title: PET imaging of EGFR expression in nude mice bearing MDA-MB-468, a human breast adenocarcinoma.
abstract: OBJECTIVE
  Cetuximab is a monoclonal antibody that binds to and inhibits the epidermal growth factor receptor (EGFR). EGFR overexpression has been observed in a subset of breast cancers. The purpose of this study was to evaluate 64Cu-labeled cetuximab as an imaging agent using MDA-MB-468 breast cancer cells.
  
  
  METHODS
  Cetuximab was coupled with an N-sulfosuccinimide ester of DOTA, purified, and labeled with the positron-emitting nuclide, 64Cu. Receptor-binding specificity and affinity of 64Cu-DOTA-cetuximab were studied using human MDA-MB-468 breast cancer cells, which express high levels of EGFR. Micropositron emission tomography and biodistribution studies were performed in athymic nude mice bearing MDA-MB-468 cell xenografts. Blocking studies with cold cetuximab were also performed to determine the specific binding of cetuximab.
  
  
  RESULTS
  The radiochemical yield was 97.1 ± 1.1%. The specific activity was 1.5 Ci/μm cetuximab and the affinity to EGFR-positive MDA-MB-468 cells was high (KD=0.4 nmol/l). Both biodistribution and micropositron emission tomographic imaging studies with 64Cu-DOTA-cetuximab showed higher tumor uptake at 24 h (20.91 ± 2.49% ID/g, standardized uptake values of 9.6) than at 4 h (11.65 ± 3.89% ID/g, standardized uptake values of 4.9). Tumor uptake was significantly reduced from 20.91 ± 2.49% ID/g at 24 h to 14.42 ± 0.85% ID/g in a 1-h blocking study (P=0.00).
  
  
  CONCLUSIONS
  Cetuximab can be labeled with 64Cu without compromising its biological activity. The tumor uptake was excellent with high tumor/muscle (7.97 ± 1.78 at 4 h, 15.91 ± 6.04 at 24 h) and reasonable tumor/blood (0.5 ± 0.18 at 4 h, 2.12 ± 0.86 at 24 h) ratios. Blocking studies showed the specific binding of the labeled antibody to tumor tissue.
authors.affiliation: Department of Radiology, Thomas Jefferson University, Philadelphia, Pennysylvania 19107, USA.
authors.forename: Kayvan
authors.initials: K
authors.lastname: Sadri
authors.forename: Qing
authors.initials: Q
authors.lastname: Ren
authors.forename: Kaijun
authors.initials: K
authors.lastname: Zhang
authors.forename: Bishnuhari
authors.initials: B
authors.lastname: Paudyal
authors.forename: Devakumar
authors.initials: D
authors.lastname: Devadhas
authors.forename: Ulrich
authors.initials: U
authors.lastname: Rodeck
authors.forename: Mathew
authors.initials: M
authors.lastname: Thakur
mesh_terms: D000230:Adenocarcinoma / Q000000981:diagnostic imaging* / Q000235:genetics / Q000378:metabolism / Q000473:pathology; D000818:Animals; D000911:Antibodies, Monoclonal / Q000737:chemistry / Q000378:metabolism / Q000493:pharmacokinetics; D001943:Breast Neoplasms / Q000000981:diagnostic imaging* / Q000235:genetics* / Q000378:metabolism / Q000473:pathology; D045744:Cell Line, Tumor; D002471:Cell Transformation, Neoplastic; D000068818:Cetuximab; D066246:ErbB Receptors / Q000378:metabolism*; D015972:Gene Expression Regulation, Neoplastic; D006801:Humans; D051379:Mice; D008819:Mice, Nude; D009368:Neoplasm Transplantation; D009942:Organometallic Compounds / Q000737:chemistry / Q000378:metabolism / Q000493:pharmacokinetics; D049268:Positron-Emission Tomography / Q000379:methods*; D011854:Radiochemistry; D013997:Time Factors
chemical_list: C532429:64Cu-DOTA-cetuximab; D000911:Antibodies, Monoclonal; D009942:Organometallic Compounds; D066246:ErbB Receptors; D000068818:Cetuximab