title: [(186)Re]Liposomal doxorubicin (Doxil): in vitro stability, pharmacokinetics, imaging and biodistribution in a head and neck squamous cell carcinoma xenograft model.
abstract: 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.
authors.affiliation: Department of Radiology, University of Texas Health Science Center, San Antonio, 78229-3900, USA.
authors.forename: Anuradha
authors.initials: A
authors.lastname: Soundararajan
authors.forename: Ande
authors.initials: A
authors.lastname: Bao
authors.forename: William T
authors.initials: WT
authors.lastname: Phillips
authors.forename: Ricardo
authors.initials: R
authors.lastname: Perez
authors.forename: Beth A
authors.initials: BA
authors.lastname: Goins
mesh_terms: D000818:Animals; D001345:Autoradiography; D002294:Carcinoma, Squamous Cell / Q000188:drug therapy* / Q000378:metabolism* / Q000473:pathology; D004195:Disease Models, Animal; D004317:Doxorubicin / Q000737:chemistry / Q000493:pharmacokinetics* / Q000627:therapeutic use; D004355:Drug Stability; D005240:Feasibility Studies; D006258:Head and Neck Neoplasms / Q000188:drug therapy* / Q000378:metabolism* / Q000473:pathology; D006801:Humans; D008297:Male; D011868:Radioisotopes / Q000627:therapeutic use; D051381:Rats; D012211:Rhenium / Q000737:chemistry* / Q000627:therapeutic use; D013194:Staining and Labeling; D014018:Tissue Distribution; D015899:Tomography, Emission-Computed, Single-Photon; D014057:Tomography, X-Ray Computed; D014183:Transplantation, Heterologous
chemical_list: D011868:Radioisotopes; D012211:Rhenium; D004317:Doxorubicin