Site-specific 68Ga-labeled Annexin A5 as a PET imaging agent for apoptosis

Nucl Med Biol. 2011 Apr;38(3):381-92. doi: 10.1016/j.nucmedbio.2010.09.008. Epub 2010 Dec 3.

Abstract

Purpose: Two variants of Annexin A5 (Cys2-AnxA5 and Cys165-AnxA5) were labelled with Gallium-68 in order to evaluate their biological properties.

Procedures: Biodistribution and pharmacokinetics of the radiotracers were studied with μPET in healthy mice and in a mouse model of hepatic apoptosis. μPET imaging after IV injection of the tracers in combination with μMRI was performed in Daudi tumor bearing mice before and after treatment with a combination of chemotherapy and radiotherapy.

Results: The biodistribution data indicated a fast urinary clearance with only minor hepatobilliary clearance, although a high retention in the kidneys was observed. Animals treated with anti-Fas showed a 3 to 8 times higher liver uptake as compared to healthy animals. Tumor uptake of (68)Ga-Cys2-AnxA5 and (68)Ga-Cys165-AnxA5 was low but significantly increased after therapy.

Conclusion: Both (68)Ga-Cys2-AnxA5 and (68)Ga-Cys165-AnxA5 show a clear binding to apoptotic cells and are promising tracers for rapid evaluation of cancer therapy.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Annexin A5* / chemistry
  • Annexin A5* / metabolism
  • Annexin A5* / pharmacokinetics
  • Antibodies, Monoclonal / immunology
  • Antibodies, Monoclonal / pharmacology
  • Apoptosis* / drug effects
  • Apoptosis* / radiation effects
  • Binding Sites
  • Biological Transport / drug effects
  • Gallium Radioisotopes
  • Heterocyclic Compounds, 1-Ring / chemistry
  • Humans
  • Isotope Labeling
  • Jurkat Cells
  • Maleimides / chemistry
  • Mice
  • Phosphatidylserines / metabolism
  • Positron-Emission Tomography / methods*
  • Substrate Specificity
  • fas Receptor / immunology

Substances

  • Annexin A5
  • Antibodies, Monoclonal
  • Gallium Radioisotopes
  • Heterocyclic Compounds, 1-Ring
  • Maleimides
  • Phosphatidylserines
  • fas Receptor
  • 1,4,7,10-tetraazacyclododecane- 1,4,7,10-tetraacetic acid
  • maleimide