A convenient and reproducible method for the synthesis of astatinated 4-[<sup>211</sup>At]astato-<scp>l</scp>-phenylalanine<i>via</i>electrophilic desilylation

Watanabe, Shigeki; Azim, Mohammad Anwar-Ul; Nishinaka, I.; Sasaki, Iwao; Ohshima, Yasuhiro; Yamada, Keiichi; Ishioka, Noriko S.

doi:10.1039/c8ob02394h

Cited by 20 publications

(14 citation statements)

References 33 publications

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“…In addition, we used a borono-precursor to achieve the 211 At labeling of PA. This preparation method proceeded efficiently under mild conditions in aqueous media and did not require any toxic reagents, in contrast to previous work [12][13][14].…”

Section: Discussionmentioning

confidence: 88%

Targeted alpha therapy using astatine (211At)-labeled phenylalanine: A preclinical study in glioma bearing mice

et al. 2020

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Phenylalanine derivatives, which target tumors especially through L-type amino acid transporter-1 (LAT1), have elicited considerable attention. In this study, we evaluated the treatment effect of phenylalanine labeled with the alpha emitter astatine ( 211 At-PA) in tumor bearing mice. The C6 glioma, U-87MG, and GL261 cell lines were subjected to a cellular 211 At-PA uptake analysis that included an evaluation of the uptake inhibition by the system L amino acid transporter inhibitor 2-aminobicyclo-(2,2,1)-heptane-2-carboxylic acid (BCH). BCH significantly inhibited para-211 At-PA uptake in C6 glioma (12.2 ± 0.8%), U-87MG (27.6 ± 1.1%), and GL261 (12.6 ± 2.0%) cells compared to baseline, suggesting an uptake contribution by system L amino acid transporters. Subsequently, xenograft and allograft models were prepared by subcutaneously injecting C6 glioma (n = 12) or GL-261 cells (n = 12), respectively. C6 glioma mice received three 211 At-PA doses (0.1, 0.5, or 1 MBq, n = 3/dose), while GL261 mice received one high dose (1 MBq, n = 7). 211 At-PA exhibited a tumor growth suppression effect in C6 glioma models in a dose-dependent manner as well as in GL-261 models. This phenylalanine derivative labeled with astatine may be applicable as an alpha therapy that specifically targets system L amino acid transporters.

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Section: Discussionmentioning

confidence: 88%

Targeted alpha therapy using astatine (211At)-labeled phenylalanine: A preclinical study in glioma bearing mice

et al. 2020

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“…Although initially developed with organomercuric derivatives [ 102 ], trialkylaryltin were preferred, Sn(alkyl) 3 being good leaving groups associated to a lower toxicity [ 103 ]. Recently, silicon derivatives were proposed as possible alternative to stannylated compounds [ 104 ]. The other approach is based on the At − species, presented to be easier to handle due to a larger predominance domain than At + .…”

Section: Astatine-211mentioning

confidence: 99%

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

et al. 2021

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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.

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“…Phenylalanine has been previously labeled with 211 At using different methods 3 – 5 . However, most of these methods have certain limitations.…”

Section: Introductionmentioning

confidence: 99%

“…They also prepared [ 211 At]APA by the electrophilic destannylation of N -Boc-4-tributylstannyl-L-phenylalanine; however, the organic tin compound used in this reaction is hazardous for the environment. Watanabe et al recently reported the synthesis of [ 211 At]APA via electrophilic desilation; the corresponding 211 At-labeled triethylsilyl substituted precursor was heated at 70 ℃ for 10 min in a methanol–trifluoroacetate solvent mixture 5 . The overall radiochemical yield in this method was in the range 65–85%.…”

Section: Introductionmentioning

confidence: 99%

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Synthesis of [211At]4-astato-L-phenylalanine by dihydroxyboryl-astatine substitution reaction in aqueous solution

Shirakami

Watabe

Obata

et al. 2021

Sci Rep

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Astatine-211 (211At)-labeled phenylalanine is expected to be a promising agent for targeted alpha-particle therapy for the treatment of patients with glioma. The existing reactions to prepare the labeled compound usually require organic solvents and metals that are toxic and hazardous to the environment. In this study, we developed a novel method wherein astatination was realized via the substitution of 211At for a dihydroxyboryl group coupled to phenylalanine. [211At]4-astato-L-phenylalanine was obtained as the carrier-free product in aqueous medium in high radiochemical yields (98.1 ± 1.9%, n = 5). The crude reaction mixture was purified by solid-phase extraction, and the radiochemical purity of the product was 99.3 ± 0.7% (n = 5). The high yield and purity were attributed to the formation of [211At]AtI and AtI2− as the reactive intermediates in the astatination reaction. The reaction did not require any organic solvents or toxic reagents, suggesting that this method is suitable for clinical applications.

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A convenient and reproducible method for the synthesis of astatinated 4-[²¹¹At]astato-l-phenylalanineviaelectrophilic desilylation

Abstract: Electrophilic desilylation allows for convenient and reproducible synthesis of the aromatic amino acid derivative 4-[211At]astato-l-phenylalanine.

Cited by 20 publications

References 33 publications

Targeted alpha therapy using astatine (211At)-labeled phenylalanine: A preclinical study in glioma bearing mice

Targeted alpha therapy using astatine (211At)-labeled phenylalanine: A preclinical study in glioma bearing mice

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

Synthesis of [211At]4-astato-L-phenylalanine by dihydroxyboryl-astatine substitution reaction in aqueous solution

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A convenient and reproducible method for the synthesis of astatinated 4-[211At]astato-l-phenylalanineviaelectrophilic desilylation

Abstract: Electrophilic desilylation allows for convenient and reproducible synthesis of the aromatic amino acid derivative 4-[211At]astato-l-phenylalanine.

Cited by 20 publications

References 33 publications

Targeted alpha therapy using astatine (211At)-labeled phenylalanine: A preclinical study in glioma bearing mice

Targeted alpha therapy using astatine (211At)-labeled phenylalanine: A preclinical study in glioma bearing mice

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

Synthesis of [211At]4-astato-L-phenylalanine by dihydroxyboryl-astatine substitution reaction in aqueous solution

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A convenient and reproducible method for the synthesis of astatinated 4-[²¹¹At]astato-l-phenylalanineviaelectrophilic desilylation