Biodistribution and computed tomography blood-pool imaging properties of polyethylene glycol-coated iopromide-carrying liposomes.
OBJECTIVE
Surface-modified contrast-carrying liposomes potentially are useful as computed tomography (CT) blood-pool agents. The biodistribution and CT-imaging behavior of conventional as well as polyethylene glycol (PEG)-coated iopromide-carrying liposomes were tested. Two different types of PEG-ylated lipids were used to demonstrate possible differences.


METHODS
Iopromide-containing liposomes were prepared by a continuous high-pressure extrusion method and subsequently PEG-ylated by simple mixing with either DSPE-PEG2000 or CHHS-PEG2000. The resulting liposomes were investigated in rats (biodistribution) and rabbits (imaging).


RESULTS
Surface modification with CHHS-PEG consistently resulted in less effective stabilization of liposomes in the blood than with DSPE-PEG. In the biodistribution study, no significant differences in blood concentration could be found 1 hour after injection between the different formulations at a dose of 250 mg total iodine/kg body weight (approximately 500 mg lipid/kg). At this dose, the unmodified as well as the DSPE-PEG liposomes displayed prolonged blood circulation with CT density differences above 70 Hounsfield units (aorta) for up to 20 minutes (n = 1).


CONCLUSIONS
DSPE-PEG-coated and unmodified liposomes proved to be useful for CT blood-pool imaging displaying favorable imaging properties. Future studies will have to demonstrate whether PEG-ylation offers diagnostic or toxicologic advantages over conventional vesicles in this indication.
Sachse
A
A
Research Laboratories of Schering AG, Berlin, Germany.
Leike
J U
JU
Schneider
T
T
Wagner
S E
SE
Rössling
G L
GL
Krause
W
W
Brandl
M
M
D000818:Animals; D001810:Blood Volume; D003287:Contrast Media / Q000493:pharmacokinetics*; D003692:Delayed-Action Preparations; D004337:Drug Carriers; D007472:Iohexol / Q000031:analogs & derivatives* / Q000493:pharmacokinetics; D008081:Liposomes; D008099:Liver / Q000000981:diagnostic imaging / Q000378:metabolism*; D008297:Male; D011092:Polyethylene Glycols / Q000493:pharmacokinetics*; D011817:Rabbits; D051381:Rats; D017208:Rats, Wistar; D013154:Spleen / Q000000981:diagnostic imaging / Q000378:metabolism*; D014018:Tissue Distribution; D014057:Tomography, X-Ray Computed / Q000379:methods*
D003287:Contrast Media; D003692:Delayed-Action Preparations; D004337:Drug Carriers; D008081:Liposomes; D011092:Polyethylene Glycols; D007472:Iohexol; C038192:iopromide