Astatine-211 based radionuclide therapy: Current clinical trial landscape

Abstract

Astatine-211 (211At) has physical properties that make it one of the top candidates for use as a radiation source for alpha particle-based radionuclide therapy, also referred to as targeted alpha therapy (TAT). Here, we summarize the main results of the completed clinical trials, further describe ongoing trials, and discuss future prospects.

211At on gold nanoparticles for targeted radionuclide therapy application

“…Trials involving human patients have been few and far between, and there is currently an effort in trying to determine the maximum tolerated dose of such treatment, as well as other side effects that could come about due to the application in patients. 46…”

Radiochemistry: A Hot Field with Opportunities for Cool Chemistry

“…Astatine-211 (α, t 1/2 = 7.21 h) has been earmarked as a highly promising radionuclide for targeted alpha therapy, with F-18 proposed as a potential diagnostic partner .…”

“…11−13 Radionuclide production is going to be critical in the coming years to ensure there is an adequate supply of both diagnostic and therapeutic radionuclides, while radiochemistry is essential for enabling the incorporation of said radionuclides into an increasingly diverse chemical space, including traditional smallmolecule pharmaceuticals, larger biologics, and nanoplatforms. There also remain questions about the right choice of theranostic pairs, including the need to label both small molecules (e.g., 18 F/ 11 C/ 211 At, 76 Br/ 77 Br, 123 I/ 124 I/ 131 I) and large peptides/biologics ( 68 Ga/ 177 Lu/ 225 Ac), as well as the need for "true" (or "matched") theranostic pairs that consist of isotopes of the same element (e.g., 61,64 Cu/ 67 Cu, 43 Sc/ 47 Sc, 86 Y/ 90 Y, 203 Pb/ 212 Pb). Development of any (or all) of these radionuclides for theranostic applications involves a complex interplay between the isotope supply, availability of appropriate radiochemistry labeling methods and/or chelation chemistry, intellectual property landscape, and regulatory pathway considerations (Figure 2).…”

211At-Labeled Nanoscale Polydopamine Decorated with FAPI for Synergistic Targeted-Alpha Therapy and Photothermal Therapy of Glioma

“…Among all the radiation emitters, 211 At has been regarded as one of the most promising medical radionuclides for endoradiotherapy. − This 100% α-emitter has a suitable half-life ( T 1/2 = 7.21 h) which fits the pharmacokinetics of many tumor targeting vehicles and allows multistep pharmaceutical synthesis. , The high linear energy transfer (LET = 98.84 keV μm –1 ) and short tissue range (50–90 μm) of alpha particles make 211 At induce effective cancer damage sparing normal organs and tissues. , Despite positive results from several clinical targeted-alpha therapy (TAT) trials, − 211 At-labeled compounds are still facing some challenges in the way to widely practical application. Currently, halodestannylation using aromatic derivatives as bifunctional coupling agents (BCAs) is still a widely used strategy to achieve 211 At radiolabeling .…”