Attempt to Synthesize a Quinazolinone Aryl Boronic Ester Derivative for 18F-labeling and Positron Emission Tomography Imaging of the Ghrelin Receptor
Abstract
The ghrelin receptor, crucial for regulating physiological processes and associated with various diseases, is a prime target for molecular imaging. Positron emission tomography (PET) imaging, known for its high sensitivity and non-invasive nature, has seen significant advancements. A potential PET radiotracer for the ghrelin receptor is a quinazolinone derivative with the highest reported ghrelin receptor binding affinity (IC50 = 20 pM) and favorable hydrophilicity (cLogD = 2.4). Previous attempts by Hou et al. and Childs to radiolabel this compound with fluorine-18 using nitro and spiroiodonium ylide precursors were unsuccessful. This thesis explores a novel approach using copper-mediated radiofluorination of a boronic ester precursor, though challenges arose in developing the precursor. Detailed are the issues faced during the multi-step synthesis, along with optimized reaction conditions and purification methods. This work provides guidance for future researchers in developing the PET radiotracer using copper-mediated radiofluorination and includes additional supporting data.