CHELATING POLYMER-BASED IMMUNOCONJUGATES - NEW AGENTS FOR DIAGNOSTIC-IMAGING

New family of polymers is synthesized for labeling proteins (antibodie s) with multiple heavy metal ions for the use in gamma- and MR-imaging . Polylysine of different molecular weight was used in the majority of experiments, modified with multiple chelating moeities such as diethy lenetriamine pentaacetic acid. The modification permits to introduce i n a single polymer molecule (M(W) = 55 kDa) up to 100 chelating units able to firmly bind metals such as In, Gd, Mn, Tc, Re and others, whic h are widely used in radioscintigraphy and NMR-tomography. To make pol ymeric chelates specific towards target areas, they were conjugated wi th monoclonal antibodies. Special technique of antibody modification w ith chelating polymers was developed, permitting to bind whole antibod y or its Fab fragment with the polymer via minimal number of covalent bonds and with minimal loss in immunoreactivity. In vitro studies with radiometals demonstrated extremely high labeling efficacy of antibody : in case of In-111 the specific radioactivity achieved was up to 100 mCi per mg protein in comparison with 3 to 5 mCi per mg as obtained us ing traditional labeling protocols. In vivo studies in rabbits with ex perimental myocardial infarction and in mice with implanted human brea st tumor demonstrated fast and quantitative label accumulation in targ et areas. Amphiphilic derivatives of chelating polymers have been synt hesized able to incorporate into phospholipid membranes. Liposomes wit h surface-incorporated Gd-loaded chelating polymers have been successf ully used for MR-imaging of lymph nodes in rabbits.