Carbon-11 radiolabeling of an oligopeptide containing tryptophan hydrochloride via a Pictet-Spengler reaction using carbon-11 formaldehyde.
A procedure for the synthesis of a(11)C-labeled oligopeptide containing [1-(11)C]1,2,3,4-tetrahydro-β-carboline-3-carboxylic acid ([1-(11)C]Tpi) from the corresponding Trp•HCl-containing peptides has been developed involving a Pictet-Spengler reaction with [(11) C]formaldehyde. The synthesis of [1-(11)C]Tpi from Trp and [(11)C]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 [(11)C]formaldehyde in acidic media (TsOH or HCl) afforded the desired [1-(11)C]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 [(11)C]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-(11)C]Tpi-containing RGD peptide was attempted by using an automatic production system to generate [(11)C]CH3 I. The radiochemical yield of the [1-(11) C]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.
Molecular Probe Program, Molecular Imaging Center, National Institute of Radiological Science, 4-9-1 Anagawa, Inage-ku, Chiba, 263-8555, Japan.
Masayuki
M
Hanyu
Yuuki
Y
Takada
Hiroki
H
Hashimoto
Kazunori
K
Kawamura
Ming-Rong
MR
Zhang
Toshimitsu
T
Fukumura
D002243:Carbolines / Q000737:chemistry; D002250:Carbon Radioisotopes / Q000737:chemistry*; D005557:Formaldehyde / Q000737:chemistry; D006801:Humans; D057054:Molecular Imaging; D009842:Oligopeptides / Q000138:chemical synthesis* / Q000737:chemistry; D049268:Positron-Emission Tomography; D014364:Tryptophan / Q000737:chemistry*
D002243:Carbolines; D002250:Carbon Radioisotopes; D009842:Oligopeptides; D005557:Formaldehyde; C054910:1,2,3,4-tetrahydro-beta-carboline-3-carboxylic acid; D014364:Tryptophan
11C-labeled oligopeptides; Pictet-Spengler reaction; Positron emission tomography (PET); Remote-controlled synthesis; [1-11C]-1,2,3,4-Tetrahydro-β-carboline-3-carboxylic acid ([1-11C]Tpi); [11C]Formaldehyde