Production, purification and availability of ²¹¹At: Near term steps towards global access

The promising characteristics of the 7.2-h radiohalogen ²¹¹At have long been recognized; including having chemical properties suitable for labeling targeting vectors ranging from small organic molecules to proteins, and the emission of only one α-particle per decay, providing greater control over off-target effects. Unfortunately, the impact of ²¹¹At within the targeted α-particle therapy domain has been constrained by its limited availability. Paradoxically, the most commonly used production method - via the ²⁰⁹Bi(α,2n)²¹¹At reaction - utilizes a widely available natural material (bismuth) as the target and straightforward cyclotron irradiation methodology. On the other hand, the most significant impediment to widespread ²¹¹At availability is the need for an accelerator capable of generating ≥28 MeV α-particles with sufficient beam intensities to make clinically relevant levels of ²¹¹At. In this review, current methodologies for the production and purification of ²¹¹At - both by the direct production route noted above and via a ²¹¹Rn generator system - will be discussed. The capabilities of cyclotrons that currently produce ²¹¹At will be summarized and the characteristics of other accelerators that could be utilized for this purpose will be described. Finally, the logistics of networks, both academic and commercial, for facilitating ²¹¹At distribution to locations remote from production sites will be addressed.