Molecular Imaging of Breast Cancer Tissue via Site-Directed Radiopharmaceuticals

The American Cancer Society reports that ~261,100 new cases of invasive and in situ breast cancer were diagnosed in 2010, and nearly 40,000 fatalities were attributed to this disease (American Cancer Society, 2010). Although death rates have steadily decreased since 1990, breast cancer currently ranks second in cancer deaths among women. Improvements in detection, treatment, and prevention education contribute to slow the incidence rate, and rapidly evolving nuclear medicine techniques have emerged as a formidable opponent to female breast cancer. The involvement of nuclear medicine imaging modalities in both the detection and diagnosis of breast cancer has increased in recent years (Gopalan et al., 2002). In contrast to earlier imaging methods, in which the transmission of various forms of energy through tissue is employed to generate an image, nuclear medicine imaging techniques are based on detection of the energy emitted from radioactive tracers that are injected into the body and subsequently accumulate locally in specific tissues (Nass et al., 2001). The classification of these techniques as either positron emission tomography (PET) or single photon emission computed tomography (SPECT) imaging modalities is determined by the radionuclide that is utilized to synthesize a given radiotracer. The theory behind nuclear medicine imaging techniques to detect and diagnose breast cancer is founded on preferential radiopharmaceutical uptake by cancerous cells as a result of alterations in metabolic rate, vascularity, or receptor expression which are associated with malignancy. Although both PET and SPECT are commonly employed to detect a variety of malignancies, neither imaging technique has achieved clinical acceptance as a method of imaging breast cancer due to the lack of sensitivity and specificity demonstrated by available radiotracers (Gopalan et al., 2002; Nass et al., 2001; Rosen et al., 2008). Presently, there is only one radiopharmaceutical, the SPECT imaging agent technetium-99m methoxy-isobutyl-isonitrile (99mTc-sestamibi, Miraluma®), that has received FDA approval for use as a diagnostic adjunct to mammography (Gopalan et al., 2002; Nass et al., 2001; Rosen et al., 2008). Although the mechanism governing the concentration of 99mTc-sestamibi in cancer cells is not fully understood, it may be related to the degree of cellular proliferation and vascular permeability (Nass et al., 2001). Once inside malignant cells, 99mTc-sestamibi is