Realizing Clinical Trials with Astatine-211: The Chemistry Infrastructure

Despite the consensus around the clinical potential of the α-emitting radionuclide astatine-211 ((211)At), there are only a limited number of research facilities that work with this nuclide. There are three main reasons for this: (1) Scarce availability of the nuclide. Despite a relatively large number of globally existing cyclotrons capable of producing (211)At, few cyclotron facilities produce the nuclide on a regular basis. (2) Lack of a chemical infrastructure, that is, isolation of (211)At from irradiated targets and the subsequent synthesis of an astatinated product. At present, the research groups that work with (211)At depend on custom systems for recovering (211)At from the irradiated targets. Setting up and implementing such custom units require long lead times to provide a proper working system. (3) The chemistry of (211)At. Compared with radiometals there are no well-established and generally accepted synthesis methods for forming sufficiently stable bonds between (211)At and the tumor-specific vector to allow for systemic applications. Herein we present an overview of the infrastructure of producing (211)At radiopharmaceuticals, from target to radiolabeled product including chemical strategies to overcome hurdles for advancement into clinical trials with (211)At.