**3.5 Immunotherapy**

Immunotherapy (also called biological therapy, biotherapy or biological response modifier therapy) of breast cancer uses patient body's natural ability (immune system) to fight the disease and/or to lesson treatment-related side effects (Diss et al., 1997b). The immunotherapy drugs are bound to specific proteins on breast cancer cells to slow or stop

Breast Cancer: Radioimmunoscintigraphy and Radioimmunotherapy 171

A molecular imaging agent typically consists of a signaling moiety (radionuclide in nuclear medicine) and a functional target. Specific targeting of cancer-associated targets with radiolabeled targeting agents (e.g. antibodies, peptides and non-immunoglobulin proteins) and the use of subsequent visualization systems like gamma camera, SPECT and PET are

Major advances in molecular biology, cellular biology and genomics have substantially improved our understanding of cancers. Now, these advances are being translated into therapy. The term targeted therapy ideally connotes the ability to identify a known therapeutic target that is important in the biology of cancer cells and use a specific agent that can treat the disease by modifying the expression or activity of the target in the growth and progression of the cancer. With this approach, only patients with a likelihood of benefit are treated, so the therapeutic index will hopefully be improved. Selecting a biologically active target is usually the first step in molecular imaging research and leads to the design of a molecular imaging agent. Potential targets include proteins, DNA, RNA, carbohydrates and lipids. Several properties of these biomolecules as imaging targets need to be considered

1. High specificity (i.e. binding specifically to a tumor-associated molecular target with

3. Small size (enabling fast distribution to the tumor and quick clearance from the blood

Molecular probes in nuclear medicine are the proof of principle for targeted molecular imaging and therapy. Molecular nuclear medicine holds the unique potential of being able to find, diagnose and treat diseases as well as to monitor treatment response. Several molecular targeting agents have been approved for clinical uses in nuclear medicine. Many others are under preclinical evaluation with high potential for clinical applications. The molecular targeting agents, that are common in nuclear medicine, are 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

2. High target binding affinity (low subnanomolar binding is typically desired).

5. Staging the extent of disease

**4.2 Targeted molecular therapy** 

and other compartments).

**5.1 Small molecules** 

6. Monitor the clinical course of cancer patients 7. Determine the effectiveness of therapy

8. Early detection of recurrent or metastatic cancer

examples of molecular imaging methods in nuclear medicine.

that are summarized in the following (Meel et al., 2010):

**5. Targeted molecular agents of breast cancer** 

oligonucleotides /PNAs, affibodys, peptides and antibodies.

minimal non-specific binding to non-target molecules).

4. High structural stability for labeling with signaling agents. 5. Available ligands that specifically target these biomolecules.

their growth. Currently, there are at least three FDA-approved antibodies for targeting of breast cancers (Stipsanelli & Valsamaki, 2005; Disis et al., 1994a, 1997b):


Immunotherapy of breast cancer may cause side effects such as fever, chill, pain, weakness, nausea, vomiting, diarrhea, headache, and rash. These side effects generally become less severe after the first treatment. In addition, immunotherapy is a very expensive method for patients.
