Improved imaging of infections by avidin-induced clearance of 99mTc-biotin-PEG liposomes.
This article describes the preparation and optimization of biotin-polyethyleneglycol (PEG) liposomes and their application in experimental infection models to improve the scintigraphic imaging of infection and inflammation.


METHODS
Biotin was coupled to PEG-distearoylphosphatidylethanolamine (DSPE) and subsequently incorporated in the PEG liposomes. Biotinylated liposomes were radiolabeled with 99mTc-hydrazinonicotinamide. In vitro binding studies were performed to find the optimal biotin concentration in the liposomes. In rats the biodistribution of the 99mTc-biotin-PEG liposomes was compared with the biodistribution of normal (nonbiotinylated) 99mTc-PEG liposomes. Furthermore, in vivo studies in rats were performed to study both the effect of the biotin content and the optimal avidin dose for efficient clearance of the liposomes. Liposomes containing 0.5 or 1.0 mol% biotin-PEG-DSPE were compared in rats with a Staphylococcus aureus infection in the left calf muscle. Avidin was injected 4 h after injection of the liposomes.


RESULTS
Biotinylation of the liposomes did not affect their in vivo behavior. All biotin-PEG liposome formulations tested showed good in vitro avidin binding with 50% inhibitory concentrations ranging from 36 to 8 micromol/L. With avidin doses higher than 100 microg, both preparations rapidly cleared from the circulation. As a result, abscess-to-blood ratios increased 5-fold. To illustrate the potential of the avidin-induced clearance of radiolabeled PEG liposomes, we also studied the 99mTc-biotin-PEG liposomes in rabbits with a subcutaneous S. aureus abscess. The infection was visualized only after injection of 100 microg avidin.


CONCLUSIONS
This study shows that biotin-coated 99mTc-PEG liposomes in combination with the injection of avidin can lead to improved imaging of infection or inflammation localized especially in regions with high blood-pool activity.
Laverman
P
P
Department of Nuclear Medicine, University Hospital Nijmegen, The Netherlands.
Zalipsky
S
S
Oyen
W J
WJ
Dams
E T
ET
Storm
G
G
Mullah
N
N
Corstens
F H
FH
Boerman
O C
OC
D000038:Abscess / Q000000981:diagnostic imaging; D000818:Animals; D001360:Avidin; D019921:Biotinylation; D005260:Female; D008081:Liposomes; D008297:Male; D011092:Polyethylene Glycols; D011817:Rabbits; D011877:Radionuclide Imaging; D051381:Rats; D017208:Rats, Wistar; D013203:Staphylococcal Infections / Q000000981:diagnostic imaging*; D013667:Technetium
D008081:Liposomes; D001360:Avidin; D011092:Polyethylene Glycols; D013667:Technetium