Optimization of technetium-99m-labeled PEG liposomes to image focal infection: effects of particle size and circulation time.
In previous studies we have shown that liposomes sterically stabilized with polyethylene glycol (PEG), preferentially localize in infectious and inflammatory foci. In this study, we further optimized the formulation of PEG liposomes for infection imaging in a rat model.


METHODS
The biodistribution and imaging characteristics of different liposomal formulations labeled with 99mTc were determined in rats with S. aureus infection of the left calf muscle. The influence of liposomal size (mean diameter varying from 90 nm to 220 nm) as well as circulation time (modulated by inclusion of 0-10 mole% phosphatidylserine) were studied.


RESULTS
The smallest liposomes displayed improved characteristics for infection imaging: 90-nm liposomes revealed the highest abscess uptake (1.6% +/- 0.4% ID/g, 24 hr postinjection) in combination with the lowest splenic accumulation (6.9% +/- 0.7% ID/g, 24 hr postinjection) as compared to the larger sized preparations. Enhanced abscess-to-blood ratios (4.0 versus 1.3 at 24 hr postinjection) were obtained by including 1.0 mole% phosphatidylserine in the lipid bilayer of the PEG liposomes. However, enhanced blood clearance of these liposomes reduced their absolute abscess uptake.


CONCLUSIONS
These results indicate that the in vivo behavior of PEG liposomes can be modulated to optimize their characteristics for infection imaging.
Boerman
O C
OC
Department of Nuclear Medicine, University Hospital Nijmegen, The Netherlands.
Oyen
W J
WJ
van Bloois
L
L
Koenders
E B
EB
van der Meer
J W
JW
Corstens
F H
FH
Storm
G
G
D000038:Abscess / Q000000981:diagnostic imaging*; D000818:Animals; D004337:Drug Carriers; D005490:Focal Infection / Q000000981:diagnostic imaging*; D008081:Liposomes; D008297:Male; D008657:Metabolic Clearance Rate; D018482:Muscle, Skeletal / Q000000981:diagnostic imaging* / Q000378:metabolism; D010316:Particle Size; D011092:Polyethylene Glycols / Q000008:administration & dosage* / Q000493:pharmacokinetics; D011877:Radionuclide Imaging; D051381:Rats; D017208:Rats, Wistar; D013667:Technetium / Q000493:pharmacokinetics; D014018:Tissue Distribution
D004337:Drug Carriers; D008081:Liposomes; D011092:Polyethylene Glycols; D013667:Technetium