**11.13 CockTails**

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

#### **11.14 Increasing tumor uptake**

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

#### **11.15 Reducing kidney uptake**

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 unaffected (Behr et al., 1995).
