title: Radiolabeled cetuximab plus whole-brain irradiation (WBI) for the treatment of brain metastases from non-small cell lung cancer (NSCLC).
abstract: OBJECTIVE
  The addition of systemic drugs to whole-brain irradiation has not improved the survival of patients with multiple brain metastases, most likely because the agents did not readily cross the blood-brain barrier (BBB). Radiolabeling of cetuximab was performed to investigate whether this antibody crosses the BBB.
  
  
  METHODS
  A patient with multiple brain lesions from non-small cell lung cancer was investigated. The largest metastasis (40 x 33 x 27 mm) was selected the reference lesion. On day 1, 200 mg/m(2) cetuximab (0.25% hot and 99.75% cold antibody) were given. On day 3, 200 mg/m(2) cetuximab (cold antibody) were given. Weekly doses of 250 mg/m(2) cetuximab were administered for 3 months.
  
  
  RESULTS
  The reference lesion showed enhancement of radiolabeled cetuximab ((123)I-Erbi) on scintigraphy; (123)I-Erbi crossed the BBB and accumulated in the lesion. The reference lesion measured 31 x 22 x 21 mm at 4 months. Enhancement of contrast medium was less pronounced.
  
  
  CONCLUSIONS
  This is the first demonstration of cetuximab crossing the BBB and accumulating in brain metastasis.
authors.affiliation: Department of Radiation Oncology, University of Lübeck, Lübeck, Germany. Rades.Dirk@gmx.net
authors.forename: Dirk
authors.initials: D
authors.lastname: Rades
authors.forename: Roger
authors.initials: R
authors.lastname: Nadrowitz
authors.forename: Inga
authors.initials: I
authors.lastname: Buchmann
authors.forename: Peter
authors.initials: P
authors.lastname: Hunold
authors.forename: Frank
authors.initials: F
authors.lastname: Noack
authors.forename: Steven E
authors.initials: SE
authors.lastname: Schild
authors.forename: Birgit
authors.initials: B
authors.lastname: Meller
mesh_terms: D000911:Antibodies, Monoclonal / Q000008:administration & dosage* / Q000493:pharmacokinetics*; D061067:Antibodies, Monoclonal, Humanized; D000970:Antineoplastic Agents / Q000008:administration & dosage* / Q000493:pharmacokinetics*; D001812:Blood-Brain Barrier / Q000000981:diagnostic imaging*; D001932:Brain Neoplasms / Q000175:diagnosis / Q000188:drug therapy / Q000532:radiotherapy / Q000556:secondary*; D002289:Carcinoma, Non-Small-Cell Lung / Q000175:diagnosis / Q000188:drug therapy / Q000532:radiotherapy / Q000556:secondary*; D000068818:Cetuximab; D016371:Cranial Irradiation; D006801:Humans; D007091:Image Processing, Computer-Assisted; D007457:Iodine Radioisotopes; D008175:Lung Neoplasms / Q000175:diagnosis / Q000188:drug therapy* / Q000532:radiotherapy*; D008279:Magnetic Resonance Imaging; D008297:Male; D008875:Middle Aged; D011877:Radionuclide Imaging; D015899:Tomography, Emission-Computed, Single-Photon
chemical_list: D000911:Antibodies, Monoclonal; D061067:Antibodies, Monoclonal, Humanized; D000970:Antineoplastic Agents; D007457:Iodine Radioisotopes; D000068818:Cetuximab
references.citation: Cancer Res. 1999 Apr 15;59(8):1935-40
references.pmid: 10213503
references.citation: Strahlenther Onkol. 2008 Jan;184(1):30-5
references.pmid: 18188520
references.citation: J Clin Oncol. 2002 Sep 1;20(17):3644-50
references.pmid: 12202665
references.citation: Strahlenther Onkol. 2008 Dec;184(12):655-62
references.pmid: 19107346
references.citation: Ann Oncol. 2001 Jan;12(1):59-67
references.pmid: 11249050
references.citation: Clin Cancer Res. 2000 Jun;6(6):2166-74
references.pmid: 10873065
references.citation: J Clin Oncol. 1989 Jul;7(7):916-22
references.pmid: 2544685
references.citation: Cancer. 2007 Sep 1;110(5):1077-82
references.pmid: 17614294
references.citation: Cancer. 1996 Oct 15;78(8):1781-8
references.pmid: 8859192
references.citation: Strahlenther Onkol. 2009 Dec;185(12):775-81
references.pmid: 20013086
references.citation: J Clin Oncol. 2000 Oct 1;18(19):3400-8
references.pmid: 11013281
references.citation: Int J Radiat Oncol Biol Phys. 2005 Jan 1;61(1):185-91
references.pmid: 15629610
references.citation: Strahlenther Onkol. 2008 Nov;184(11):565-71
references.pmid: 19016014
references.citation: Eur J Cancer Clin Oncol. 1988 Feb;24(2):131-5
references.pmid: 3356201
references.citation: Clin Cancer Res. 2001 Oct;7(10):2958-70
references.pmid: 11595683
references.citation: Strahlenther Onkol. 2008 May;184(5):251-5
references.pmid: 18427755
references.citation: Int J Radiat Oncol Biol Phys. 2009 Nov 15;75(4):1226-31
references.pmid: 19356858
references.citation: N Engl J Med. 2006 Feb 9;354(6):567-78
references.pmid: 16467544