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

The promising characteristics of the 7.2-h radiohalogen At-211 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 alpha-particle per decay, providing greater control over off-target effects. Unfortunately, the impact of At-211 within the targeted alpha-particle therapy domain has been constrained by its limited availability. Paradoxically, the most commonly used production method - via the Bi-209(alpha,2n)At-211 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 At-211 availability is the need for an accelerator capable of generating >= 28 MeV alpha-particles with sufficient beam intensities to make clinically relevant levels of 211At. In this review, currentmethodologies for the production and purification of At-211 - both by the direct production route noted above and via a Rn-211 generator system- will be discussed. The capabilities of cyclotrons that currently produce At-211 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 At-211 distribution to locations remote from production sites will be addressed. (C) 2021 Elsevier Inc. All rights reserved.

Automated summary

At-211 has promising characteristics for targeted alpha-particle therapy, with suitable chemical properties for labeling targeting vectors and emission of only one alpha-particle per decay. However, its impact is limited by availability constraints, despite utilizing a widely available natural material for production. The main impediment to wider availability is the need for specific accelerators capable of generating alpha-particles at clinically relevant levels.