**5.1 Small molecules**

Several radiolabeled small molecules have been applied for the detection and therapy of breast and prostate tumors and leukemia (Cornelissen & Vallis, 2010). For example, radiolabeled estrogens and estrogen receptor antagonists are bound to the estrogen receptor, a nuclear membrane receptor, which then translocate to the nucleus. 123I- tamoxifen, an estrogen receptor (ER) antagonist, has been used as a diagnostic tool to determine estrogen receptor status in patients with breast or head-and-neck cancer (Wiele et al., 2001). Other

Breast Cancer: Radioimmunoscintigraphy and Radioimmunotherapy 173

can tolerate harsh chemical conditions and are easy to be purified and modified. The common peptides that are used in molecular imaging and therapy of breast cancer are somatostatin, bombesin, neuropeptide Y (NPY) and vasoactive intestinal peptide (VIP) (Ferro-Flores et al., 2010). The important disadvantage of peptides is rapid degrading from

Antibodies are now increasingly recognized as important biological agents for the detection and treatment of cancer (Sharkey & Goldenberg, 2006). In the 1970s, polyclonal antibodies were already essential components of medical diagnosis as well as for therapy as antitoxins for the prevention of tetanus and other diseases (Goldsmith & Signore, 2010). The development of monoclonal antibody technology by Kohler and Milstein in the 1970s accelerated the exploitation of the chemo-specificity of antibodies for diagnostic and therapeutic purposes (Goldsmith & Signore, 2010). In the last two decades several different monoclonal antibodies have been approved by the Food and Drug Administration (FDA) for therapeutic purposes and some of these have also been radiolabeled for diagnostic and therapeutic purposes (Xiao et al., 2008). For imaging, it is highly desirable that targeting agents are rapidly excreted from the body. It is also essential that the targeting agent binds rapidly to its target, reducing the time between injection and imaging. The application of monoclonal antibodies for therapy and diagnosis is limited by generation of an immune response known as human anti-mouse antibody (HAMA) response (Salouti et al., 2011). One of the most successful approaches to overcome immunogenicity is "humanization" of rodent mAbs by genetic engineering (Waldmann&Morris, 2008). A simple approach to make an antibody to be more humanized is the replacement of the constant domains of the antibody with constant domains of a human antibody. The resulting chimeric antibody contains only the variable regions of murine origin and would therefore be expected to be less immunogenic in people. Many chimeric antibodies have been prepared and shown to retain the full antigen binding ability of the parent murine antibody as well as taking on the constant region effecter functions of the human antibody used (Waldmann&Morris, 2008)**.** Humanization of rodent antibodies can be taken further to produce fully humanized antibodies in the form of reshaped, engineered human antibodies, in which much of the variable domain sequences are also replaced by human antibody sequence. In these approaches, the antigen binding loops are derived from the rodent antibody and much of the supporting framework is humanized (Waldmann&Morris, 2008)**.** Targeting agents that have been approved for breast cancer include trastuzumab and pertuzumab directed against human epidermal growth factor receptor 2 (HER2) and bevacizumab, directed against vascular endothelial growth factor (VEGF) (Goldsmith & Signore, 2010). Several other targeting agents are currently under evaluation in preclinical and clinical trials (Carl &

The use of mAbs has presented challenges in radionuclide imaging. Because of their large size (molecular weight of ~150 kDa), mAbs penetrate slowly and have long residence time in the blood circulation (days-weeks) due to active recycling by the neonatal Fc receptor, leading to limited tumor-to-normal organs ratio in biodistribution and low contrast images for the detection of biomarkers/tumors (Jonathan et al., 2000). Advances in protein

blood by endogenous peptidases and proteases (Ferro-Flores et al., 2010).

**5.5 Antibodies** 

Roland, 2001).

**5.5.1 Antibody derivatives** 

small-molecule radiopharmaceuticals include 125I-daunorubicin, 111In-folate, 123/131I metaiodo- benzyl-guanidine (MIBG), 125I-iododeoxyuridine and 111In-bleomycin (Jalilian et al., 2006, 2007)**.** Small molecules such as tyrosine kinase inhibitors (TKIs) are less specific than therapeutic monoclonal antibodies (mAbs) (Huang & Armstrong,2004) and some of them can inhibit multiple targets simultaneously including cell receptors or signal transduction pathway proteins leading to a higher risk for toxicity (Xia et al., 2005).
