ATTACHMENT OF TC-99M TO LIPID VESICLES CONTAINING THE LIPOPHILIC CHELATE DIPALMITOYLPHOSPHATIDYLETHANOLAMINE DTTA

The binding of Tc-99m to negatively-charged and neutral unilamellar lipid vesicles was investigated in the absence and presence of the ligand diethylenetriaminepentaacetic acid (DTPA) covalently attached to the headgroup of phosphatidylethanolamine at the surface of the membrane. Even in the absence of DTPA on the membrane surface, Tc-99m reduced by Sn bound to the membrane surface but rapidly dissociated from the vesicles in the presence of plasma in vitro. When DTPA was present on the membrane surface, dissociation of Tc-99m from the vesicle surface in plasma was much reduced. The dissociation of Tc-99m from the surface of negatively-charged vesicles was less than for neutral vesicles in the absence of ligand but was markedly greater than for vesicles containing the ligand DTPA, suggesting that the binding of Tc-99m to vesicles with surface-attached DTPA could not be explained solely on the basis of the negative charge provided by the DTPA. In vitro experiments using C-14-labeled lipids as well as in vivo imaging studies indicated that dissociation of Tc-99m from the surface of the vesicle did not arise predominantly because of lipid exchange with plasma components or due to cleavage of Tc-99m-DTPA from the vesicle surface. For vesicles with surface-attached DTPA, Tc-99m dissociation from the vesicle surface in plasma was further reduced by addition of the antioxidant ascorbate.