**2.4 Diffuse Optical Tomography (DOT)**

166 12 Chapters on Nuclear Medicine

modalities and describes application of nuclear medicine techniques and targeted molecular

Mammography is a gold standard imaging method for breast cancer screening, detection and diagnosis in women under forty with a relatively high sensitivity in the range of 85-90% (Berg et al., 2004). This method is a national screening program in the United Kingdom (Glasspool & Evans., 2000). Although mammography is an effective imaging tool, it is not without limitations like many other diagnostic modalities. First, the sensitivity of mammography decreases dramatically in young patients due to their dense breast tissues. On the other hand, its ability to detect malignant lesions in young female patients decreases to 68% (Nystrom et al., 2002, Kopans, 1992). As a result, some patients with breast cancer are missed and some others without a malignant tumor undergo unnecessary biopsies due to incorrect mammography findings. Secondly, mammography in patients evaluated following breast surgery or radiotherapy, is unreliable with a false negative rate of 25-45%, because it cannot always differentiate benign from malignant diseases (Fass, 2008). Many efforts have ever been taken to establish new tests to enable us to collect more complete information by non-invasive methods. These efforts minimize the use of breast biopsy in women who do not have breast cancer. Therefore, many other imaging modalities such as ultrasonography (US), magnetic resonance imaging (MRI), diffuse optical tomography (DOT), computed tomography (CT) and measurement of tumor markers in blood serum have been initiated to

Ultrasonography is an important adjunct to mammography for both diagnosis and characterization of breast cancer and is routinely used in this role (Fass, 2009). It is noninvasive, easily available, relatively cheap and also recommended for pregnant or lactating women when ionizing radiation may not be recommended (Schueller et al., 2008). It has been found that ultrasonography, when combined with mammography, can prevent up to 22% of unnecessary biopsies (Zonderland, 2000). Although ultrasonography can reliably differentiate a cystic lesion from a solid lesion, it does not provide a high specificity to distinguish benign from malignant lesions (Balleyguier et al., 2008; Sauer et al., 2005). Another disadvantage of this method as a screening tool, when applied to general population, is low sensitivity and specificity and furthermore it is operator-dependent

Breast cancer was one of the first that was examined using MRI (Ross et al., 1982). This method is very useful for further evaluation when mammography and ultrasonography are indeterminate to study the presence or location of a suspect abnormality (Glasspool et al., 2000). However, due to cost reasons, low access and high false positives, MRI is not yet considered as a screening exam for breast cancer except for special cases. MRI of breast cancer is recommended in the repeated screening of patients who have the increased risk of radiation induced DNA mutations (Fass, 2008). MRI is used to screen women with a family history of breast cancer, women with very dense breast tissues or women with silicone

implants that can obscure pathology in mammography (Fass, 2008).

imaging in the investigation of patients with breast cancer.

increase the diagnostic accuracy of mammography.

**2.1 Mammography** 

**2.2 Ultrasonography** 

(Liberman, 2000).

**2.3 Magnetic Resonance Imaging (MRI)** 

While breast cancer is still increasing in frequency, new diagnostic procedures must be available to challenge existing procedures to make diagnosis of breast cancer more accurate and reliable. DOT is one of the most important non-invasive and non-ionizing imaging modalities that are available for breast cancer diagnosis. DOT can be used to locate lesions within breast (Frangioni, 2008; Kepshire et al., 2007; Hawrysz et al, 2000). Despite promising results, there are several factors that limit the wide application of DOT for the imaging of breast tissue in clinic. First, the maximum depth of imaging in breast tissue is less than 15 mm. Secondly, the spatial resolution of DOT is less than one centimeter, that is not as good as mammography, ultrasonography or MRI. Because of these limitations, DOT is not a widely-accepted imaging modality for breast cancer (Kepshire et al., 2007; Hawrysz et al., 2000).

#### **2.5 Computed Tomography (CT)**

X-ray computed tomography (introduced into clinical practice in 1972) was the first of modern slice-imaging modalities. CT scan has several advantages including (1) unlimited depth penetration; (2) high spatial resolution; (3) short acquisition time (minutes); (4) moderately cheap and (5) ability of performing anatomical imaging. CT has some limitations including (1) sensitivity of CT scan decreases in early stage of breast cancer, (2) CT scan is associated with radiation exposure and should never be done in pregnant females because of radiation risk to the fetus, (3) CT is not very good at identifying pathology of soft tissues, (4) the dye used in CT is iodine based and is often a cause of allergy and (5) CT probably can not be used for molecular imaging and currently is just used for anatomical and functional imaging (Pysz et al., 2010).

