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-[F-18]fluoroethyl azide. In this work, we report the practical use of this method for the preparation of the 2-[F-18]fluoroethyl-triazolyl conjugated c(RGDyK) peptide: [F-18]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. [F-18]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/mu mol specific activity. [F-18]FtRGD (K-i = 54 +/- 14nM for alpha(V)beta(3) and 1.7 +/- 0.2nM for alpha(V)beta(5)) 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, [F-18]FtRGD proved valuable for preclinical positron emission tomography imaging of integrin expression.