The PEGylated liposomal doxorubicin improves the delivery and therapeutic efficiency of 188Re-Liposome by modulating phagocytosis in C26 murine colon carcinoma tumor model

Nucl Med Biol. 2014 Oct;41(9):765-71. doi: 10.1016/j.nucmedbio.2014.05.142. Epub 2014 Jun 9.

Abstract

Liposome in delivering radionuclide for cancer therapy has been expansively studied; however, liposome itself can be deliberately entrapped and destroyed by the reticuloendothelial system, causing an insufficiency of the drug delivery, which in turn would restrict the effectiveness of the drug. In this study, mice with subcutaneous implantation of C26 murine colon cancer received an experimental treatment regimen in which mice took delivery of PEGylated liposomal doxorubicin (LipoDox) first, after a three-day interval, of Rhenium-188 encapsulated into PEGylated liposome ((188)Re-Liposome) subsequently and by which suppressed the functioning of reticuloendothelial system for the short term. The data showed that based upon the biodistribution assay and the evaluation of the therapeutic efficacy, (188)Re-Liposome was more sufficiently delivered to tumor sites in mice with this treatment regimen than mice without the regimen, and that cancer mortalities in mice with the treatment regimen were much lower than the mortalities in mice without the regimen. Taken together, a new strategy proposed in this study significantly improved both the (188)Re-Liposome delivery and the effectiveness of (188)Re-Liposome, suggesting that the strategy can be an ideal treatment for cancer.

Keywords: 188Re-Liposome; Bio-distribution; Colon cancer; Internal radiotherapy; Liposomal doxorubicin; Pretreatment.

MeSH terms

  • Animals
  • Cell Line, Tumor
  • Chemoradiotherapy / methods
  • Colonic Neoplasms / metabolism*
  • Colonic Neoplasms / pathology
  • Colonic Neoplasms / therapy*
  • Doxorubicin / analogs & derivatives*
  • Doxorubicin / chemistry
  • Doxorubicin / pharmacokinetics
  • Doxorubicin / therapeutic use
  • Male
  • Metabolic Clearance Rate
  • Mice
  • Mice, Inbred BALB C
  • Organ Specificity
  • Phagocytosis
  • Polyethylene Glycols / chemistry
  • Polyethylene Glycols / pharmacokinetics
  • Polyethylene Glycols / therapeutic use
  • Radioisotopes / chemistry
  • Radioisotopes / pharmacokinetics*
  • Radioisotopes / therapeutic use*
  • Rhenium / chemistry
  • Rhenium / pharmacokinetics*
  • Rhenium / therapeutic use*
  • Tissue Distribution
  • Treatment Outcome

Substances

  • Radioisotopes
  • liposomal doxorubicin
  • Polyethylene Glycols
  • Rhenium
  • Doxorubicin