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BioMed Research International
Volume 2013 (2013), Article ID 549359, 10 pages
http://dx.doi.org/10.1155/2013/549359
Research Article

Molecular Imaging of Nonsmall Cell Lung Carcinomas Expressing Active Mutant EGFR Kinase Using PET with [124I]-Morpholino-IPQA

1National PET/Cyclotron Center, Department of Nuclear Medicine, Taipei Veterans General Hospital, Taiwan
2Department of Biomedical Imaging and Radiological Sciences, National Yang-Ming University, Taipei, Taiwan
3Biophotonic and Molecular Imaging Research Center, National Yang-Ming University, Taipei, Taiwan
4Taiwan Mouse Clinic, National Comprehensive Mouse Phenotyping and Drug Testing Center, Taiwan
5Department of Experimental Diagnostic Imaging, The University of Texas MD Anderson Cancer Center, TX, USA
6Department of Medicinal Imaging and Radiological Sciences, College of Health Sciences, Kaohsiung Medical University, Kaohsiung, Taiwan
7Department of Biomedical Engineering, Wayne State University, MI, USA
8Department of Nuclear Medicine, National Yang-Ming University School of Medicine, Taiwan

Received 25 April 2013; Revised 11 June 2013; Accepted 14 June 2013

Academic Editor: Shaoli Song

Copyright © 2013 Skye Hsin-Hsien Yeh et al. This is an open access article distributed under the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited.

Abstract

Mutations in the kinase domain of epidermal growth factor receptor (EGFR) have high levels of basal receptor phosphorylation and are associated with clinical responsiveness to Iressa in patients with nonsmall cell lung cancer (NSCLC). This study aimed to assess the feasibility of morpholino-[124I]IPQA derivative as an in vivo PET imaging tool for the expression of different EGFR mutants in NSCLC. In vitro radiotracer accumulation and washout studies demonstrated a rapid accumulation and progressive retention after washout of morpholino-[131I]IPQA derivative in high EGFR-expressing H1299 NSCLC derivative cell lines (L858R and E746-A750 del cell lines), but not in EGFR-transfected H1299 cell line and vector-transfected H1299 cell line. Using the morpholino-[124I]IPQA derivative, we obtained noninvasive microPET images of EGFR activity in L858R and E746-A750 del subcutaneous tumor xenografts, but not in subcutaneous tumor xenografts grown form control cell line. Different EGFR mutant (activity) tumors have a different morpholino-[I]IPQA derivative uptake. However, it still needs to modify the structure of IPQA to increase its water solubility and reduce hepatobiliary clearance. Morpholino-[124I]IPQA derivative may be a potential probe for selection of the candidate patients suffering from NSCLC for the small molecule tyrosine kinase inhibitor therapy (e.g., Iressa) in the future.