**7.2.2 Single photon emission tomography**

Single photon emission computed tomography (SPECT) is a sensitive nuclear imaging technique that provides a 3D spatial distribution of single-photon emitting radionuclide within the body (Gomes et al., 2010). Multiple 2D images, also called projections, are acquired from multiple angles around the patient and subsequently reconstructed using the reconstruction imaging methods to generate cross-sectional images of the internal distribution of the injected molecules (Wernick, & Aarsvold,2004). Because of the isotropic emission of γ-rays, a geometric collimation is needed to restrict the travelling direction of the emitted γ-rays from the body, through the use of lead collimators. In clinical systems, collimators typically have many parallel holes that produce no magnification. The photons that travel in other directions than those specified by the aperture of collimator are absorbed and do not contribute to the image, which reduces the detection efficiency and sensitivity of SPECT as compared to PET (Madsen, 2007). SPECT have several advantages including (1) whole body imaging, (2) quantitative molecular imaging and (3) can be combined with CT for preparing anatomical information. The disadvantages of this method are radiation exposure, low spatial resoulation (0.3-1 mm, 12-15 mm3) and long acquisition time (Pysz et al., 2010).

Breast Cancer: Radioimmunoscintigraphy and Radioimmunotherapy 181

technology, a method that made it possible to produce large quantities of monoclonal antibodies with high purity and reproducibility (Kohler & Milstein, 1975). Since then, numerous antigen-antibody systems have been established and several of the antibodies have been taken to clinical trials. Radioimmunotherapy is a method of selectively delivering radionuclides with toxic emissions to cancer cells, while reducing the dose to normal tissues. Using mAbs labeled with radionuclides has two major advantages over the application of mAbs conjugated with either drugs or toxins. Firstly, tumor cells not expressing the target antigen can still be sterilized by the so-called crossfire phenomenon, i.e., radiation energy emitted by radionuclides bound to antibodies targeting adjacent tumor cells. Secondly, radionuclides are not subject to multidrug resistance. Although promising, RIT has been less effective for solid tumors, in part because they are less radiosensitive. However, early micrometatasis of breast cancer have been demonstrated to be radiosensitive (Koppe et al., 2005). On the other hand, an advantage of RIT is that it can target small metastatic lesions that are undetected by conventional scanning and would otherwise remain untreated. In addition,

RIT is able to target multiple metastases throughout the body in a single treatment.

disseminated cells is considered (Boswell & Brechbiel, 2007).

4. **Other parameters:** radioisotope availability and its cost.

The selection of a radionuclide for cancer treatments depends on several parameters including: 1. **Physical parameters**: The type of radiation emitted by the radionuclide, required energy necessary for therapy and half-life of the radionuclide are physical parameters that must be considered. The type of radiation and the content of its energy are important factors that determine what radionuclide is suitable for killing of single disseminated cells, small metastases or large cancer tissues. The physical half-life of the radionuclides should preferably be in the same order of magnitude as the biological half-life. A too long physical half-life increases the necessary amount of radionuclide to be delivered to the tumor cells to allow the reasonable amounts of decays before excretion. A shorter physical half-life, on the other hand, will not give enough time for the targeting process to take place. It seems reasonable to assume that the most suitable physical half-lives ranges from a few hours up to some days when targeting of

2. **Chemical parameters**: The chemical parameters are as follow: achievable specific activity, stability of the radionuclide/antibody complex after labeling and that the labeling procedure must not interfere with the immunological activity of the antibody. 3. **Biological parameters:** tumor type, size and location, antibody kinetics, antigen density and heterogeneity and antigenicity are the most important biological parameters.

Three main categories of radionuclides have been investigated for their potential therapeutic characterisation in radioimmunotherapy including β-particle emitters, α-particle emitters

So far, the vast majority of preclinical and clinical studies have been made to use β-emitting radionuclides such as 131I, 90Y, 186Re and 188Re. These radionuclides have a tissue range of about several millimeters. This can create a ''cross fire'' effect, so that antigen or receptor negative cells in a tumor can also be treated. High energy B-particles are not efficient for killing of single disseminated cells or small metastases. So, β-particle therapy is preferred for

**8.1 Radionuclides for treatment** 

and auger electron cascades.

large tumors (Boswell & Brechbiel, 2007).

**1. β-particle emitters** 
