Carbon-11 radiolabeling of an oligopeptide containing tryptophan hydrochloride via a Pictet-Spengler reaction using carbon-11 formaldehyde

Authors


Correspondence to: Toshimitsu Fukumura, Molecular Probe Program, Molecular Imaging Center, National Institute of Radiological Science, 4-9-1 Anagawa, Inage-ku, Chiba 263–8555, Japan. E-mail: t_fukumu@nirs.go.jp

Abstract

A procedure for the synthesis of a11C-labeled oligopeptide containing [1-11C]1,2,3,4-tetrahydro-β-carboline-3-carboxylic acid ([1-11C]Tpi) from the corresponding Trp•HCl-containing peptides has been developed involving a Pictet-Spengler reaction with [11C]formaldehyde. The synthesis of [1-11C]Tpi from Trp and [11C]formaldehyde was examined as a model reaction with the aim of developing a facile and effective method for the labeling of peptides with carbon-11. The Pictet-Spengler reaction of Trp and [11C]formaldehyde in acidic media (TsOH or HCl) afforded the desired [1-11C]Tpi in a moderate radiochemical yield. Herein, the application of a Pictet-Spengler reaction to an aqueous solution of Trp•HCl gave the desired product with a radiochemical yield of 45.2%. The RGD peptide cyclo[Arg-Gly-Asp-D-Tyr-Lys] was then selected as a substrate for the labeling reaction with [11C]formaldehyde. The radiolabeling of a Trp•HCl-containing RGD peptide using the Pictet-Spengler reaction was successful. Furthermore, the remote-controlled synthesis of a [1-11C]Tpi-containing RGD peptide was attempted by using an automatic production system to generate [11C]CH3I. The radiochemical yield of the [1-11C]Tpi-containing RGD at the end of synthesis (EOS) was 5.9 ± 1.9% (n = 4), for a total synthesis time of about 35 min. The specific activity was 85.7 ± 9.4 GBq/µmol at the EOS. Copyright © 2013 European Peptide Society and John Wiley & Sons, Ltd.

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