title: Investigation of the chick embryo as a potential alternative to the mouse for evaluation of radiopharmaceuticals.
abstract: BACKGROUND
  The chick embryo is an emerging in vivo model in several areas of pre-clinical research including radiopharmaceutical sciences. Herein, it was evaluated as a potential test system for assessing the biodistribution and in vivo stability of radiopharmaceuticals. For this purpose, a number of radiopharmaceuticals labeled with (18)F, (125)I, (99m)Tc, and (177)Lu were investigated in the chick embryo and compared with the data obtained in mice.
  
  
  METHODS
  Chick embryos were cultivated ex ovo for 17-19 days before application of the radiopharmaceutical directly into the peritoneum or intravenously using a vein of the chorioallantoic membrane (CAM). At a defined time point after application of radioactivity, the embryos were euthanized by shock-freezing using liquid nitrogen. Afterwards they were separated from residual egg components for post mortem imaging purposes using positron emission tomography (PET) or single photon emission computed tomography (SPECT).
  
  
  RESULTS
  SPECT images revealed uptake of [(99m)Tc]pertechnetate and [(125)I]iodide in the thyroid of chick embryos and mice, whereas [(177)Lu]lutetium, [(18)F]fluoride and [(99m)Tc]-methylene diphosphonate ([(99m)Tc]-MDP) were accumulated in the bones. [(99m)Tc]-dimercaptosuccinic acid ((99m)Tc-DMSA) and the somatostatin analog [(177)Lu]-DOTATOC, as well as the folic acid derivative [(177)Lu]-DOTA-folate showed accumulation in the renal tissue whereas [(99m)Tc]-mebrofenin accumulated in the gall bladder and intestine of both species. In vivo dehalogenation of [(18)F]fallypride and of the folic acid derivative [(125)I]iodo-tyrosine-folate was observed in both species. In contrast, the 3'-aza-2'-[(18)F]fluorofolic acid ([(18)F]-AzaFol) was stable in the chick embryo as well as in the mouse.
  
  
  CONCLUSIONS
  Our results revealed the same tissue distribution profile and in vivo stability of radiopharmaceuticals in the chick embryo and the mouse. This observation is promising with regard to a potential use of the chick embryo as an inexpensive and simple test model for preclinical screening of novel radiopharmaceuticals.
authors.affiliation: Center for Radiopharmaceutical Sciences ETH-PSI-USZ, Paul Scherrer Institute, Villigen-PSI, Switzerland.
authors.forename: Stephanie
authors.initials: S
authors.lastname: Haller
authors.affiliation: Department of Chemistry and Applied Biosciences, ETH Zurich, Zurich, Switzerland.
authors.forename: Simon M
authors.initials: SM
authors.lastname: Ametamey
authors.affiliation: Center for Radiopharmaceutical Sciences ETH-PSI-USZ, Paul Scherrer Institute, Villigen-PSI, Switzerland; Department of Chemistry and Applied Biosciences, ETH Zurich, Zurich, Switzerland.
authors.forename: Roger
authors.initials: R
authors.lastname: Schibli
authors.affiliation: Center for Radiopharmaceutical Sciences ETH-PSI-USZ, Paul Scherrer Institute, Villigen-PSI, Switzerland. Electronic address: cristina.mueller@psi.ch.
authors.forename: Cristina
authors.initials: C
authors.lastname: Müller
mesh_terms: D000818:Animals; D001842:Bone and Bones / Q000000981:diagnostic imaging / Q000378:metabolism; D002642:Chick Embryo; D005240:Feasibility Studies; D051379:Mice; D049268:Positron-Emission Tomography; D019275:Radiopharmaceuticals / Q000493:pharmacokinetics*; D013045:Species Specificity; D013961:Thyroid Gland / Q000000981:diagnostic imaging; D014018:Tissue Distribution; D015899:Tomography, Emission-Computed, Single-Photon
chemical_list: D019275:Radiopharmaceuticals
keywords: Chick embryo; Defluorination; In vivo stability; PET; Radiopharmaceutical; SPECT