974 New developments of nuclear medicine in diagnosis and treatment: The pretargeting approach

Abstract

Specific targeting of radioactive agents to tumor cells has been a major goal of the <i>in vivo</i> use of monoclonal antibodies (MoAb) for diagnostic and therapeutic purposes. However, only a relatively small amount of the injected dose of MoAbs is bound by the tumor, while MoAb conjugated to radioisotope keep circulating in the blood stream and in normal tissue. These considerations have led to strategies of tumor pretargeting, where MoAb and radiolabel are administered separately. One of these strategies is based on the avidin-biotin system. With the so-called three-step method, injection of non-radioactive biotinylated MoAbs (first step) is followed after I day by ″cold″ avid in (second step). If radioactively labelled biotin is now administered (third step), it binds selectively to avidin and therefore to the tumour, including colon and lung cancers, gliomas, ocular and cutaneous melanomas and apudomas. The method has shown to be safe, reliable and of clinical utility since an overall sensitivity of 88% with 94% specificity and 84% accuracy was demonstrated. These encouraging results have prompted us to initiate a therapy trial using biotin-LC-DOTA labeled with Y-90.