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

Abstract

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.