[¹⁸⁶Re]Liposomal doxorubicin (Doxil): in vitro stability, pharmacokinetics, imaging and biodistribution in a head and neck squamous cell carcinoma xenograft model

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.