Applications of 99m TC-Sestamibi in Oncology

Hexakis (2-methoxyisobutylisonitrile) technetium-99m (^99mTc-SestaMIBI) is a radiopharmaceutical used in nuclear medicine for myocardial perfusion imaging. In the literature different non-cardiac applications of ^99mTc-SestaMIBI have been reported. Clinical studies have been performed also in non-oncologic diseases (such as thyroid adenoma, diabetic foot, osteomyelitis, pulmonary actinomycosis, aneurysmal bone cyst, Sudeck's atrophy). Several models for the uptake mechanism of this radiopharmaceutical have been proposed such as binding to an 8-10 kDa cytosolic protein, simple lipid partitioning, or a membrane translocation mechanism involving diffusion and passive transmembrane distribution. Most evidence points in the direction of the third hypothesis. Many studies have indicated that uptake of hexakis (alkylisonitrile) technetium complexes is dependent on mitochondrial and plasma membrane potentials like other lipophilic cations. This explains the initial biodistribution of ^99mTc-SestaMIBI to tissues with negative plasma membrane potentials and with a relatively high mitochondrial content (like heart, liver, kidney and skeletal muscle tissue). Malignant tumours also possess these properties in order to maintain their increased metabolism. This behaviour encouraged the study of ^99mTc-SestaMIBI as an interesting tracer imaging various tumour types: osteosarcoma, brain, lung, breast, nasopharyngeal, parathyroid, and thyroid cancer. Recent research on cell cellular physiology has further revealed an active transport of ^99mTc-SestaMIBI out of the tumour cells, against the potential gradient. The same mechanism is also responsible for resistance to a structurally and functionally different group of cytotoxic agents, such as vinca alkaloids, epipodophyllotoxins, anthracyclins and actinomycin D. This peculiar type of resistance is due to amplification of the mammalian MDR1 gene, located on chromosome 7. For this reason the ^99mTc- SestaMIBI uptake in vivo could permit the prediction of the response to the chemotherapy, when the decreased accumulation of ^99mTc-SestaMlBI implies the presence of P-gp enriched tissues. In the next future a particular attention should be dedicated to this matter since one of the most important goals of the clinical trials is the demonstration of the usefulness of ^99mTc-SestaMIBI for in vivo assessment of multidrug resistance.