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Microwave-assisted One-pot Synthesis of N-succinimidyl-4-[18F]fluorobenzoate [18F]SFB
Published on: June 28, 2011
Synthesis and Evaluation of Fluorinated Peptidomimetics Enabling the Development of 18F-Labeled Radioligands
Miguel A Herrera-Rueda1, Maxwell A Boateng1, Melinda Wuest1
1Department of Oncology, Cross Cancer Institute, University of Alberta, Edmonton, Alberta, T6G 1Z2, Canada.
Abstract:
The muscarinic acetylcholine receptor subtype M3 is validated as a promising target for imaging and therapy in breast cancer. Transcriptomic and proteomic profiling reveal its overexpression, particularly in triple-negative breast cancer. To overcome challenges in developing selective M3 inhibitors, fluorinated peptidomimetic compounds are designed featuring a β-alanine-glycine scaffold that mimics key M3 pharmacophore elements. These constructs show strong potential as lead structures for 18F-labeled positron emission tomography (PET) radioligands, as demonstrated with lead compound 24, exhibiting M3-selective binding (M1/M3, M2/M3, M4/M3, and M5/M3 > 45) with an IC50 value of 0.3 μM. Compound [18F]24 is prepared as the first M3-selective PET radioligand using reductive amination with 4-[18F]fluorobenzaldehyde, in a 35% decay-corrected radiochemical yield. Radioligand [18F]24 is tested for PET imaging of M3 receptors in preclinical breast cancer models.
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