99mTc-labeling of lipid vesicles containing the lipophilic chelator PE-DTTA: effect of tin-to-chelate ratio, chelate content and surface polymer on labeling efficiency and biodistribution behavior.
When injected intravenously, lipid vesicles labeled with 99mTc by means of a lipophilic chelator dipalmitoylphosphatidylethanolamine-diethylenetriaminetetraacetic acid (PE-DTTA) are rapidly accumulated by the mononuclear phagocytic system (MPS). By derivatizing the membrane surface with the lipid-polymer complex dipalmitoylphosphatidylethanolamine-monomethoxy polyethylene glycol 5000 (PE-MPEG), MPS uptake can be suppressed and loss of 99mTc label from the lipid surface reduced depending upon both PE-DTTA and PE-MPEG content. For vesicles containing 20% PE-DTTA, addition of PE-MPEG makes no difference to their rate of clearance from the circulation. However for vesicles containing 2% PE-DTTA, addition of more than 0.8% PE-MPEG increases circulation half-life, suppresses liver uptake and reduces renal clearance of the 99mTc label. The molar ratio of reducing agent (Sn) to chelator (PE-DTTA) is critical to efficient and reproducible labeling. For vesicles containing 2% PE-DTTA at a lipid concentration of 100 mM, a Sn/DTTA ratio of 0.35 gives close to optimal labeling. Variation in the Sn/DTTA ratio by a factor of two negatively impacts upon both labeling efficiency in vitro and circulation half-life in vivo. Potential uses for technetium-labeled lipid vesicles with extended circulation half-life are discussed.
Tilcock
C
C
Department of Radiology, University of British Columbia, Vancouver, Canada.
Ahkong
Q F
QF
Fisher
D
D
D000818:Animals; D002614:Chelating Agents / Q000737:chemistry*; D007553:Isotope Labeling; D015609:Organotechnetium Compounds / Q000737:chemistry* / Q000493:pharmacokinetics; D010084:Oxidation-Reduction; D004369:Pentetic Acid / Q000031:analogs & derivatives* / Q000737:chemistry / Q000493:pharmacokinetics; D010714:Phosphatidylethanolamines / Q000737:chemistry* / Q000493:pharmacokinetics; D011108:Polymers; D011817:Rabbits; D014001:Tin / Q000737:chemistry*; D014018:Tissue Distribution
D002614:Chelating Agents; D015609:Organotechnetium Compounds; D010714:Phosphatidylethanolamines; D011108:Polymers; C060068:diethylenetriaminetetraacetic acid; C007510:1,2-dipalmitoyl-3-phosphatidylethanolamine; D014001:Tin; D004369:Pentetic Acid