title: 99mTc-Hydrazinonicotinamide epidermal growth factor-polyethylene glycol-quantum dot imaging allows quantification of breast cancer epidermal growth factor receptor expression and monitors receptor downregulation in response to cetuximab therapy.
abstract: Therapy of cancer, including basallike breast tumors, that targets the epidermal growth factor receptor (EGFR) would greatly benefit from noninvasive methods that can quantitatively monitor receptor status and treatment response.
  
  
  METHODS
  Here, we investigated the potential of a novel technique based on streptavidin cadmium selenide/zinc sulfide quantum dots (Qdots) multiplexed with polyethylene glycol (PEG), epidermal growth factor (EGF), and (99m)Tc-hydrazinonicotinamide. In vitro binding affinity and specificity were evaluated in cultured cells. Biodistribution studies and in vivo imaging were performed in murine breast tumor xenografts of basallike phenotype MDA-MB-468 cells and EGFR-negative cells.
  
  
  RESULTS
  (99m)Tc-hydrazinonicotinamide EGF-PEG-Qdot showed specific and high-affinity EGFR targeting on confocal microscopy, immunoblotting, and binding assays. When intravenously injected, MDA-MB-468 tumors were visualized with high contrast by both optical and scintigraphic imaging. Scintigraphic image-based quantification correctly discriminated high-EGFR-expressing MDA-MB-468 tumors from other tumors, and image-based tumor uptake closely correlated to EGFR content. Importantly, serial imaging of MDA-MB-468 tumors responding to cetuximab therapy could detect a significant reduction of tumor uptake that was paralleled by downregulation of EGFR expression. Furthermore, high baseline uptake predicted good response to cetuximab therapy.
  
  
  CONCLUSIONS
  (99m)Tc-hydrazinonicotinamide EGF-PEG-Qdot provides EGFR-targeted imaging of breast tumors and may allow noninvasive monitoring of EGFR status in living subjects before and after targeted therapies.
authors.affiliation: Department of Nuclear Medicine, Samsung Medical Center, Sungkyunkwan University School of Medicine, Seoul, Korea.
authors.forename: Kyung-Ho
authors.initials: KH
authors.lastname: Jung
authors.forename: Yearn Seong
authors.initials: YS
authors.lastname: Choe
authors.forename: Jin-Young
authors.initials: JY
authors.lastname: Paik
authors.forename: Kyung-Han
authors.initials: KH
authors.lastname: Lee
mesh_terms: D000818:Animals; D000911:Antibodies, Monoclonal / Q000627:therapeutic use*; D061067:Antibodies, Monoclonal, Humanized; D000970:Antineoplastic Agents / Q000627:therapeutic use*; D015153:Blotting, Western; D001943:Breast Neoplasms / Q000000981:diagnostic imaging* / Q000378:metabolism*; D045744:Cell Line, Tumor; D000068818:Cetuximab; D015536:Down-Regulation / Q000187:drug effects; D004815:Epidermal Growth Factor / Q000493:pharmacokinetics; D066246:ErbB Receptors / Q000187:drug effects* / Q000378:metabolism*; D005260:Female; D006801:Humans; D051379:Mice; D018613:Microscopy, Confocal; D046529:Microscopy, Electron, Transmission; D015609:Organotechnetium Compounds / Q000493:pharmacokinetics; D011092:Polyethylene Glycols / Q000493:pharmacokinetics; D045663:Quantum Dots; D011877:Radionuclide Imaging; D019275:Radiopharmaceuticals / Q000493:pharmacokinetics; D014018:Tissue Distribution; D023041:Xenograft Model Antitumor Assays
chemical_list: D000911:Antibodies, Monoclonal; D061067:Antibodies, Monoclonal, Humanized; D000970:Antineoplastic Agents; D015609:Organotechnetium Compounds; D019275:Radiopharmaceuticals; D011092:Polyethylene Glycols; D004815:Epidermal Growth Factor; D066246:ErbB Receptors; D000068818:Cetuximab