Production, isolation, and shipment of clinically relevant quantities of astatine-211: A simple and efficient approach to increasing supply

Lauren A McIntosh; Jonathan D Burns; Evgeny E Tereshatov; Riccardo Muzzioli; Kris Hagel; Noimat A Jinadu; Laura A McCann; Gabriela A Picayo; Federica Pisaneschi; David Piwnica-Worms; Steven J Schultz; Gabriel C Tabacaru; Austin Abbott; Brooklyn Green; Travis Hankins; Andrew Hannaman; Bryan Harvey; Kylie Lofton; Robert Rider; Maxwell Sorensen; Alexandra Tabacaru; Zachary Tobin; Sherry J Yennello

doi:10.1016/j.nucmedbio.2023.108387

Production, isolation, and shipment of clinically relevant quantities of astatine-211: A simple and efficient approach to increasing supply

Nucl Med Biol. 2023 Nov-Dec:126-127:108387. doi: 10.1016/j.nucmedbio.2023.108387. Epub 2023 Sep 21.

Authors

Lauren A McIntosh¹, Jonathan D Burns², Evgeny E Tereshatov³, Riccardo Muzzioli⁴, Kris Hagel³, Noimat A Jinadu⁵, Laura A McCann⁶, Gabriela A Picayo⁶, Federica Pisaneschi⁷, David Piwnica-Worms⁴, Steven J Schultz⁶, Gabriel C Tabacaru³, Austin Abbott⁶, Brooklyn Green⁶, Travis Hankins⁶, Andrew Hannaman⁶, Bryan Harvey⁸, Kylie Lofton⁶, Robert Rider⁶, Maxwell Sorensen⁶, Alexandra Tabacaru³, Zachary Tobin⁶, Sherry J Yennello⁶

Affiliations

¹ Cyclotron Institute, Texas A&M University, College Station, TX 77843, USA. Electronic address: lmcintosh@tamu.edu.
² Chemistry Department, The University of Alabama at Birmingham, Birmingham, AL 35924, USA. Electronic address: burnsjon@uab.edu.
³ Cyclotron Institute, Texas A&M University, College Station, TX 77843, USA.
⁴ Department of Cancer System Imaging, University of Texas MD Anderson Cancer Center, Houston, TX 77030, USA.
⁵ Chemistry Department, The University of Alabama at Birmingham, Birmingham, AL 35924, USA.
⁶ Cyclotron Institute, Texas A&M University, College Station, TX 77843, USA; Chemistry Department, Texas A&M University, College Station, TX 77843, USA.
⁷ Department of Cancer System Imaging, University of Texas MD Anderson Cancer Center, Houston, TX 77030, USA; Center for Translational Cancer Research, The Brown Foundation Institute of Molecular Medicine for the Prevention of Human Diseases (IMM) at The University of Texas Health Science Center at Houston, USA.
⁸ Cyclotron Institute, Texas A&M University, College Station, TX 77843, USA; Physics Department, Texas A&M University, College Station, TX 77843, USA.

PMID: 37837782
DOI: 10.1016/j.nucmedbio.2023.108387

Abstract

The alpha emitter astatine-211 (²¹¹At) is a promising candidate for cancer treatment based on Targeted Alpha (α) Therapy (TAT). A small number of facilities, distributed across the United States, are capable of accelerating α-particle beams to produce ²¹¹At. However, challenges remain regarding strategic methods for shipping ²¹¹At in a form adaptable to advanced radiochemistry reactions and other uses of the radioisotope.

Purpose: Our method allows shipment of ²¹¹At in various quantities in a form convenient for further radiochemistry.

Procedures: For this study, a 3-octanone impregnated Amberchrom CG300M resin bed in a column cartridge was used to separate ²¹¹At from the bismuth matrix on site at the production accelerator (Texas A&M) in preparation for shipping. Aliquots of 6 M HNO₃ containing up to ≈2.22 GBq of ²¹¹At from the dissolved target were successfully loaded and retained on columns. Exempt packages (<370 MBq) were shipped to a destination radiochemistry facility, University of Texas MD Anderson Cancer Center, in the form of a convenient air-dried column. Type A packages have been shipped overnight to University of Alabama at Birmingham.

Main findings: Air-dried column hold times of various lengths did not inhibit simple and efficient recovery of ²¹¹At. Solution eluted from the column was sufficiently high in specific activity to successfully radiolabel a model compound, 4-(4,4,5,5-tetramethyl-1,3,2-dioxaborolan-2-yl)aniline (1), with ²¹¹At. The method to prepare and ship ²¹¹At described in this manuscript has also been used to ship larger quantities of ²¹¹At a greater distance to University of Alabama at Birmingham.

Principal conclusions: The successful proof of this method paves the way for the distribution of ²¹¹At from Texas A&M University to research institutions and clinical oncology centers in Texas and elsewhere. Use of this simple method at other facilities has the potential increase the overall availability of ²¹¹At for preclinical and clinical studies.

Keywords: Astatine-211; Radioisotope transport; Separations chemistry.

MeSH terms

Alpha Particles / therapeutic use
Astatine* / chemistry
Astatine* / therapeutic use
Humans
Radiochemistry / methods
Radioisotopes / chemistry

Substances

Astatine-211
Astatine
Radioisotopes