Long-circulating liposomes radiolabeled with [18F]fluorodipalmitin ([18F]FDP).
Synthesis of a radiolabeled diglyceride, 3-[(18)F]fluoro-1,2-dipalmitoylglycerol [[(18)F]fluorodipalmitin ([(18)F]FDP)], and its potential as a reagent for radiolabeling long-circulating liposomes were investigated. The incorporation of (18)F 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 [(18)F]FDP with a decay-corrected yield of 70+/-8% (n=4). PET imaging and biodistribution studies were performed with free [(18)F]FDP and liposome-incorporated [(18)F]FDP. Freely injected [(18)F]FDP had the highest uptake in the liver, spleen and lungs. Liposomal [(18)F]FDP remained in blood circulation at near-constant levels for at least 90 min, with a peak concentration near 2.5%ID/cc. Since [(18)F]FDP was incorporated into the phospholipid bilayer, it could potentially be used for radiolabeling a variety of lipid-based drug carriers.
Marik
Jan
J
Department of Biomedical Engineering, University of California Davis, Davis, CA 95616, USA.
Tartis
Michaelann S
MS
Zhang
Hua
H
Fung
Jennifer Y
JY
Kheirolomoom
Azadeh
A
Sutcliffe
Julie L
JL
Ferrara
Katherine W
KW
D000818:Animals; D004075:Diglycerides / Q000737:chemistry*; D004337:Drug Carriers / Q000737:chemistry*; D008055:Lipids / Q000737:chemistry; D008081:Liposomes / Q000097:blood* / Q000737:chemistry / Q000493:pharmacokinetics*; D008297:Male; D008657:Metabolic Clearance Rate; D008694:Methamphetamine / Q000031:analogs & derivatives* / Q000097:blood / Q000493:pharmacokinetics; D009928:Organ Specificity; D049268:Positron-Emission Tomography / Q000379:methods; D019275:Radiopharmaceuticals / Q000097:blood / Q000493:pharmacokinetics; D051381:Rats; D011916:Rats, Inbred F344; D014018:Tissue Distribution; D014915:Whole-Body Counting
C534455:3-fluoro-1,2-dipalmitoylglycerol; D004075:Diglycerides; D004337:Drug Carriers; D008055:Lipids; D008081:Liposomes; D019275:Radiopharmaceuticals; C092352:1-fluoro-1-deoxyephedrine; D008694:Methamphetamine