Investigation of the chick embryo as a potential alternative to the mouse for evaluation of radiopharmaceuticals

Introduction: 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 F-18, I-125, Tc-99m, and Lu-177 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 [Tc-99m]pertechnetate and [I-125]iodide in the thyroid of chick embryos and mice, whereas [Lu-177]lutetium, [F-18]fluoride and [Tc-99m]-methylene diphosphonate ([Tc-99m]-MDP) were accumulated in the bones. [Tc-99m]-dimercaptosuccinic acid (Tc-99m-DMSA) and the somatostatin analog [Lu-177]-DOTATOC, as well as the folic acid derivative [Lu-177]-DOTA-folate showed accumulation in the renal tissue whereas [Tc-99m]-mebrofenin accumulated in the gall bladder and intestine of both species. In vivo dehalogenation of [F-18]fallypride and of the folic acid derivative [I-125]iodo-tyrosine-folate was observed in both species. In contrast, the 3'-aza-2'-[F-18]fluorofolic acid ([F-18]-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. (C) 2014 Elsevier Inc. All rights reserved.