Document Detail


Development and characterization of 89Zr-labeled panitumumab for immuno-positron emission tomographic imaging of the epidermal growth factor receptor.
MedLine Citation:
PMID:  23348788     Owner:  NLM     Status:  MEDLINE    
Abstract/OtherAbstract:
The epidermal growth factor receptor (EGFR) is overexpressed in the majority of malignancies and has been associated with poor outcomes. Panitumumab, an anti-EGFR monoclonal antibody that binds to the extracellular binding domain of EGFR, is increasingly used with radiotherapy and chemotherapy but has associated toxicities. The purpose of this study was to develop and characterize a novel targeted imaging agent for the EGFR using radiolabeled panitumumab. Flow cytometry studies were performed to evaluate EGFR expression in several cell lines. Desferrioxamine-Bz-NCS (DFO) was conjugated to panitumumab and labeled with (89)Zr. Cell uptake studies were performed in four cell lines. For biodistribution studies and micro-positron emission tomography/computed tomography (PET/CT), mouse xenograft models were generated using the same cell lines. PET was performed, and tumors and select organs were harvested for biodistribution studies. Panitumumab was radiolabeled with (89)Zr with high radiochemical purity and specific activity and was found to be stable in serum. Cell binding studies demonstrated that radiotracer uptake in cells correlated with the degree of EGFR expression. MicroPET/CT imaging studies demonstrated a high intensity of (89)Zr-panitumumab in A431 and HCT 116 tumors in comparison with the EGFR-negative tumors. Biodistribution studies confirmed the results from the imaging studies. (89)Zr-panitumumab imaging of EGFR-positive tumors demonstrated levels of radiotracer uptake associated with EGFR expression.
Authors:
Albert J Chang; Ravindra A De Silva; Suzanne E Lapi
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Publication Detail:
Type:  Journal Article    
Journal Detail:
Title:  Molecular imaging     Volume:  12     ISSN:  1536-0121     ISO Abbreviation:  Mol Imaging     Publication Date:    2013 Jan-Feb
Date Detail:
Created Date:  2013-01-25     Completed Date:  2013-07-08     Revised Date:  2014-03-11    
Medline Journal Info:
Nlm Unique ID:  101120118     Medline TA:  Mol Imaging     Country:  United States    
Other Details:
Languages:  eng     Pagination:  17-27     Citation Subset:  IM    
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MeSH Terms
Descriptor/Qualifier:
Animals
Antibodies, Monoclonal / chemistry,  pharmacokinetics*
Cell Line, Tumor
Drug Stability
Flow Cytometry
Humans
Immunohistochemistry / methods*
Mice
Mice, Nude
Multimodal Imaging
Positron-Emission Tomography / methods*
Radioisotopes / chemistry,  pharmacokinetics*
Receptor, Epidermal Growth Factor / analysis,  metabolism*
Tissue Distribution
Tomography, X-Ray Computed
Transplantation, Heterologous
Zirconium / chemistry,  pharmacokinetics*
Grant Support
ID/Acronym/Agency:
P30 CA091842/CA/NCI NIH HHS
Chemical
Reg. No./Substance:
0/Antibodies, Monoclonal; 0/Radioisotopes; 0/panitumumab; C6V6S92N3C/Zirconium; EC 2.7.10.1/EGFR protein, human; EC 2.7.10.1/Receptor, Epidermal Growth Factor

From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine


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