A novel method to label liposomes with Tc-99m by the hydrazino nicotinyl derivative

In this study a new Tc-99m labeling method for polyethyleneglycol (PEG)-coa ted liposomes is described. The in vitro and in vivo characteristics were c ompared with the conventional Tc-99m-HMPAO-labeled PEG-coated liposomes. Me thods: PEG-coated liposomes were labeled with Tc-99m by the hydrazino nicot inyl (HYNIC) derivative of distearoylphosphatidyl-ethanolamine (DSPE) and c ompared with PEG-coated liposomes labeled with Tc-99m-HMPAO. in vitro stabi lity tests were performed. Biodistribution and imaging characteristics of b oth liposomal preparations were determined in rats with Staphylococcus aure us infection in the left calf muscle. Results: Per liposome, 230 hydrazine groups were incorporated. The labeling efficiency of the Tc-99m-HYNIC lipos omes was greater than 95%, so no postlabeling purification was required, in contrast to the 99mTc-HMPAO liposomes. The Tc-99m-HYNIC liposomes showed g reater in vitro stability than the conventional 99mTc-HMPAO liposomes. Absc ess uptake of the Tc-99m-HYNIC liposomes was significantly greater (1.74 +/ - 0.38%ID/g versus 1.26 +/- 0.29%ID/g, 24 h postinjection, P < 0.03). Furth ermore, kidney uptake of the Tc-99m-HYNIC liposomes was one third of the up take of the Tc-99m-HMPAO liposomes (0.79 +/- 0.07ID/g versus 2.47 +/- 0.35% ID/g, 24 h postinjection, P < 0.0001). Conclusion: This new Tc-99m-HYNIC-ba sed labeling method for liposomes is rapid, efficient and easy to perform. Most importantly, the Tc-99m-labeled liposomes have an improved stability a nd in vivo characteristics. The new labeling method is a major step forward toward a radiopharmaceutical for infection imaging that can be prepared in a one-step procedure within 15 min at room temperature and thus can be app lied in every routine clinical practice.