TARGETED DELIVERY OF DIAGNOSTIC AGENTS BY SURFACE-MODIFIED LIPOSOMES

Surface-modified LS have been used for the specific delivery of heavy metal-based imaging agents. The liposome surface was modified with PEG , AMmAb, Dext-SA, chelating agent DTPA-PE, and with NGPE-modified chel ating polymer: DTPA-NPLL-NGPE. The hypothesis is suggested attempting to explain the phenomenon of long circulation of PEG-coated LS from th e point of view of statistical propel-ties of flexible polymer molecul e in solution. Direct experiments using fluorescent labels were perfor med to prove the hypothesis. The calculations performed on the basis o f the hypothesis were designed to find the optimal concentration of PE G on the LS surface, and suggested that it not only provides a protect ive effect but also does not create steric hindrances for the surface- immobilized mAb. As a result, long circulating targeted ILS have been prepared. Intravenously administered In-111-labelled PEG-AMmAb-LS were targeted to the area of experimental myocardial infarction in rabbits under gamma-scintigraphic control. Infarct-to-normal ratios of In-111 radioactivity of about 20 were achieved. PEG-and Dext-modified liposo mes with surface-incorporated Gd-labelled DTPA-PE or DTPA-NPLL-NGPE we re used for the subcutaneous administration and subsequent NMR-imaging of lymph nodes in rabbits. Two mechanisms of MR-signal enhancement we re found for the surface-modified Gd-containing LS: the increase in si gnal intensity due to the increase in water quantity in the vicinity o f Gd atoms because of PEG-associated water; and better lymph node accu mulation of Dext-LS via receptor-mediated endocytosis. Surface modific ation of LS opens the possibilitiy for targeted delivery of heavy meta l-based imaging agents.