Antibodies conjugated with radioisotopes are being used for imaging and therapy of tumors. The effectiveness of these approaches depends on the tumor/non-tumor localization ratio that is achieved. This project is to further develop and establish a new method of antibody localization in which the tumor/non-tumor ratio is enhanced. Four distinct factors have contributed to the development of this approach: (1) the use of """"""""residualizing"""""""" radiolabels, which are trapped inside the cell after catabolism of the antibody to which they are attached. In this way, isotope that reaches the tumor will stay there longer; (2) use of a rapid clearance mechanism to clear the antibody conjugate from the blood at a selected time, approximately two days after injection; (3) use of a clearing agent that delivers the conjugate to hepatocytes, selectively; and (4) use of a radiolabel that is rapidly excreted from hepatocytes via bile. As determined in previous studies, a potential label for this approach is 111-In-benzyl-DTPA, and a potential clearing agent is galactosylated streptavidin, used in conjunction with biotinylated antibody. This strategy will be applied to various tumor types, and various antibodies, in order to establish its general applicability. The tumor xenograft models to be tested include lung, colon, and medullary thyroid carcinoma grown in nude mice. This approach takes advantage of the inherent properties of antibodies as imaging agents, namely their high avidity for target cells and their slow rate of blood clearance (normally), and is expected to produce higher tumor/non-tumor ratios than are obtained by most other methods. Direct comparisons with two other popular methods will be performed, to confirm any differences observed. This approach is believed to be readily applicable to patients.
| Govindan, Serengulam V; Griffiths, Gary L; Michel, Rosana B et al. (2002) Use of galactosylated-streptavidin as a clearing agent with 111In-labeled, biotinylated antibodies to enhance tumor/non-tumor localization ratios. Cancer Biother Radiopharm 17:307-16 |
| Ong, G L; Elsamra, S E; Goldenberg, D M et al. (2001) Single-cell cytotoxicity with radiolabeled antibodies. Clin Cancer Res 7:192-201 |
