OPTIMIZATION OF TC-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 formul ation of PEG liposomes for infection imaging in a rat model. Methods: The biodistribution and imaging characteristics of different liposomal formulations labeled with Tc-99m were determined in rats with S. aure us infection of the left calf muscle. The influence of liposomal size (mean diameter varying from 90 nm to 220 nm) as well as circulation ti me (modulated by inclusion of 0-10 mole% phosphatidylserine) were stud ied. Results: The smallest liposomes Group displayed improved characte ristics for infection imaging: 90-nm liposomes revealed the highest ab scess 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 postin jection) as compared to the larger sized preparations. Enhanced absces s-to-blood ratios (4.0 versus 1.3 at 24 hr postinjection) were obtaine d by including 1.0 mole% phosphatidylserine in the lipid bilayer of th e PEG liposomes. However, enhanced blood clearance of these liposomes reduced their absolute abscess uptake. Conclusion: These results indic ate that the in vivo behavior of PEG liposomes can be modulated to opt imize their characteristics for infection imaging.