title: Site-specific 68Ga-labeled Annexin A5 as a PET imaging agent for apoptosis.
abstract: OBJECTIVE
  Two variants of Annexin A5 (Cys2-AnxA5 and Cys165-AnxA5) were labelled with Gallium-68 in order to evaluate their biological properties.
  
  
  METHODS
  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.
  
  
  CONCLUSIONS
  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.
authors.affiliation: Radiopharmacy, KULeuven, Belgium. matthias.bauwens@pharm.kuleuven.be
authors.forename: Matthias
authors.initials: M
authors.lastname: Bauwens
authors.forename: Marijke
authors.initials: M
authors.lastname: De Saint-Hubert
authors.forename: Ellen
authors.initials: E
authors.lastname: Devos
authors.forename: Niko
authors.initials: N
authors.lastname: Deckers
authors.forename: Chris
authors.initials: C
authors.lastname: Reutelingsperger
authors.forename: Luc
authors.initials: L
authors.lastname: Mortelmans
authors.forename: Uwe
authors.initials: U
authors.lastname: Himmelreich
authors.forename: Felix M
authors.initials: FM
authors.lastname: Mottaghy
authors.forename: Alfons
authors.initials: A
authors.lastname: Verbruggen
mesh_terms: D000818:Animals; D017304:Annexin A5 / Q000737:chemistry / Q000378:metabolism / Q000493:pharmacokinetics; D000911:Antibodies, Monoclonal / Q000276:immunology / Q000494:pharmacology; D017209:Apoptosis / Q000187:drug effects / Q000528:radiation effects; D001665:Binding Sites; D001692:Biological Transport / Q000187:drug effects; D005710:Gallium Radioisotopes; D006573:Heterocyclic Compounds, 1-Ring / Q000737:chemistry; D006801:Humans; D007553:Isotope Labeling; D019169:Jurkat Cells; D008301:Maleimides / Q000737:chemistry; D051379:Mice; D010718:Phosphatidylserines / Q000378:metabolism; D049268:Positron-Emission Tomography / Q000379:methods*; D013379:Substrate Specificity; D019014:fas Receptor / Q000276:immunology
chemical_list: D017304:Annexin A5; D000911:Antibodies, Monoclonal; D005710:Gallium Radioisotopes; D006573:Heterocyclic Compounds, 1-Ring; D008301:Maleimides; D010718:Phosphatidylserines; D019014:fas Receptor; C071349:1,4,7,10-tetraazacyclododecane- 1,4,7,10-tetraacetic acid; C043592:maleimide