Imaging, biodistribution and safety of Tc-99m PEG-liposomes in horses

Objectives Liposomes are phospholipid nanoparticles that extravasate at sites of increased vascular permeability. They are used for targeted drug delivery and diagnostic imaging. This study is the first to describe the i.v. administration of Tc-99m labeled polyethylene glycol (PEG)-coated liposomes in normal horses.

Methods Liposomes containing glutathione were prepared via the film hydration method and labeled using Tc-99m-HMPAO. An assay was developed to establish the 50% serum hemolytic complement activity (CH50) in horses, as complement-mediated reactions are a common adverse effect in other species. Ten horses were administered Tc-99m PEG-liposomes i.v.. Clinical parameters, hematology, plasma biochemistry and serum complement activity were monitored serially. Imaging was performed at 1, 12, and 21 h p.i.. Six horses were euthanized at 23 h and tissues of interest were dissected and uptake was calculated as %ID/kg.

Results Complement assays required the addition of C3 depleted human serum to the standard hemolytic assay to obtain a CH₅₀ value. In contrast to previous findings in humans, no significant complement activation was detected. No significant clinical changes occurred following liposome administration. Scintigraphic studies revealed a prolonged vascular phase that lasted to 21 h, with increased radiopharmaceutical uptake in the liver, lungs, spleen and kidney. There was a repeatable pattern of organ distribution similar to that seen in other species. Evaluation of tissue samples revealed greatest Tc-99m activity within the lung, kidney, liver and spleen.

Conclusions There were minimal adverse effects associated with intravenous liposome administration in normal horses. This study establishes normal scintigraphic findings after administration of Tc-99m-PEG liposomes. Liposomes have potential for diagnostic identification and targeted drug delivery in the treatment of refractory infections and neoplasia in horses