A novel method to label liposomes with 99mTc by the hydrazino nicotinyl derivative

In this study a new 99mTc labeling method for polyethyleneglycol (PEG)-coated liposomes is described. The in vitro and in vivo characteristics were compared with the conventional 99mTc-HMPAO-labeled PEG-coated liposomes.

PEG-coated liposomes were labeled with 99mTc by the hydrazino nicotinyl (HYNIC) derivative of distearoylphosphatidyl-ethanolamine (DSPE) and compared with PEG-coated liposomes labeled with 99mTc-HMPAO. In vitro stability tests were performed. Biodistribution and imaging characteristics of both liposomal preparations were determined in rats with Staphylococcus aureus infection in the left calf muscle.

Per liposome, 230 hydrazine groups were incorporated. The labeling efficiency of the 99mTc-HYNIC liposomes was greater than 95%, so no postlabeling purification was required, in contrast to the 99mTc-HMPAO liposomes. The 99mTc-HYNIC liposomes showed greater in vitro stability than the conventional 99mTc-HMPAO liposomes. Abscess uptake of the 99mTc-HYNIC liposomes was significantly greater (1.74+/-0.38%ID/g versus 1.26+/-0.29%ID/g, 24 h postinjection, P < 0.03). Furthermore, kidney uptake of the 99mTc-HYNIC liposomes was one third of the uptake of the 99mTc-HMPAO liposomes (0.79+/-0.07%ID/g versus 2.47+/-0.35%ID/g, 24 h postinjection, P < 0.0001).

This new 99mTc-HYNIC-based labeling method for liposomes is rapid, efficient and easy to perform. Most importantly, the 99mTc-labeled liposomes have an improved stability and 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 applied in every routine clinical practice.