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

Nucl Med Biol. 2009 Jul;36(5):515-24. doi: 10.1016/j.nucmedbio.2009.02.004. Epub 2009 May 7.


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 ((186)Re) into the liposome interior. The pharmacokinetics, imaging and biodistribution of [(186)Re]Doxil (555 MBq/kg) and control [(186)Re]polyethylene glycol (PEG) liposomes (555 MBq/kg) were determined after intravenous administration in a head and neck cancer xenograft model in nude rats. [(186)Re]Doxil and [(186)Re]PEG liposomes were radiolabeled using [(186)Re]N,N-bis(2-mercaptoethyl)-N',N'-diethylethylenediamine. (186)Re labeling efficiency was 76.1+/-8.3% with Doxil. The in vitro serum stability of [(186)Re]Doxil at 37 degrees C was 38.06+/-12.13% at 24 h. Pharmacokinetic studies revealed that [(186)Re]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 [(186)Re]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 [(186)Re]Doxil was 20-fold higher than that of [(186)Re]PEG liposomes. The %ID values in the kidney and liver were not significantly different between [(186)Re]Doxil and [(186)Re]PEG liposomes. These results suggest that the long circulation and prolonged bioavailability of [(186)Re]Doxil could potentially deliver high concentrations of both doxorubicin and (186)Re to tumor when encapsulated in the same liposome vehicle.

Publication types

  • Research Support, N.I.H., Extramural

MeSH terms

  • Animals
  • Autoradiography
  • Carcinoma, Squamous Cell / drug therapy*
  • Carcinoma, Squamous Cell / metabolism*
  • Carcinoma, Squamous Cell / pathology
  • Disease Models, Animal
  • Doxorubicin / chemistry
  • Doxorubicin / pharmacokinetics*
  • Doxorubicin / therapeutic use
  • Drug Stability
  • Feasibility Studies
  • Head and Neck Neoplasms / drug therapy*
  • Head and Neck Neoplasms / metabolism*
  • Head and Neck Neoplasms / pathology
  • Humans
  • Male
  • Radioisotopes / therapeutic use
  • Rats
  • Rhenium / chemistry*
  • Rhenium / therapeutic use
  • Staining and Labeling
  • Tissue Distribution
  • Tomography, Emission-Computed, Single-Photon
  • Tomography, X-Ray Computed
  • Transplantation, Heterologous


  • Radioisotopes
  • Rhenium
  • Doxorubicin