Therapeutic efficacy of 188Re-liposome in a C26 murine colon carcinoma solid tumor model

Invest New Drugs. 2013 Aug;31(4):801-11. doi: 10.1007/s10637-012-9906-7. Epub 2012 Dec 9.

Abstract

Nanoliposomes are good drug delivery systems that allow the encapsulation of drugs into vesicles for their delivery. The objective of this study is to investigate the therapeutic efficacy of a new radio-therapeutics of (188)Re-labeled pegylated liposome in a C26 murine colon carcinoma solid tumor model. The safety of (188)Re-liposome was evaluated before radiotherapy treatment. The anti-tumor effect of (188)Re-liposome was assessed by tumor growth inhibition, survival ratio and ultrasound imaging. Apoptotic marker in tumor was also evaluated by the TUNEL (terminal deoxynucleotidyl transferase biotin-dUTP nick-end labeling) method after injection of (188)Re-liposome. The group treated with (188)Re-liposome displayed slight loss in body weight and decrease in white blood cell (WBC) count 7 to 14 days post-injection. With respect to therapeutic efficacy, the tumor-bearing mice treated with (188)Re-liposome showed better mean tumor growth inhibition rate (MGI) and longer median survival time (MGI = 0.140; 80 day) than those treated with anti-cancer drug 5-FU (MGI = 0.195; 69 day) and untreated control mice (MGI = 0.413; 48 day). The ultrasound imaging showed a decrease in both tumor volume and number of blood vessels. There were significantly more apoptotic nuclei (TUNEL-positive) in (188)Re-liposome-treated mice at 8 h after treatment than in control mice. These results evidenced the potential benefits achieved by oncological application of the radio-therapeutics (188)Re-liposome for adjuvant cancer treatment.

MeSH terms

  • Animals
  • Apoptosis / drug effects
  • Cell Line, Tumor
  • Cell Proliferation / drug effects
  • Colonic Neoplasms / diagnostic imaging
  • Colonic Neoplasms / drug therapy*
  • Colonic Neoplasms / pathology
  • Disease Models, Animal
  • Ethylenediamines / administration & dosage
  • Ethylenediamines / therapeutic use*
  • Ethylenediamines / toxicity
  • Fluorouracil / administration & dosage
  • Fluorouracil / pharmacology
  • Fluorouracil / therapeutic use
  • Injections, Intravenous
  • Isotope Labeling
  • Liposomes / administration & dosage
  • Liposomes / therapeutic use*
  • Liposomes / toxicity
  • Male
  • Mice
  • Mice, Inbred BALB C
  • Organometallic Compounds / administration & dosage
  • Organometallic Compounds / therapeutic use*
  • Organometallic Compounds / toxicity
  • Survival Analysis
  • Treatment Outcome
  • Ultrasonography

Substances

  • 188Re-N,N-bis(2-mercaptoethyl)-N',N'-diethylethylenediamine
  • Ethylenediamines
  • Liposomes
  • Organometallic Compounds
  • Fluorouracil