Solving the limited availability of Astatine-211 from a European perspective: from production to the end user

Astatine-211, ²¹¹At, has long been a candidate for Targeted Alpha Therapy, TAT. However, over time, hurdles in the development of chemistry, the establishment of radiopharmacies, and the demonstration of its potential in clinical trials have been hampered by its limited availability. It is one of the rarest elements on earth and must be produced artificially. The main production route is by irradiating natural bismuth with helium ions in a cyclotron, utilizing the nuclear reaction ²⁰⁹Bi(α,2n)²¹¹At. It requires a medium-energy cyclotron capable of producing a 29 MeV α-beam. Early on, there were several such cyclotrons in Europe and worldwide, but to this day, only a few have been producing ²¹¹At. Now, many of the old cyclotrons have been decommissioned, leaving even fewer options. However, the situation is about to change with the installation of several new cyclotrons with the capacity to produce a relevant α-beam. In addition, there are also prospects evaluating the production of ²¹¹At in linear particle accelerators, LINACs, with which ²¹¹At potentially can be produced in very high amounts and high activity levels. Taking advantage of LINAC machines and new and old cyclotrons still in operation can solve the limited access to ²¹¹At today. With the production capacity in place, the astatine produced must be delivered in a relevant form to the end user. For this purpose, it also needs to meet all regulations for transporting radioactive material.

This work is the result of European Cooperation in Science and Technology, COST Action CA 19114, Network for Optimized Astatine labeled Radiopharmaceuticals, NOAR, Work Group 1 assignments, focusing on all aspects on ²¹¹At production and availability. The review addresses the progress of ²¹¹At in terms of the requirement for its targetry, production, transport and the chemical and physical form for its delivery.

With all efforts in production and making ²¹¹At available it has the potential to be the next generation Targeted Alpha Therapy radionuclide in Europe and worldwide.