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 (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.