Due to the dependence of many cancers on the overexpression and mutation of HER2 and EGFR, the inhibition of HER2 and EGFR has been a therapeutic target of great interest.  Unfortunately, only subpopulations of patients are sensitive to anti-HER2/anti-EGFR treatments.  Consequently, efforts have been made toward using PET and SPECT to identify patients who will respond positively to anti-HER2/EGFR therapies.  Here we outline a convergent synthesis which enables incorporation of various radioisotopes into a series of tyrosine kinase inhibitors based on the common 4-anilinoquinazoline scaffold.  This approach allows for rapid diversification and optimization of potential imaging agents.  Additionally, our strategy uses extended aniline headgroups known to inhibit HER2 and the inactive conformation of EGFR. To our knowledge, this has not been done previously in the synthesis of radiolabeled imaging probes for EGFR and HER2. The authors would like to acknowledge the U.S. Department of Energy for funding this research. (DE-SC0001781).

Imaging EGFR and HER2 with small-molecule imaging agents for PET and SPECT

245th National Meeting (2013)

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