A practical synthesis of [18F]FtRGD: An angiogenesis biomarker for PET

Romain Bejot, Julian Goggi, Shebbrin S. Moonshi, Edward G. Robins

Research output: Contribution to journalArticlepeer-review

11 Citations (Scopus)

Abstract

Integrins have become increasingly attractive targets for molecular imaging of angiogenesis with positron emission tomography or single-photon emission computed tomography, but the reliable production of radiopharmaceuticals remains challenging. A strategy for chemoselective labeling of the integrin ligand - c(RGDyK) peptide - has been developed on the basis of the Cu(I)-catalyzed conjugation reaction. Recently, we reported a nucleophilic detagging and fluorous solid-phase extraction method providing an easy way to implement an approach for obtaining 2-[18F]fluoroethyl azide. In this work, we report the practical use of this method for the preparation of the 2-[ 18F]fluoroethyl-triazolyl conjugated c(RGDyK) peptide: [ 18F]FtRGD. The two-step, two-pot synthesis, HPLC purification, and reformulation could be readily performed with a standard nucleophilic radiofluorination synthesizer (GE TRACERlab FXFN), with minimal modifications. [18F]FtRGD was obtained in a solution for injection (>500 MBq/mL) in 10-30% nondecay-corrected radiochemical yield, excellent radiochemical purity (>98%), and 28 ± 13 GBq/μmol specific activity. [18F]FtRGD (Ki = 54 ± 14 nM for αVβ3 and 1.7 ± 0.2 nM for αVβ5) was evaluated in mice and showed good stability in vivo, good tumor-to-background ratio (1.6 ± 0.3 %ID/g at 1.5 h post-injection in U87-MG tumors), and rapid urinary excretion. Therefore, [18F]FtRGD proved valuable for preclinical positron emission tomography imaging of integrin expression. A two-step, two-pot, and chemoselective strategy was developed for the radiolabeling of the c(RGDyK) peptide. Via nucleophilic detagging and fluorous solid-phase extraction, we obtain 2-[18F]fluoroethyl azide that is further used in the CuAAC conjugation reaction to prepare the 2-[18F]fluoroethyl-triazolyl conjugated c(RGDyK) peptide: [18F]FtRGD. [18F]FtRGD displayed a good affinity and selectivity for integrins both in vitro and in vivo, and proved valuable for preclinical positron emission tomography imaging of integrin expression.

Original languageEnglish
Pages (from-to)42-49
Number of pages8
JournalJournal of Labelled Compounds and Radiopharmaceuticals
Volume56
Issue number2
DOIs
Publication statusPublished or Issued - Feb 2013
Externally publishedYes

Keywords

  • CuAAC
  • F-18
  • PET
  • RGD
  • angiogenesis
  • fluorous
  • integrins

ASJC Scopus subject areas

  • Analytical Chemistry
  • Biochemistry
  • Radiology Nuclear Medicine and imaging
  • Drug Discovery
  • Spectroscopy
  • Organic Chemistry

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