Improved imaging of infections by avidin-induced clearance of Tc-99m-biotin-PEG liposomes

This article describes the preparation and optimization of biotin-polyethyl eneglycol (PEG) liposomes and their application in experimental infection m odels to improve the scintigraphic imaging of infection and inflammation. M ethods: Biotin was coupled to PEG-distearoylphosphatidylethanolamine (DSPE) and subsequently incorporated in the PEG liposomes. Biotinylated liposomes were radiolabeled with Tc-99m-hydrazinonicotinamide. In vitro binding stud ies were performed to find the optimal biotin concentration in the liposome s. In rats the biodistribution of the Tc-99m-biotin-PEG liposomes was compa red with the biodistribution of normal (nonbiotinylated) Tc-99m-PEG liposom es. Furthermore, in vivo studies in rats were performed to study both the e ffect of the biotin content and the optimal avidin dose for efficient clear ance 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 c alf muscle. Avidin was injected 4 h after injection of the liposomes. Resul ts: Biotinylation of the liposomes did not affect their in vivo behavior. A ll biotin-PEG liposome formulations tested showed good in vitro avidin bind ing with 50% inhibitory concentrations ranging from 36 to 8 mu mol/L. With avidin doses higher than 100 mu g, both preparations rapidly cleared from t he circulation. As a result, abscess-to-blood ratios increased Ei-fold. To illustrate the potential of the avidin-induced clearance of radiolabeled PE G liposomes, we also studied the Tc-99m-biotin-PEG liposomes in rabbits wit h a subcutaneous S. aureus abscess. The infection was visualized only after injection of 100 mu g avidin. Conclusion: This study shows that biotin-coa ted Tc-99m-PEG liposomes in combination with the injection of avidin can le ad to improved imaging of infection or inflammation localized especially in regions with high blood-pool activity.