(18)F-Endothelin-1, a positron emission tomography (PET) radioligand for the endothelin receptor system: radiosynthesis and in vivo imaging using microPET.

Positron emission tomography (PET) is a powerful technique with the sensitivity to image and quantify receptor-bound radioligands in vivo. Recent progress in PET scanner technology has resulted in the development of dedicated tomographs designed for small animals, with resolution that allows the delineation of discrete organs and their larger substructures in rats and mice. Our aim was to determine whether endothelin-1 (ET-1) could be labelled with (18)F, and whether the resulting (18)F-ET-1 would have the required pharmacokinetic properties to permit binding and imaging of ET receptors in vivo. (18)F-ET-1 could be produced in a total radiochemical yield of 5.9+/-0.7% in 207+/-3 min (n=20). Specific radioactivities were in the range 220-370 GBq/micromol, and the radiochemical purity of the isolated (18)F-ET-1 was >95%. In vivo distribution in the rat was studied using microPET. High levels of (18)F-ET-1 uptake were found in lung and kidney, whereas liver showed moderate levels of uptake. The resolution of the microPET scanner was sufficient to differentiate heterogeneous uptake in subrenal structures in the rat.