The purpose of this study was to determine the feasibility of radiolabeling liposomal doxorubicin (Doxil) for cancer chemoradionuclide therapy by directly loading the therapeutic radionuclide rhenium-186 (186Re) into the liposome interior. The pharmacokinetics, imaging and biodistribution of [186Re]Doxil (555 MBq/kg) and control [186Re]polyethylene glycol (PEG) liposomes (555 MBq/kg) were determined after intravenous administration in a head and neck cancer xenograft model in nude rats. [186Re]Doxil and [186Re]PEG liposomes were radiolabeled using [186Re]N,N-bis(2-mercaptoethyl)-N′,N′-diethylethylenediamine. 186Re labeling efficiency was 76.1±8.3% with Doxil. The in vitro serum stability of [186Re]Doxil at 37°C was 38.06±12.13% at 24 h. Pharmacokinetic studies revealed that [186Re]Doxil had a two-phase blood clearance with half clearance times of 0.8 and 28.2 h. Images acquired over 120 h showed that [186Re]Doxil had slow blood clearance, low liver accumulation and increasing spleen accumulation. The biodistribution study at 120 h indicated that the percentage of injected dose (%ID) in the blood and tumor for [186Re]Doxil was 20-fold higher than that of [186Re]PEG liposomes. The %ID values in the kidney and liver were not significantly different between [186Re]Doxil and [186Re]PEG liposomes. These results suggest that the long circulation and prolonged bioavailability of [186Re]Doxil could potentially deliver high concentrations of both doxorubicin and 186Re to tumor when encapsulated in the same liposome vehicle.
ASJC Scopus subject areas
- Molecular Medicine
- Radiology Nuclear Medicine and imaging
- Cancer Research