title: Orthotopic pleural mesothelioma in mice: SPECT/CT and MR imaging with HER1- and HER2-targeted radiolabeled antibodies.
abstract: OBJECTIVE
  To evaluate the potential of anti-human epidermal growth factor receptor (HER)1- and anti-HER2-targeted radiolabeled antibodies and magnetic resonance (MR) imaging for imaging of orthotopic malignant pleural mesothelioma (MPM) in mouse models.
  
  
  METHODS
  Animal studies with 165 mice were performed in accordance with National Institutes of Health guidelines for the humane use of animals, and all procedures were approved by the institutional Animal Care and Use Committee. Flow cytometry studies were performed to evaluate HER1 and HER2 expression in NCI-H226 and MSTO-211H mesothelioma cells. Biodistribution and single photon emission computed tomography (SPECT)/computed tomography (CT) imaging studies were performed in mice (four or five per group, depending on tumor growth) bearing subcutaneous and orthotopic MPM tumors by using HER1- and HER2-targeted indium 111 ((111)In)- and iodine 125 ((125)I)-labeled panitumumab and trastuzumab, respectively. Longitudinal MR imaging over 5 weeks was performed in three mice bearing orthotopic tumors to monitor tumor growth and metastases. SPECT/CT/MR imaging studies were performed at the final time point in the orthotopic models (n = 3). The standard unpaired Student t test was used to compare groups.
  
  
  RESULTS
  Orthotopic tumors and pleural effusions were clearly visualized at MR imaging 3 weeks after tumor cell inoculation. At 2 days after injection, the mean (111)In-panitumumab uptake of 29.6% injected dose (ID) per gram ± 2.2 (standard error of the mean) was significantly greater than the (111)In-trastuzumab uptake of 13.6% ID/g ± 1.0 and the (125)I-panitumumab uptake of 7.4% ID/g ± 1.2 (P = .0006 and P = .0001, respectively). MR imaging fusion with SPECT/CT provided more accurate information about (111)In-panitumumab localization in the tumor, as the tumor was poorly visualized at CT alone.
  
  
  CONCLUSIONS
  This study demonstrates the utility of radiolabeled anti-HER1 antibodies in the imaging of MPM in preclinical models.
  
  
  BACKGROUND
  http://radiology.rsna.org/lookup/suppl/doi:10.1148/radiol.12121021/-/DC1.
authors: Radioimmune & Inorganic Chemistry Section, Radiation Oncology Branch, and Molecular Imaging Program, National Cancer Institute, National Institutes of Health, 10 Center Dr, MSC 1182, Building 10, Room B3B69F, Bethesda, MD 20892, USA. tapann@gmail.com
authors: Tapan K
authors: TK
authors: Nayak
authors: Marcelino
authors: M
authors: Bernardo
authors: Diane E
authors: DE
authors: Milenic
authors: Peter L
authors: PL
authors: Choyke
authors: Martin W
authors: MW
authors: Brechbiel
mesh_terms: D000818:Animals; D000911:Antibodies, Monoclonal / Q000494:pharmacology*; D061067:Antibodies, Monoclonal, Humanized / Q000494:pharmacology; D019540:Area Under Curve; D045744:Cell Line, Tumor; D066246:ErbB Receptors / Q000378:metabolism*; D005260:Female; D005434:Flow Cytometry; D007457:Iodine Radioisotopes; D007496:Iridium Radioisotopes; D008279:Magnetic Resonance Imaging / Q000379:methods*; D008654:Mesothelioma / Q000000981:diagnostic imaging / Q000378:metabolism* / Q000473:pathology; D051379:Mice; D058990:Molecular Targeted Therapy; D064847:Multimodal Imaging / Q000379:methods*; D000077544:Panitumumab; D010996:Pleural Effusion / Q000000981:diagnostic imaging / Q000473:pathology; D049268:Positron-Emission Tomography; D018719:Erb-b2 Receptor Tyrosine Kinases / Q000378:metabolism*; D014057:Tomography, X-Ray Computed; D000068878:Trastuzumab; D051598:Whole Body Imaging; D023041:Xenograft Model Antitumor Assays
chemical_list: D000911:Antibodies, Monoclonal; D061067:Antibodies, Monoclonal, Humanized; D066246:ErbB Receptors; D007457:Iodine Radioisotopes; D007496:Iridium Radioisotopes; D000077544:Panitumumab; D018719:Erb-b2 Receptor Tyrosine Kinases; D000068878:Trastuzumab; C512478:EGFR protein, human; C508053:ERBB2 protein, human