CHELATING POLYMER-MODIFIED MONOCLONAL-ANTIBODIES FOR RADIOIMMUNODIAGNOSTICS AND RADIOIMMUNOTHERAPY

Polylysine (PL) was used to prepare derivatives with chelating propert ies. For this purpose PL was modified with cyclic or mixed anhydride o f diethylene triamine pentaacetic acid (DTPA) or with deferoxamine (DF A). The modification permits to introduce into single polylysine molec ule up to 100 DTPA residues (for 55 kDa polylysine), capable of firm b inding metals like In or Gd, which are widely used in radioscintigraph y and NMR-tomography. To make polymeric chelates specific towards targ et areas, they were conjugated with specific monoclonal antibodies. Sp ecial technique of antibody modification with chelating polymer has be en developed, permitting to bind whole antibody or its Fab with the po lymer via minimal number of chemical bonds and with minimal loss in im munoreactivity. Very high specific radioactivity was achieved for anti bodies labeled with In-111: ca. 100 muCi per 1 mug of protein. In vivo studies were performed in rabbits with experimental myocardial infarc tion, utilizing monoclonal antibodies against cardiac myosin, labeled with In-111 via DTPA-containing PL-based chelating polymers. Good accu mulation of antibody-polymer conjugates in infarcted areas was demonst rated (target-to-normal ratio can reach several dozens).