title: Radioimmunoimaging of liver metastases with PET using a 64Cu-labeled CEA antibody in transgenic mice.
abstract: OBJECTIVE
  Colorectal cancer is one of the most common forms of cancer, and the development of novel tools for detection and efficient treatment of metastases is needed. One promising approach is the use of radiolabeled antibodies for positron emission tomography (PET) imaging and radioimmunotherapy. Since carcinoembryonic antigen (CEA) is an important target in colorectal cancer, the CEA-specific M5A antibody has been extensively studied in subcutaneous xenograft models; however, the M5A antibody has not yet been tested in advanced models of liver metastases. The aim of this study was to investigate the (64)Cu-DOTA-labeled M5A antibody using PET in mice bearing CEA-positive liver metastases.
  
  
  METHODS
  Mice were injected intrasplenically with CEA-positive C15A.3 or CEA-negative MC38 cells and underwent micro-computed tomography (micro-CT) to monitor the development of liver metastases. After metastases were detected, PET/MRI scans were performed with (64)Cu-DOTA-labeled M5A antibodies. H&E staining, immunohistology, and autoradiography were performed to confirm the micro-CT and PET/MRI findings.
  
  
  RESULTS
  PET/MRI showed that M5A uptake was highest in CEA-positive metastases. The %ID/cm(3) (16.5% ± 6.3%) was significantly increased compared to healthy liver tissue (8.6% ± 0.9%) and to CEA-negative metastases (5.5% ± 0.6%). The tumor-to-liver ratio of C15A.3 metastases and healthy liver tissue was 1.9 ± 0.7. Autoradiography and immunostaining confirmed the micro-CT and PET/MRI findings.
  
  
  CONCLUSIONS
  We show here that the (64)Cu-DOTA-labeled M5A antibody imaged by PET can detect CEA positive liver metastases and is therefore a potential tool for staging cancer, stratifying the patients or radioimmunotherapy.
authors.affiliation: Institute for Clinical Chemistry, Medical Faculty Mannheim, University of Heidelberg, Mannheim, Germany.
authors.forename: Stefanie
authors.initials: S
authors.lastname: Nittka
authors.affiliation: Department of Preclinical Imaging and Radiopharmacy, Werner Siemens Imaging Center, University of Tuebingen, Tuebingen, Germany.
authors.forename: Marcel A
authors.initials: MA
authors.lastname: Krueger
authors.affiliation: Department of Immunology, Beckman Research Institute, City of Hope, Duarte, California, United States of America.
authors.forename: John E
authors.initials: JE
authors.lastname: Shively
authors.affiliation: Department of Neuroradiology, Medical Faculty Mannheim, University of Heidelberg, Mannheim, Germany.
authors.forename: Hanne
authors.initials: H
authors.lastname: Boll
authors.affiliation: Department of Neuroradiology, Medical Faculty Mannheim, University of Heidelberg, Mannheim, Germany; Department of Diagnostic and Interventional Neuroradiology, University Hospital of the Rheinisch-Westfaehlische Technical University Aachen, Aachen, Germany.
authors.forename: Marc A
authors.initials: MA
authors.lastname: Brockmann
authors.affiliation: Department of Surgery, Medical Faculty Mannheim, University of Heidelberg, Mannheim, Germany.
authors.forename: Fabian
authors.initials: F
authors.lastname: Doyon
authors.affiliation: Department of Preclinical Imaging and Radiopharmacy, Werner Siemens Imaging Center, University of Tuebingen, Tuebingen, Germany.
authors.forename: Bernd J
authors.initials: BJ
authors.lastname: Pichler
authors.affiliation: Institute for Clinical Chemistry, Medical Faculty Mannheim, University of Heidelberg, Mannheim, Germany.
authors.forename: Michael
authors.initials: M
authors.lastname: Neumaier
mesh_terms: D000818:Animals; D000906:Antibodies / Q000737:chemistry / Q000276:immunology; D000911:Antibodies, Monoclonal / Q000737:chemistry / Q000276:immunology; D000918:Antibody Specificity / Q000276:immunology; D002272:Carcinoembryonic Antigen / Q000737:chemistry / Q000276:immunology; D045744:Cell Line, Tumor; D015179:Colorectal Neoplasms / Q000473:pathology; D003301:Copper Radioisotopes / Q000737:chemistry; D004195:Disease Models, Animal; D005260:Female; D018796:Immunoconjugates; D008113:Liver Neoplasms / Q000000981:diagnostic imaging* / Q000473:pathology / Q000556:secondary*; D008279:Magnetic Resonance Imaging; D051379:Mice; D008822:Mice, Transgenic; D049268:Positron-Emission Tomography; D016719:Radioimmunodetection / Q000379:methods; D019275:Radiopharmaceuticals; D055114:X-Ray Microtomography
chemical_list: D000906:Antibodies; D000911:Antibodies, Monoclonal; D002272:Carcinoembryonic Antigen; D003301:Copper Radioisotopes; D018796:Immunoconjugates; D019275:Radiopharmaceuticals