**12. Conclusion**

188 12 Chapters on Nuclear Medicine

(Dearling & pedley, 2007). In addition, it allows the creation of bispecific antibody molecules that can target two different antigens simultaneously (Sergey et al., 2008). During the last decade, several techniques in multivalency engineering have been developed. Each of these strategies proposed to link monovalent domains and to produce multivalent antibody, obviously has some advantages in some special cases, but none of them is universal. The advantages of tumor targeting with multivalent antibody derivatives have been investigated for scFv dimers, prepared as disulfide-linked dimers of scFv (Adams et al., 1995), non-covalent diabodies (Kortt et al., 2001) and some other bi(multi)valent variants of recombinant antibody fragments (Kubetzko et al.,2006; Shahied et al., 2004; Willuda et al., 2001). In most cases, dimeric/divalent antibodies showed significant improvement of their pharmacokinetics and

One problem of RIS is the existence of diversity of epitopes on surface tumor cells that reduces uptake radioactivity in tumor. An alternative approach to improve the uptake of radioactivity by the target is using cocktails of several radiolabelled antibodies that recognize different epitopes or antigens on the same tumor. However, some of the experiments indicated positive results by using cocktails, other experiments showed that the mAbs of cocktails competed to bind to epitopes with each other and reduce the efficacy of

By increasing the level of antigen expression, diagnosis and therapy based on targeting can be improved. For example, hyperthermia can increase the amount of presenting antigen in a tumor (Wilder et al., 1993). Furthermore, several cytokines such as interferon alpha and interleukin-6 have been found to upregulate the expression of cell surface antigens including histocompatibility antigens and tumor associated antigens such as carcinoembryonic antigen (CEA). In both *in vivo* and *in vitro* studies an improved antibodyuptake has been demonstrated as a result of the administration of vasoactive peptides and cytokines such as IL-2 or external beam radiation therapy may result in a specific increased vascular permeability at the tumor site and thus an increased antibody uptake (Guadagni, et al., 1990). Structural modification (e.g., PEGylation) and residue mutation are both useful strategies in reducing chemically or physically derived nontarget organ uptake of Abs, but these methods do not reduce the uptake due to receptor expression within nontarget organs.

Elevated renal uptake and prolonged retention of radiolabeled antibody is a problem in the therapeutic application of such agents (Dearling & pedley, 2007). Because of the negative charge of the basement membrane of the glomeruli, positively charged catabolites of the radiopharmaceutical may be retained in the kidney, increasing the toxic absorbed dose to this radiosensitive organ (Dearling & pedley, 2007). The result of some studies demonstrated that lysine, histidine and arginine were effective in reducing the renal uptake of radiopharmaceutical and lysine was the most effective (Lin et al., 2007). In these studies it has been shown that renal retention can also be minimized by the administration of lysine, a cationic amino acid, whereas the uptake in all other organs as well as the tumor remains

the mixture to less than that of one antibody used alone (sergey et al., 2008).

These are research areas of high interest (Boswell & Brechbiel, 2007).

biodistribution over monomers (Sergey et al., 2008).

**11.13 CockTails** 

**11.14 Increasing tumor uptake** 

**11.15 Reducing kidney uptake** 

unaffected (Behr et al., 1995).

In recent years, significant developments in the application of targeted imaging and therapy have taken place in nuclear medicine. This chapter suggests that optimization of radioimmunoscintigraphy and radioimmunotherapy methods is still possible and emphasizes that these technologies are continuing to progress and are close to become routine modalities in the identification of breast cancer sites and its therapy. The development of effective imaging and therapy of breast cancer relies to a great extent on the development of effective carriers and target agents that can deliver radionuclids to the cancer cells. These agents should be able to carry a large load of radionuclids and selectively deliver them to the cancer cells with high accuracy to achieve effective cancer cells death without inducing nonspecific toxicity. This means that the use of new targeting agents such as peptides and affibodies can provide promising results. Liposomes, dendrimers, micelles and nanoparticles present large families of carriers that can be exploited for delivery of radionuclids and they can be further improved to diagnose and therapy of breast cancer in the future. The research in the field of targeted imaging and therapy will help us to avoid unnecessary costs and potentially allow these new methods to be available for the majority of patients who need them, leading to better quality and quantity of life.
