Chemoradionuclide therapy with 186Re-labeled liposomal doxorubicin: Toxicity, dosimetry, and therapeutic response

Anuradha Soundararajan, Ande Bao, William T. Phillips, Linda M. McManus, Beth A. Goins

Research output: Contribution to journalArticle

11 Scopus citations

Abstract

This study was performed to determine the maximum tolerated dose (MTD) and therapeutic effects of rhenium-186 (186Re)-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 186Re-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 186Re-Doxil (185-925 MBq/kg) or 186Re-PEG-liposomes (1110-1665 MBq/kg) and were monitored for 28 days. Based on body weight loss and systemic toxicity, MTD for 186Re-Doxil and 186Re-PEG- liposomes were established at injected radioactivity/body weight of 740 and 1480 MBq/kg, respectively. 186Re-injected radioactivity/body weight for therapy studies was determined to be 555 MBq/kg for 186Re-Doxil and 1295 MBq/kg for 186Re-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 186Re-Doxil (0.299±0.109 Gy/MBq) compared with 186Re-PEG-liposomes (0.096±0.120 Gy/MBq) (p<0.05). In a separate therapy study, tumor volumes were significantly smaller for 186Re-Doxil (555 MBq/kg) compared with 186Re-PEG-liposomes (1295 MBq/kg) (p<0.01) at 42 days postinjection. In conclusion, combination chemoradionuclide therapy with 186Re-Doxil has promising potential, because good tumor control was achieved with limited associated toxicity.

Original languageEnglish (US)
Pages (from-to)603-614
Number of pages12
JournalCancer Biotherapy and Radiopharmaceuticals
Volume26
Issue number5
DOIs
StatePublished - Oct 1 2011

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Keywords

  • MTD
  • Re
  • head and neck cancer
  • imaging
  • liposomal doxorubicin
  • radionuclide therapy

ASJC Scopus subject areas

  • Oncology
  • Radiology Nuclear Medicine and imaging
  • Pharmacology
  • Cancer Research

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