First in vivo evaluation of liposome-encapsulated 223Ra as a potential alpha-particle-emitting cancer therapeutic agent

Anticancer Res. 2006 Jul-Aug;26(4B):2841-8.

Abstract

Background: Liposomes carrying chemotherapeutics have had some success in cancer treatment and may also be suitable carriers for therapeutic radionuclides. This study was designed to evaluate the biodistribution and to estimate the radiation doses of the alpha emitter 223Ra loaded into pegylated liposomes in selected tissues.

Materials and methods: 223Ra was encapsulated in pegylated liposomal doxorubicin (PLD) by ionophore-mediated loading. The biodistribution of liposomal 223Ra was compared to free cationic 223Ra in Balb/C mice.

Results: Liposomal 223Ra circulated in the blood with an initial half-life in excess of 24 hours, which agreed well with that reported for PLD in rodents, while the blood half-life of cationic 223Ra was considerably less than an hour. When liposomal 223Ra was catabolized, the released 223Ra was either excreted or taken up in the skeleton. This skeletal uptake increased up to 14 days after treatment, but did not reach the level seen with free 223Ra. Pre-treatment with non-radioactive PLD 4 days in advance lessened the liver uptake of liposomal 223Ra. Dose estimates showed that the spleen, followed by bone surfaces, received the highest absorbed doses.

Conclusion: Liposomal 223Ra was relatively stable in vivo and may have potential for radionuclide therapy and combination therapy with chemotherapeutic agents.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Alpha Particles / therapeutic use*
  • Animals
  • Doxorubicin / administration & dosage
  • Doxorubicin / analogs & derivatives*
  • Doxorubicin / blood
  • Doxorubicin / chemistry
  • Doxorubicin / pharmacokinetics
  • Female
  • Half-Life
  • Male
  • Mice
  • Mice, Inbred BALB C
  • Polyethylene Glycols / administration & dosage*
  • Polyethylene Glycols / chemistry
  • Polyethylene Glycols / pharmacokinetics
  • Radium / administration & dosage*
  • Radium / blood
  • Radium / chemistry
  • Radium / pharmacokinetics
  • Tissue Distribution

Substances

  • liposomal doxorubicin
  • Polyethylene Glycols
  • Doxorubicin
  • Radium