Detection of Altered Adhesion Molecule Expression in Experimental Tumors by a Radiolabeled Monoclonal Antibody

摘要

Adhesion molecules play a major role in the processes of invasion and metastasis of malignant tumors. Their expression within tumors has been reported to be quantitatively and qualitatively altered according to the invasiveness and metastatic potential of the tumor. The present study tested whether the intratumoral expression of integrin α3 can be detected by a radiolabeled monoclonal antibody. The in vitro hinding study with four different human cancer cells showed that radioiodinated GA17 antibody recognizing integrin “3 bound specifically to these cells to varying degrees, according to the antigen density on each cell. The biodistribution study with ¹²⁵I– and ¹¹¹In–labeled antibodies showed specific localization of radiolabeled GA17 to the xenografts. However, the in vivo tumor localization was not proportional to the antigen density calculated in vitro, and antibody metabolism varied among the tumors, as was also confirmed by in vitro radionuclide retention assay. The intratumoral distribution of radioactivities varied reflecting the antigen expression within the tumor. These results indicate that 1) integrin α3 was expressed in various kinds of tumors and could he localized by the radiolabeled antibody, and 2) the expression of integrin “3 and the metabolism of the radiolabeled antibody after binding to the antigen within the tumor were variable among the tumors, which affected the radionuclide distribution characteristics. The expression of adhesion molecules within these tumors was noninvasively detected by a radiolabeled antibody. It may be possible to use integrin a3, when it is overexpressed, as a target of therapy with antibodies radiolabeled with a or β emitters.