#### **2.6 Measurement of tumor markers in blood**

Several biochemical compounds in the serum/plasma may act as the indicators of the presence, risk or prognosis of cancer. In patients with history of breast cancer, elevated tumor marker levels may represent cases of tumor relapse. It has been shown that increasing levels of tumor markers is associated with disease recurrence and may indicate the need for further investigations. Examples of tumor markers in blood including CA 15.3, CA 27.29, CA125, CEA and circulating tumor cells. While breast cancer blood marker tests are promising, they are not absolutely conclusive. When a breast cancer blood marker test comes back negative, it doesn't necessarily mean that the patient is free and clear of breast cancer and a positive result does not always mean that the cancer is growing (Merkle et al., 2009).

#### **2.7 Nuclear medicine**

As cited, each imaging method has strengths and weaknesses in terms of sensitivity, specificity, spatial and temporal resolution, contrast and cost. Therefore, the fundamental efforts for introduction and development of new methods for breast cancer diagnosis are requested. Nuclear medicine is defined as a branch of medicine that employs open radioactive sources, commonly referred to radionuclides, in diagnosis and treatment of diseases (Glasspool & Evans, 2000). The application of nuclear medicine techniques to study patients with breast cancer has recently raised its profile particularly in the investigation of indeterminate mammographic lesions and for overcoming limitations of MRI, US, CT and

Breast Cancer: Radioimmunoscintigraphy and Radioimmunotherapy 169

breast or by breast-conserving surgery often termed lumpectomy of cancer. If the tumor is detected at early stage before spreading, surgery alone might be sufficient to reach complete remission. When the tumor is detected after spreading with distant metastases, surgery is frequently used in combination with radiotherapy or chemotherapy (Keshtgar

In radiotherapy, also known as radiation therapy, high-energy ionizing radiation such as x or γ-rays is irradiated to the tumor tissues for killing the cancer cells. Radiation can be delivered via external radiation from a source outside the body directing to the tumor or by an internal radiation source (brachytherapy) which is positioned inside the body adjacent to or inside the tumor. Radiation must affect only cancer cells in the treated area and not normal cells. To treat secondary tumors and stopping growth of any remaining tumor cells, radiation therapy is often used in conjunction with other treatment modalities like

The use of cytotoxic chemotherapy, in both advanced and early stage of breast cancer, has made significant progress in the last decade (Hassan et al., 2010). Chemotherapy is a systemic breast cancer therapy and compared to surgery and radiation therapy, it has one advantage. It is able to eliminate cancer cells throughout the entire body. Chemotherapeutic agents currently approved for treatment of breast cancer are: anthracycline, alkaloids, topoisomerase inhibitors, alkylating agents, and antimetabolites. The important disadvantage of chemotherapy is side effects of drugs such as nausea, vomiting, fatigue, sore mouth, diarrhea, constipation and decreased blood cells count. These side effects can impact patient ability to tolerate treatment, maintain a healthy diet, stay active and enjoy a

Hormone therapy, also called "endocrine-based therapy", is a systemic treatment and plays an important role in breast cancer therapy. It is the first type of systemic treatment directed at a specific target, the hormone-dependent cancer cell, and may be referred to "targeted therapy" (Hind et al., 2007). The purpose of hormone therapy is to add, block or remove hormones. There are certain hormones that can attach to breast cancer cells and affect their ability to multiply such as tamoxifen, fareston, arimidex and so on (Jones& Buzdar, 2004). Hormone therapy may be used alone or in combination with radiation therapy. It is rarely used simultaneously, but is often used following chemotherapy. The benefits and side effects of the drugs relate only to the natural effects of the hormone itself and the hormonecancer cell interaction. For that reason, the typical side effects seen with chemotherapy are

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

not present with hormone or endocrine-based therapies (Hind et al., 2007).

et al, 2010).

**3.2 Radiotherapy** 

**3.3 Chemotherapy** 

**3.4 Hormone therapy** 

**3.5 Immunotherapy** 

chemotherapy and surgery (Luini et al., 2007).

good quality of life (Hassan et al., 2010).

DOT techniques (Berghammer et al., 2001). The differences in tumor biology such as blood flow, metabolism, concentration of specific receptors or differences in antigen expression are exploited in order to target radionuclides to the tumor tissue (Glasspool & Evans, 2000). The major advantage of nuclear medicine is that just picomolar concentrations of radiotracers are required to provide a measurable signal (Cook et al., 2003).
