title: Chemoradionuclide therapy with 186re-labeled liposomal doxorubicin: toxicity, dosimetry, and therapeutic response.
abstract: This study was performed to determine the maximum tolerated dose (MTD) and therapeutic effects of rhenium-186 ((186)Re)-labeled liposomal doxorubicin (Doxil), investigate associated toxicities, and calculate radiation absorbed dose in head and neck tumor xenografts and normal organs. Doxil and control polyethylene glycol (PEG)-liposomes were labeled using (186)Re-N,N-bis(2-mercaptoethyl)-N',N'-diethylethylenediamine (BMEDA) method. Tumor-bearing rats received either no therapy (n=6), intravenous Doxil (n=4), or escalating radioactivity of (186)Re-Doxil (185-925 MBq/kg) or (186)Re-PEG-liposomes (1110-1665 MBq/kg) and were monitored for 28 days. Based on body weight loss and systemic toxicity, MTD for (186)Re-Doxil and (186)Re-PEG-liposomes were established at injected radioactivity/body weight of 740 and 1480 MBq/kg, respectively. (186)Re-injected radioactivity/body weight for therapy studies was determined to be 555 MBq/kg for (186)Re-Doxil and 1295 MBq/kg for (186)Re-PEG-liposomes. All groups recovered from their body weight loss, leucopenia, and thrombocytopenia by 28 days postinjection. Normalized radiation absorbed dose to tumor was significantly higher for (186)Re-Doxil (0.299±0.109 Gy/MBq) compared with (186)Re-PEG-liposomes (0.096±0.120 Gy/MBq) (p<0.05). In a separate therapy study, tumor volumes were significantly smaller for (186)Re-Doxil (555 MBq/kg) compared with (186)Re-PEG-liposomes (1295 MBq/kg) (p<0.01) at 42 days postinjection. In conclusion, combination chemoradionuclide therapy with (186)Re-Doxil has promising potential, because good tumor control was achieved with limited associated toxicity.
authors.affiliation: Department of Radiology, University of Texas Health Science Center at San Antonio, 7703 Floyd Curl Drive, San Antonio, TX 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: Linda M
authors.initials: LM
authors.lastname: McManus
authors.forename: Beth A
authors.initials: BA
authors.lastname: Goins
mesh_terms: D000818:Animals; D002294:Carcinoma, Squamous Cell / Q000188:drug therapy* / Q000532:radiotherapy*; D003131:Combined Modality Therapy; D004195:Disease Models, Animal; D004317:Doxorubicin / Q000494:pharmacology* / Q000633:toxicity; D006258:Head and Neck Neoplasms / Q000188:drug therapy* / Q000532:radiotherapy*; D006801:Humans; D008297:Male; D011868:Radioisotopes / Q000494:pharmacology* / Q000633:toxicity; D011874:Radiometry; D019275:Radiopharmaceuticals / Q000494:pharmacology* / Q000633:toxicity; D051381:Rats; D011923:Rats, Nude; D012211:Rhenium / Q000494:pharmacology* / Q000633:toxicity; D023041:Xenograft Model Antitumor Assays
chemical_list: D011868:Radioisotopes; D019275:Radiopharmaceuticals; D012211:Rhenium; D004317:Doxorubicin