Molecular imaging of active mutant L858R EGF receptor (EGFR) kinase-expressing nonsmall cell lung carcinomas using PET/CT

Hsin Hsien Yeh, Kazuma Ogawa, Julius Balatoni, Uday Mukhapadhyay, Asutosh Pal, Carlos Gonzalez-Lepera, Aleksandr Shavrin, Suren Soghomonyan, Leo Flores, Daniel Young, Andrei Y. Volgin, Amer M. Najjar, Victor Krasnykh, William Tong, Mian M. Alauddin, Juri G. Gelovani

Research output: Contribution to journalArticlepeer-review

80 Scopus citations


The importance of the EGF receptor (EGFR) signaling pathway in the development and progression of nonsmall cell lung carcinomas (NSCLC) is widely recognized. Gene sequencing studies revealed that a majority of tumors responding to EGFR kinase inhibitors harbor activating mutations in the EGFR kinase domain. This underscores the need for novel biomarkers and diagnostic imaging approaches to identify patients whomay benefit fromparticular therapeutic agents and approaches with improved efficacy and safety profiles. To this goal, we developed 4-[(3-iodophenyl)amino]-7-{2-[2-{2-(2-[2-{2-([ 18F] fluoroethoxy)-ethoxy}-ethoxy]-ethoxy)-ethoxy}-ethoxy]- quinazoline-6-yl-acrylamide ([18F]F-PEG6-IPQA), a radiotracer with increased selectivity and irreversible binding to the activemutant L858R EGFR kinase. We show that PET with [18F]F-PEG6-IPQA in tumor-bearing mice discriminates H3255 NSCLC xenografts expressing L858R mutant EGFR from H441 and PC14 xenografts expressing EGFR or H1975 xenografts with L858R/T790M dual mutation in EGFR kinase domain, which confers resistance to EGFR inhibitors (i.e., gefitinib). The T790M mutation precludes the [18F]F-PEG6-IPQA from irreversible binding to EGFR. These results suggest that PET with [ 18F]F-PEG6-IPQA could be used for the selection of NSCLC patients for individualized therapy with small molecular inhibitors of EGFR kinase that are currently used in the clinic and have a similar structure (i.e., iressa, gefitinib, and erlotinib).

Original languageEnglish
Pages (from-to)1603-1608
Number of pages6
JournalProceedings of the National Academy of Sciences of the United States of America
Issue number4
StatePublished - 25 Jan 2011


  • Activation mutation
  • Epidermal growth factor receptor
  • Positron emission tomography


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