- 211At and 125I-Labeling of (Hetero)Aryliodonium Ylides: Astatine Wins Again
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Despite the growing interest in radioiodine and 211At-labeled radiopharmaceuticals, the search for radiolabeling reactions has been somewhat neglected, resulting in a limited number of available radiosynthetic strategies. Herein we report a comparative study of nucleophilic 125I and 211At-labeling of aryliodonium ylides. Whereas radioiodination efficiency was low, 211At-labeling performed efficiently on a broad scope of precursors. The most activated aryliodonium ylides led rapidly to quantitative reactions at room temperature in acetonitrile. For deactivated precursors, heating up to 90 °C in glyme and addition of 2,2,6,6-tetramethylpiperidine-1-oxyl (TEMPO) as radical scavenger appeared essential to avoid precursor degradation and to achieve high radiochemical yields and molar activity. The approach was applied successfully to the preparation of 4-[211At]astatophenylalanine (4-APA), an amino acid derivative increasingly studied as radiotherapeutic drug for cancers. This validated aryliodonium ylides as a valuable tool for nucleophilic 211At-labeling and will complement the short but now growing list of available astatination reactions.
- Maingueneau, Clémence,Berdal, Marion,Eychenne, Romain,Gaschet, Jo?lle,Chérel, Michel,Gestin, Jean-Fran?ois,Guérard, Fran?ois
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supporting information
(2022/02/05)
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- METHODS OF TREATMENT
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The present invention is directed to methods of treating or preventing multiple myeloma in a patient in need thereof by administering 4-[211At]Astato-L-phenylalanine (4-[211At]APA) or a pharmaceutical derivative thereof to said patient.
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Page/Page column 22
(2022/02/05)
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- PRODUCTION METHOD FOR RADIOLABELED ARYL COMPOUND
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The invention relates to a method of producing the radiolabeled aryl compound (I) Ar—X, or a salt thereof, wherein X is 211At, 210At, 123I, 124I, 125I, or 131I. The method involves reacting the aryl boronic acid compound (II) Ar—Y, or a salt thereof, wherein Y is a borono group (—B(OH)2) or an ester group thereof, with a radionuclide selected from 211At, 210At, 123I, 124I, 125I and 131I, in the presence of an oxidizing agent selected from an alkali metal iodide, an alkali metal bromide, N-bromosuccinimide, N-chlorosuccinimide and hydrogen peroxide, in water.
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Paragraph 0203; 0204; 0205; 0206
(2020/12/10)
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- A convenient and reproducible method for the synthesis of astatinated 4-[211At]astato-l-phenylalanine: Via electrophilic desilylation
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The 211At-labeled compound, 4-[211At]astato-l-phenylalanine, is one of the most promising amino acid derivatives for use in targeted alpha therapy (TAT) for various cancers. Electrophilic demetallation of a stannyl precursor is the most widely used approach for labeling biomolecules with 211At. However, the low acid-resistance of the stannyl precursor necessitates the use of an N- and C-terminus-protected precursor, which results in a low overall radiochemical yield (RCY) due to the multiple synthetic steps involved. In this study, a deprotected organosilyl compound, 4-triethylsilyl-l-phenylalanine, was employed for the direct synthesis of astatinated phenylalanines. 211At was separately recovered from the irradiated 209Bi target using chloroform (CHCl3) and N-chlorosuccinimide-methanol (NCS-MeOH) solution. The RCYs of 4-[211At]astato-l-phenylalanine obtained from the triethylsilyl precursor with the use of 211At, isolated in CHCl3 and NCS-MeOH solution, were 75% and 64% respectively. In both cases, the retention time of the 4-[211At]astato-l-phenylalanine was found to be about 20 min, which showed reasonable correlation with the retention time of non-radioactive 4-halo-l-phenylalanines (4-chloro-, 4-bromo-, and 4-iodo-l-phenylalanine). The one-step reaction examined in this study involved mild reaction conditions (70 °C) and a short time (10 min) compared to the other currently reported procedures for astatination. Electrophilic desilylation was found to be very effective for the labeling of aromatic amino acids with 211At.
- Watanabe, Shigeki,Azim, Mohammad Anwar-Ul,Sasaki, Ichiro,Ohshima, Yasuhiro,Ishioka, Noriko S.,Nishinaka, Ichiro,Yamada, Keiichi
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p. 165 - 171
(2019/01/09)
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- THERAPY OF HORMONE DEPENDENT CARCINOMA AND HORMONE-REFRACTORY OR METASTASIZED CARCINOMA DERIVED FROM HORMONE DEPENDENT CARCINOMA
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The present invention provides a use of a L-phenylalanine conjugated to an alpha-, beta- or Auger-electron emitting isotope selected from the group consisting of bromine-76, bromine-77, bromine-82, iodine-124, iodine-125, iodine-131 and astatine-211 for t
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Page/Page column 22
(2008/06/13)
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