title: Magnetic resonance imaging of the response of a mouse model of non-small cell lung cancer to tyrosine kinase inhibitor treatment.
abstract: Mutational activation of the gene for epidermal growth factor receptor (EGFR) is 1 of the main ways by which this receptor induces non-small cell lung cancers (NSCLC). Variant III EGFR (EGFRvIII) is a potential therapeutic target in NSCLC treatment because of the high frequency of deletion mutations in this protein. This study used noninvasive magnetic resonance imaging (MRI) to investigate the role of an EGFRvIII mutant in lung tumorigenesis and tumor maintenance as well as its response to the EGFR small molecule inhibitor erlotinib (Tarceva) on bitransgenic mice. Both spin-echo and gradient-echo sequences with and without cardiac and respiratory gating were performed to image the invasive mouse lung tumor driven by EGFRvIII mutation. Tumor volumes were measured based on 2-dimensional axial MRI; 3-dimensional rendering of the images were obtained to demonstrate the spatial location and distribution of the tumor in the lung. The MRI results indicated that the tumor driven by the EGFRvIII mutation was generated and maintained in the bitransgenic mice with the use of doxycycline. Tumor monitoring via MRI showed that Erlotinib can significantly inhibit the growth of tumor in vivo. MRI has the ability to image mouse lung tumor with different sequences focusing on tissue contrasts between tumor and surroundings. The MRI approaches in this work can be applied on other antitumor drug treatment evaluation in vivo when appropriate sequences are chosen.
authors.affiliation: Department of Radiology, Brigham and Women's Hospital, Boston MA, USA. xiazhou@bwh.harvard.edu
authors.forename: Xiangzhi
authors.initials: X
authors.lastname: Zhou
authors.forename: Haihua
authors.initials: H
authors.lastname: Bao
authors.forename: Ruqayyah
authors.initials: R
authors.lastname: Al-Hashem
authors.forename: Hongbin
authors.initials: H
authors.lastname: Ji
authors.forename: Mitchell
authors.initials: M
authors.lastname: Albert
authors.forename: Kwok-Kin
authors.initials: KK
authors.lastname: Wong
authors.forename: Yanping
authors.initials: Y
authors.lastname: Sun
mesh_terms: D000818:Animals; D000970:Antineoplastic Agents / Q000627:therapeutic use*; D002289:Carcinoma, Non-Small-Cell Lung / Q000188:drug therapy*; D004318:Doxycycline / Q000627:therapeutic use; D008175:Lung Neoplasms / Q000188:drug therapy*; D008279:Magnetic Resonance Imaging; D051379:Mice; D008822:Mice, Transgenic; D047428:Protein Kinase Inhibitors / Q000627:therapeutic use*; D011505:Protein-Tyrosine Kinases / Q000037:antagonists & inhibitors*
chemical_list: D000970:Antineoplastic Agents; D047428:Protein Kinase Inhibitors; D011505:Protein-Tyrosine Kinases; D004318:Doxycycline