Correlation between radioactivity and chemotherapeutics of the (111)In-VNB-liposome in pharmacokinetics and biodistribution in rats

Int J Nanomedicine. 2012;7:683-92. doi: 10.2147/IJN.S28279. Epub 2012 Feb 9.

Abstract

Background: The combination of a radioisotope with a chemotherapeutic agent in a liposomal carrier (ie, Indium-111-labeled polyethylene glycol pegylated liposomal vinorelbine, [(111)In-VNB-liposome]) has been reported to show better therapeutic efficiency in tumor growth suppression. Nevertheless, the challenge remains as to whether this therapeutic effect is attributable to the combination of a radioisotope with chemotherapeutics. The goal of this study was to investigate the pharmacokinetics, biodistribution, and correlation of Indium-111 radioactivity and vinorelbine concentration in the (111)In-VNB-liposome.

Methods: The VNB-liposome and (111)In-VNB-liposome were administered to rats. Blood, liver, and spleen tissue were collected to determine the distribution profile of the (111)In-VNB-liposome. A liquid chromatography tandem mass spectrometry system and gamma counter were used to analyze the concentration of vinorelbine and radioactivity of Indium-111.

Results: High uptake of the (111)In-VNB-liposome in the liver and spleen demonstrated the properties of a nanosized drug delivery system. Linear regression showed a good correlation (r = 0.97) between Indium-111 radioactivity and vinorelbine concentration in the plasma of rats administered the (111)In-VNB-liposome.

Conclusion: A significant positive correlation between the pharmacokinetics and biodistribution of (111)Indium radioactivity and vinorelbine in blood, spleen, and liver was found following administration of the (111)In-VNB-liposome. The liposome efficiently encapsulated both vinorelbine and Indium-111, and showed a similar concentration-radioactivity time profile, indicating the correlation between chemotherapy and radiotherapy could be identical in the liposomal formulation.

Keywords: Indium-111; liposome; pharmacokinetics; radiochemotherapy; vinorelbine.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Indium Radioisotopes / blood
  • Indium Radioisotopes / pharmacokinetics*
  • Indium Radioisotopes / pharmacology*
  • Linear Models
  • Liposomes / pharmacokinetics*
  • Liver / chemistry
  • Male
  • Radioactive Tracers
  • Rats
  • Rats, Sprague-Dawley
  • Reproducibility of Results
  • Spleen / chemistry
  • Tissue Distribution
  • Vinblastine / analogs & derivatives*
  • Vinblastine / blood
  • Vinblastine / pharmacokinetics
  • Vinblastine / pharmacology
  • Vinorelbine

Substances

  • Indium Radioisotopes
  • Liposomes
  • Radioactive Tracers
  • Vinblastine
  • Vinorelbine