The first design and synthesis of [11C]MKC-1 ([11C]Ro 31-7453), a new potential PET cancer imaging agent.
ABSTRACT Bisindolylmaleimide MKC-1 (formerly known as Ro 31-7453) is a novel, orally active, small-molecule, cell cycle inhibitor with broad-spectrum antitumor effects. [(11)C]MKC-1 ([(11)C]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 [(11)C]CO(2). The specific activity was 222-296 GBq/μmol at EOB and 111-148 GBq/μmol at the end of synthesis, respectively.
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ABSTRACT: Imaging protein kinase expression with radiolabeled small molecule inhibitors has been actively pursued to monitor the clinical potential of targeted therapeutics and treatments as well as to determine kinase receptor density changes related to disease progression. The goal of the present review is to provide an overview of the breadth of radiolabeled small molecules that have been synthesized to target intracellular protein kinases, not only for imaging in oncology, but also for other areas of interest, particularly the central nervous system. Considerable radiotracer development has focused on imaging receptor tyrosine kinases of growth factors, protein kinases A, B and C, and glycogen synthase kinase-3ß. Design considerations, structural attributes and relevant biological results are summarized.Molecules 01/2010; 15(11):8260-78. · 2.39 Impact Factor