Overview of the Most Promising Radionuclides for Targeted Alpha Therapy: The "Hopeful Eight" - PubMed (original) (raw)

Review

Overview of the Most Promising Radionuclides for Targeted Alpha Therapy: The "Hopeful Eight"

Romain Eychenne et al. Pharmaceutics. 2021.

Abstract

Among all existing radionuclides, only a few are of interest for therapeutic applications and more specifically for targeted alpha therapy (TAT). From this selection, actinium-225, astatine-211, bismuth-212, bismuth-213, lead-212, radium-223, terbium-149 and thorium-227 are considered as the most suitable. Despite common general features, they all have their own physical characteristics that make them singular and so promising for TAT. These radionuclides were largely studied over the last two decades, leading to a better knowledge of their production process and chemical behavior, allowing for an increasing number of biological evaluations. The aim of this review is to summarize the main properties of these eight chosen radionuclides. An overview from their availability to the resulting clinical studies, by way of chemical design and preclinical studies is discussed.

Keywords: actinium-225; astatine-211; bismuth-212; bismuth-213; lead-212; radium-223; targeted alpha therapy; terbium-149; thorium-227; α-emitters.

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Conflict of interest statement

The authors declare no conflict of interest.

Figures

Figure 4

Figure 4

Structures of main prosthetic groups used for 211At radiolabeling. [211At]SAB: _N_-succinimidyl-3-[211At]astatobenzoate [111,113]; [211At]SAGMB: _N_-succinimidyl 3-[211At]astato-4-guanidinomethyl benzoate [123]; B10: maleimido-_closo_-decaborate(2-) derivative [110]; MSB: _N_-2-(maleimido)ethyl-3-(trimethylstannyl)benzamide [115]; [211At]SPC: _N_-succinimidyl 5-[211At]astato-3-pyridinecarboxylate [127]; _m_-MeATE: _N_-succinimidyl-3-(trimethylstannyl)-benzoate [114]; B10-NCS: isothiocyanatophenyl-_closo_-decaborate(2-) derivative [110].

Figure 1

Figure 1

Decay schemes for the production of 225Ac and 213Bi.

Figure 2

Figure 2

Chemical structures of main 225Ac chelators.

Figure 3

Figure 3

Simplified decay scheme of 211At.

Figure 5

Figure 5

Schematic representation of 213Bi-labeled radioimmunoconjugates based on _p_-SCN-Bn-DOTA (A) or _p_-SCN-Bn-CHX-A″-DTPA (B).

Figure 6

Figure 6

Decay schemes for the production of 212Bi and 212Pb.

Figure 7

Figure 7

Schematic representation of 212Pb-labeled radioimmunoconjugates based on _p_-SCN-Bn-DOTA (A) or _p_-SCN-Bn-TCMC (B).

Figure 8

Figure 8

Decay schemes for the production of 223Ra and 227Th.

Figure 9

Figure 9

Decay scheme of 149Tb.

Figure 10

Figure 10

Schematic representation of 227Th-labeled radioimmunoconjugates based on _p_-SCN-Bn-DOTA (A) or Me-3,2-HOPO (B).

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