HOMEPRODUCTSCOMPANYCONTACTFAQResearchDictionaryPharmaSign Up FREE or Login

PET imaging of EGFR expression in nude mice bearing MDA-MB-468, a human breast adenocarcinoma.

AbstractBACKGROUND AND 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).
CONCLUSION:
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.
AuthorsKayvan Sadri, Qing Ren, Kaijun Zhang, Bishnuhari Paudyal, Devakumar Devadhas, Ulrich Rodeck, Mathew Thakur
JournalNuclear medicine communications (Nucl Med Commun) Vol. 32 Issue 7 Pg. 563-9 (Jul 2011) ISSN: 1473-5628 [Electronic] England
PMID21572364 (Publication Type: Journal Article)
Chemical References
  • 64Cu-DOTA-cetuximab
  • Antibodies, Monoclonal
  • Organometallic Compounds
  • ErbB Receptors
  • Cetuximab
Topics
  • Adenocarcinoma (diagnostic imaging, genetics, metabolism, pathology)
  • Animals
  • Antibodies, Monoclonal (chemistry, metabolism, pharmacokinetics)
  • Breast Neoplasms (diagnostic imaging, genetics, metabolism, pathology)
  • Cell Line, Tumor
  • Cell Transformation, Neoplastic
  • Cetuximab
  • ErbB Receptors (metabolism)
  • Gene Expression Regulation, Neoplastic
  • Humans
  • Mice
  • Mice, Nude
  • Neoplasm Transplantation
  • Organometallic Compounds (chemistry, metabolism, pharmacokinetics)
  • Positron-Emission Tomography (methods)
  • Radiochemistry
  • Time Factors

Join CureHunter, for free Research Interface BASIC access!

Take advantage of free CureHunter research engine access to explore the best drug and treatment options for any disease. Find out why thousands of doctors, pharma researchers and patient activists around the world use CureHunter every day.
Realize the full power of the drug-disease research graph!


Choose Username:
Email:
Password:
Verify Password:
Enter Code Shown: