Synthesis of [18F]RGD-K5 by catalyzed [3 + 2] cycloaddition for imaging integrin αvβ3 expression in vivo

In the last few years click chemistry reactions, and in particular copper-catalyzed cycloadditions have been used extensively for the preparation of new bioconjugated molecules such as (18)F-radiolabeled radiopharmaceuticals for positron emission tomography (PET). This study is focused on the synthesis of the Siemens imaging biomarker [(18)F]RGD-K5. This cyclic peptide contains an amino acid sequence which is a well known binding motif for integrin αvβ3 involved in cellular adhesion to the extracellular matrix. We developed an improved "click" chemistry method using Cu(I)-Monophos as catalyst to conjugate [(18)F]fluoropentyne to the RGD-azide precursor yielding [(18)F]RGD-K5. A comparison is made with the registered Siemens method with respect to synthesis, purification and quality control. [(18)F]RGD-K5 was obtained after 75 min overall synthesis time with an overall radiochemical yield of 35% (EOB). The radiochemical purity was >98% and the specific radioactivity was 100-200 GBq/μmol at the EOS.