Polymer-derivatized technetium 99mTc-labeled liposomal blood pool agents for nuclear medicine applications.
By using the lipophilic chelator, dipalmitoylphosphatidylethanolamine-diethylenetriaminetetraacetic acid (DPPE-DTTA), lipid vesicles may be prepared labeled on their surface with technetium 99m. When technetium-labeled vesicles were injected intravenously into rabbits, the half-life for clearance of the label from the circulation was less than 30 min. By further incorporating a synthetic phosphatidylethanolamine-monomethoxypoly(ethylene glycol) 5000 conjugate (PE-MPEG) the circulation half-life of the radiolabel was increased, liver uptake decreased and exchange of technetium from the vesicle surface suppressed, depending upon both the DPPE-DTTA and PE-MPEG content. For vesicles containing 20 mol% DPPE-DTTA, incorporation of PE-MPEG had no effect upon the circulation half-life of the radiolabel, however, for vesicles containing 2 mol% DPPE-DTTA, incorporation of more than 4 mol% PE-MPEG increased the circulation half-life of the label to more than 12 h. Less than 2 mol% PE-MPEG or 8 mol% ganglioside GM1 were, however, ineffective at increasing the circulation half-life of surface-bound technetium. It was shown that unilamellar lipid vesicles with DPPE-DTTA can be lyophilized in the presence of external sucrose, subsequently rehydrated with no change in vesicle size and labeled with technetium. It is suggested that polymer-derivatized, technetium-labeled vesicles may prove a useful substitute for technetium-labeled red blood cells as a vascular marker in various nuclear medicine procedures and that lyophilization/rehydration provides a possible route to realization of such vesicles in a pharmaceutically useful form.
Department of Radiology, University of British Columbia, Vancouver, Canada.
C
C
Tilcock
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QF
Ahkong
D
D
Fisher
D000818:Animals; D015195:Drug Design; D005677:G(M1) Ganglioside / Q000737:chemistry; D006207:Half-Life; D007205:Indium Radioisotopes / Q000008:administration & dosage; D008081:Liposomes / Q000737:chemistry / Q000493:pharmacokinetics; D004369:Pentetic Acid / Q000031:analogs & derivatives / Q000737:chemistry; D010714:Phosphatidylethanolamines / Q000737:chemistry; D011092:Polyethylene Glycols / Q000737:chemistry; D011817:Rabbits; D013667:Technetium / Q000008:administration & dosage
D007205:Indium Radioisotopes; D008081:Liposomes; D010714:Phosphatidylethanolamines; C060068:diethylenetriaminetetraacetic acid; C007510:1,2-dipalmitoyl-3-phosphatidylethanolamine; D005677:G(M1) Ganglioside; D011092:Polyethylene Glycols; D013667:Technetium; D004369:Pentetic Acid; C028210:monomethoxypolyethylene glycol