The first design and synthesis of [11C]MKC-1 ([11C]Ro 31-7453), a new potential PET cancer imaging agent

Bisindolylmaleimide MKC-1 (formerly known as Ro 31-7453) is a novel, orally active, small-molecule, cell cycle inhibitor with broad-spectrum antitumor effects. [11C]MKC-1 ([11C]Ro 31-7453) was first designed and synthesized as a new potential positron emission tomography cancer imaging agent through two different strategies. The first strategy was to prepare a carbon-11-labeled bisindolyl maleic anhydride intermediate followed by the conversion to maleimide. The second strategy involved the condensation of either carbon-11-labeled indole-3-acetamides with indole-3-glyoxalates, or indole-3-acetamides with carbon-11-labeled indole-3-glyoxalates. The radiochemical yields were 15–30%, decay corrected to end of bombardment (EOB), based on [11C]CO2. The specific activity was 222–296 GBq/μmol at EOB and 111–148 GBq/μmol at the end of synthesis, respectively.