Click chemistry provides a powerful method for selectively linking diverse molecular building blocks to create sophisticated molecules efficiently. Here, we report the use of copper(I)-catalyzed biorthogonal cycloaddition between alkynes and azides for the indirect incorporation of fluorine-18 into an estradiol-based compound, aimed at imaging estrogen receptors. The synthesis protocol was entirely established and refined using an automated module, with parameters adjusted to deliver the target molecule in satisfactory yield and avoid any solid formation. While the in vitro and in vivo data did not support advancement as a clinical radiotracer, the results are nonetheless important because automated systems are indispensable for producing PET tracers reliably and repeatedly under Good Manufacturing Practice standards, all while reducing radiation exposure to staff.
