73538-17-7

Upstream product

• 62561-75-5 (R)-2-amino-3-(4-iodophenyl)propanoic acid 
• 1991-81-7 4-iodo-L-phenylalanine 
• 76410-58-7 p-borono-L-phenylalanine 

Relevant academic research and scientific papers

211At and 125I-Labeling of (Hetero)Aryliodonium Ylides: Astatine Wins Again

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.

METHODS OF TREATMENT

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.

PRODUCTION METHOD FOR RADIOLABELED ARYL COMPOUND

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.

A convenient and reproducible method for the synthesis of astatinated 4-[211At]astato-l-phenylalanine: Via electrophilic desilylation

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.

THERAPY OF HORMONE DEPENDENT CARCINOMA AND HORMONE-REFRACTORY OR METASTASIZED CARCINOMA DERIVED FROM HORMONE DEPENDENT CARCINOMA

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