A practical synthesis of [(18) F]FtRGD: an angiogenesis biomarker for PET

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-[(18) F]fluoroethyl azide. In this work, we report the practical use of this method for the preparation of the 2-[(18) F]fluoroethyl-triazolyl conjugated c(RGDyK) peptide: [(18) F]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. [(18) F]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. [(18) F]FtRGD (Ki  = 54 ± 14 nM for αV β3 and 1.7 ± 0.2 nM for αV β5 ) 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, [(18) F]FtRGD proved valuable for preclinical positron emission tomography imaging of integrin expression.