Abstract
Polylysine (PL) was used to prepare derivatives with chelating properties. For this purpose PL was modified with cyclic or mixed anhydride of diethylene triamine pentaacetic acid (DTPA) or with deferoxamine (DFA). The modification permits to introduce into single polylysine molecule up to 100 DTPA residues (for 55 kDa polylysine), capable of firm binding metals like In or Gd, which are widely used in radioscintigraphy and NMR-tomography. To make polymeric chelates specific towards target areas, they were conjugated with specific monoclonal antibodies. Special technique of antibody modification with chelating polymer has been developed, permitting to bind whole antibody or its Fab with the polymer via minimal number of chemical bonds and with minimal loss in immunoreactivity. Very high specific radioactivity was achieved for antibodies labeled with 111 In: ca. 100 μCi per 1 μg of protein. In vivo studies were performed in rabbits with experimental myocardial infarction, utilizing monoclonal antibodies against cardiac myosin, labeled with 111In via DTPA-containing PL-based chelating polymers. Good accumulation of antibody-polymer conjugates in infarcted areas was demonstrated (target-to-normal ratio can reach several dozens).
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