studies is that the early tracer uptake reflects the mitochondrial status, which is affected by both apoptosis and proliferation, whereas the tracer clearance reflects the activity of drug transporters such as P-glycoprotein. On the basis of the imaging parameter chosen for the analysis of 99mTc-MIBI scan in breast cancer patients, the biological information provided may be related to different cellular processes that ultimately govern tumour response to treatment.