**10. Technical limitations of radioimmunoscintigraphy and radioimmunotherapy**

Although this conceptually simple technique has been investigated and refined for almost 50 years, it still has inherent limitations. In the present part, the problems of imaging and therapy of breast cancer by radioimmunoscintigraphy and radioimmnotherapy methods are discussed.

Breast Cancer: Radioimmunoscintigraphy and Radioimmunotherapy 185

applied successfully for radioimmunoimaging, because the pretargeted antibody is nontoxic. High doses can be administered to saturate antigenic sites at the tumor. Pretargeting strategies for RIT have been applied to achieve higher intratumor concentration of isotope than achieved by conventional RIT (Kraeber–Bodere et al., 2009). The simplest form of pre-targeting is to use a second antibody reagent to clear blood background activity, hence improving the signal:noise ratio and the quality of the image. Immune complexes formed by a second antibody are rapidly removed from the circulation by the reticuloendothelial system, particularly in the liver. In the alternative approach, the administration of antibody and radiolabel are separated. Antibody is allowed to localize to the tumor and sufficient time is allowed for antibody clearance from the blood and non-target tissues (Dearling & pedley, 2007). Radioisotope is then injected separately in a form which can be readily captured by the tumor bound antibody. The approaches using streptavidin/biotin binding systems raised much interest, because the affinity of streptavidin for biotin is exceptionally high (Gruaz-Guyon et al., 2005). In this strategy, the high affinity of the avidin:biotin system is used to capture radiolabeled small molecules from the blood as a two-step imaging method. Antibody-avidin conjugate is injected and allowed to be localized to the tumor and cleared from the blood (Dearling & pedley, 2007). Radioactive avidin is then injected which localizes the tumor by taking advantage of the high affinity and specificity of avidin for biotin (Roland

Dose fractionation has been proposed as a method to improve the therapeutic effect of radioimmunotherapy (Dearling & pedley, 2007, Denardo et al., 2002). Fractionated radioimmunotherapy may improve therapeutic outcome by decreasing heterogeneity of the dose delivered to the tumor and by decreasing hematologic toxicity, thereby allowing an increased amount of radionuclide that can be administered (Linden et al,. 2005) . A variety of fractionation regimens have been developed and the studies have reported both against and in its favour (Goel et al., 2001; Buchsbaum et al., 1995; Pedley et al., 1993; Schlom et al.,1990; Beaumier et al., 1991). This technique has several advantages including more uniform distribution of mAb and radiation dose, patient-specific radionuclide and radiation dose, control toxicity by titration of an individual patient, reduced toxicity, increased tumor radiation and efficacy and prolongation of tumor response (Violet, 2008). This technique has some disadvantages including lower radiation dose rate, complex strategy to implement, treatment interruption, increased cost and potential delay in tumor regression (Dearling &

Kinetic differences in specific and non-specific uptake of radioactivity provide an opportunity to image at a time when the T/B ratio is optimal. Background radioactivity falls with time due to excretion and decay of the radioisotope. Tumor radioactivity also falls with time, but not as fast as the background. The optimum time for RIS is dependent on the

If the background is labeled using a non-specific antibody, the background signal can then be subtracted from the results of RIS (Sergides et al., 1999; Goldenberg et al., 1978). It should

selected antibody and radioisotope and detection method (Sergides et al., 1999).

et al., 2010, Dearling & pedley, 2007).

**11.2 Dose fractionation** 

pedley, 2007).

**11.3 Delayed imaging** 

**11.4 Background subtraction** 
