The preparation of astatine labelled tyrosine using an electrophilic reaction

Norseyev, Yu. V.; Nhan, D. D.; Khalkin, V.A.; Huan, N. Q.; Vasaros, L.

doi:10.1007/bf02167979

Cited by 9 publications

(4 citation statements)

References 3 publications

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“…Hydrogen substitution on aromatic rings has been investigated by several research groups to understand the mechanisms of introduction of astatine on protein (which differ from iodine, see next section). Thus, it was demonstrated that the astatination of tyrosine requires conditions that are denaturing for proteins (T = 160°C in the presence of an oxidizing agent), 51 highlighting the fact that direct radiolabeling of antibodies on tyrosine residues as it is performed with radioiodine is unlikely with astatine.…”

Section: The Organic Chemistry Of Astatinementioning

confidence: 98%

Production of [²¹¹At]-Astatinated Radiopharmaceuticals and Applications in Targeted α-Particle Therapy

Guérard

Gestin

Brechbiel

2013

Cancer Biotherapy and Radiopharmaceuticals

107

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(211)At is a promising radionuclide for α-particle therapy of cancers. Its physical characteristics make this radionuclide particularly interesting to consider when bound to cancer-targeting biomolecules for the treatment of microscopic tumors. (211)At is produced by cyclotron irradiation of (209)Bi with α-particles accelerated at ~28 MeV and can be obtained in high radionuclidic purity after isolation from the target. Its chemistry resembles iodine, but there is also a tendency to behave as a metalloid. However, the chemical behavior of astatine has not yet been clearly established, primarily due to the lack of any stable isotopes of this element, which precludes the use of conventional analytical techniques for its characterization. There are also only a limited number of research centers that have been able to produce this element in sufficient amounts to carry out extensive investigations. Despite these difficulties, chemical reactions typically used with iodine can be performed, and a number of biomolecules of interest have been labeled with (211)At. However, most of these compounds exhibit unacceptable instability in vivo due to the weakness of the astatine-biomolecule bond. Nonetheless, several compounds have shown high potential for the treatment of cancers in vitro and in several animal models, thus providing a promising basis that has allowed initiation of the first two clinical studies.

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Section: The Organic Chemistry Of Astatinementioning

confidence: 98%

Production of [²¹¹At]-Astatinated Radiopharmaceuticals and Applications in Targeted α-Particle Therapy

Guérard

Gestin

Brechbiel

2013

Cancer Biotherapy and Radiopharmaceuticals

107

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“…Initially, the instability was ascribed to the vulnerability of the At–C [ 52 ] or At–S bond (this kind of bonding is easily hydrolyzed in vivo) [ 53 ], assuming that astatine reacted with the tyrosine, histidine, or cysteine residues of the proteins when employing the direct radiolabeling method. Norseyev Y et al [ 54 ] completed the carrier-free astatotyrosine using an electrophilic reaction in acidic media, and the yield was about 90%. The optimal conditions of a temperature range of 150–160 °C and reaction time of 20–30 min were chosen for synthesizing astatotyrosine that was denaturing for proteins, which means it was performed with radioiodine and was unlikely with astatine.…”

Section: Electrophilic Substitutionmentioning

confidence: 99%

The Different Strategies for the Radiolabeling of [211At]-Astatinated Radiopharmaceuticals

Gao,

Li,

Yin

et al. 2024

Pharmaceutics

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Astatine-211 (211At) has emerged as a promising radionuclide for targeted alpha therapy of cancer by virtue of its favorable nuclear properties. However, the limited in vivo stability of 211At-labeled radiopharmaceuticals remains a major challenge. This review provides a comprehensive overview of the current strategies for 211At radiolabeling, including nucleophilic and electrophilic substitution reactions, as well as the recent advances in the development of novel bifunctional coupling agents and labeling approaches to enhance the stability of 211At-labeled compounds. The preclinical and clinical applications of 211At-labeled radiopharmaceuticals, including small molecules, peptides, and antibodies, are also discussed. Looking forward, the identification of new molecular targets, the optimization of 211At production and quality control methods, and the continued evaluation of 211At-labeled radiopharmaceuticals in preclinical and clinical settings will be the key to realizing the full potential of 211At-based targeted alpha therapy. With the growing interest and investment in this field, 211At-labeled radiopharmaceuticals are poised to play an increasingly important role in future cancer treatment.

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“…In the early stages of development, aromatic astato compounds were synthesized by exchange halogenation [41-45] or by electrophilic substitution on unactivated [46] or activated aromatic rings [38, 47, 48]. Recently, a commonly used method for exchange radioiodination using copper catalysts has been adapted for astatination [49].…”

Section: Astatine-211mentioning

confidence: 99%

Astatine Radiopharmaceuticals: Prospects and Problems

Vaidyanathan¹,

Zalutsky²

2008

CRP

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For the treatment of minimum residual diseases such micrometastases and residual tumor margins that remain after debulking of the primary tumor, targeted radiotherapy using radiopharmaceuticals tagged with α-particle-emitting radionuclides is very attractive. In addition to the their short range in tissue, which helps minimize harmful effects on adjacent normal tissues, α-particles, being high LET radiation, have several radiobiological advantages. The heavy halogen, astatine-211 is one of the prominent α-particle-emitting radionuclides in practice. Being a halogen, it can often be incorporated into biomolecules of interest by adapting radioiodination chemistry. A wide spectrum of compounds from the simple [ 211 At]astatide ion to small organic molecules, peptides, and large proteins labeled with 211 At have been investigated with at least two reaching the stage of clinical evaluation. The chemistry, cytotoxic advantages, biodistribution studies, and microdosimetry/ pharmacokinetic modeling of some of these agents will be reviewed. In addition, potential problems such as the harmful effect of radiolysis on the synthesis, lack of sufficient in vivo stability of astatinated compounds, and possible adverse effects when they are systemically administered will be discussed.

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The preparation of astatine labelled tyrosine using an electrophilic reaction

Cited by 9 publications

References 3 publications

Production of [²¹¹At]-Astatinated Radiopharmaceuticals and Applications in Targeted α-Particle Therapy

Production of [²¹¹At]-Astatinated Radiopharmaceuticals and Applications in Targeted α-Particle Therapy

The Different Strategies for the Radiolabeling of [211At]-Astatinated Radiopharmaceuticals

Astatine Radiopharmaceuticals: Prospects and Problems

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The preparation of astatine labelled tyrosine using an electrophilic reaction

Cited by 9 publications

References 3 publications

Production of [211At]-Astatinated Radiopharmaceuticals and Applications in Targeted α-Particle Therapy

Production of [211At]-Astatinated Radiopharmaceuticals and Applications in Targeted α-Particle Therapy

The Different Strategies for the Radiolabeling of [211At]-Astatinated Radiopharmaceuticals

Astatine Radiopharmaceuticals: Prospects and Problems

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Product

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Production of [²¹¹At]-Astatinated Radiopharmaceuticals and Applications in Targeted α-Particle Therapy

Production of [²¹¹At]-Astatinated Radiopharmaceuticals and Applications in Targeted α-Particle Therapy