Long-circulating liposomes radiolabeled with [¹⁸F]fluorodipalmitin ([¹⁸F]FDP)

Synthesis of a radiolabeled diglyceride, 3-[¹⁸F]fluoro-1,2-dipalmitoylglycerol [[¹⁸F]fluorodipalmitin ([¹⁸F]FDP)], and its potential as a reagent for radiolabeling long-circulating liposomes were investigated. The incorporation of ¹⁸F into the lipid molecule was accomplished by nucleophilic substitution of the p-toluenesulfonyl moiety with a decay-corrected yield of 43±10% (n=12). Radiolabeled, long-circulating polyethylene-glycol-coated liposomes were prepared using a mixture of 1,2-dipalmitoyl-sn-glycero-3-phosphocholine, cholesterol, 1,2-distearoyl-sn-glycero-3-phosphoethanolamine-N-[methoxy(polyethyleneglycol)-2000] ammonium salt (61:30:9) and [¹⁸F]FDP with a decay-corrected yield of 70±8% (n=4). PET imaging and biodistribution studies were performed with free [¹⁸F]FDP and liposome-incorporated [¹⁸F]FDP. Freely injected [¹⁸F]FDP had the highest uptake in the liver, spleen and lungs. Liposomal [¹⁸F]FDP remained in blood circulation at near-constant levels for at least 90 min, with a peak concentration near 2.5%ID/cc. Since [¹⁸F]FDP was incorporated into the phospholipid bilayer, it could potentially be used for radiolabeling a variety of lipid-based drug carriers.