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Review
. 2021 Jan:92:228-240.
doi: 10.1016/j.nucmedbio.2020.08.004. Epub 2020 Sep 1.

Alpha emitting nuclides for targeted therapy

Jasmine L Hatcher-Lamarre  1 , Vanessa A Sanders  1 , Mohammed Rahman  2 , Cathy S Cutler  1 , Lynn C Francesconi  3
Affiliations
Review

Alpha emitting nuclides for targeted therapy

Jasmine L Hatcher-Lamarre et al. Nucl Med Biol. 2021 Jan.

Abstract

Targeted alpha therapy (TAT) is an area of research with rapidly increasing importance as the emitted alpha particle has a significant effect on inducing cytotoxic effects on tumor cells while mitigating dose to normal tissues. Two significant isotopes of interest within the area of TAT are thorium-227 and actinium-225 due to their nuclear characteristics. Both isotopes have physical half-lives suitable for coordination with larger biomolecules, and additionally actinium-225 has potential to serve as an in vivo generator. In this review, the authors will discuss the production, purification, labeling reactions, and biological studies of actinium-225 and thorium-227 complexes and clinical studies.

Keywords: Actinium-225; Alpha therapy; Radiolabeling; Thorium-227.

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Figures

Figure 1.
Figure 1.
schematic describing the crossfire (CF) effect, radiation-induced bystander (RIBE) effect, and the abscopal (AbsE) effect (see text) this image was originally published in JNM. Haberkorn,U., Giesel, F., Morgenstern, A., Kratochwil, C The Future of Radioligand Therapy: alpha, beta or both? J Nucl Med. 2017;7:1017–1018. © SNMMI
Figure 2.
Figure 2.
Ac-225 decay chain
Figure 3.
Figure 3.
Structures of HEHA(left) and Macropa (Right)
Figure 4 (a–c).
Figure 4 (a–c).
Biodistributions of Ac[NO3], Ac[Macropa], and Ac[DOTA]
Figure 5.
Figure 5.
225Ac-IA-TLs result in BBB opening in immunocompetent mice. A. BBB opening in immunocompetent mice infused with 225Ac-IA-TLs 2 days, 5 days and 10 days post injection compared to saline infused immunocompetent mice as demonstrated by intraveneously injected Evans Blue dye. Site of intracranial injection marked by yellow arrows. B and C: Area and intensity of Evans Blue dye was found to be greater in mice that were intracranially infused with 225Ac-IA-TLs when compared with the saline control up to 10 days postinfusion.
Figure 6.
Figure 6.
Decay Scheme of Th-227.
Figure 7.
Figure 7.
The Kaplan-Meier survival plot of mice treated with 177Lu-trastuzumab and 227Th-Trastuzumab.
Figure 8.
Figure 8.
Me-2,3-HOPO
See this image and copyright information in PMC

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