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

Synthesis of a radiolabeled diglyceride, 3-[F-18]fluoro-1,2-dipalmitoylglycerol [[F-18]fluorodipalmitin ([F-18]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 nucteophilic 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 [F-18]FDP with a decay-corrected yield of 70 +/- 8% (n=4). PET imaging and biodistribution studies were performed with free [F-18]FDP and liposome-incorporated [F-18]FDP. Freely injected [F-18]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 [F-18]FDP was incorporated into the phospholipid bilayer, it could potentially be used for radiolabeling a variety of lipid-based drug carriers. (c) 2007 Elsevier Inc. All rights reserved.