title: PET imaging of epidermal growth factor receptor expression in tumours using 89Zr-labelled ZEGFR:2377 affibody molecules.
abstract: Epidermal growth factor receptor (EGFR) is a transmembrane tyrosine kinase receptor, which is overexpressed in many types of cancer. The use of EGFR-targeting monoclonal antibodies and tyrosine-kinase inhibitors improves significantly survival of patients with colorectal, non-small cell lung cancer and head and neck squamous cell carcinoma. Detection of EGFR overexpression provides important prognostic and predictive information influencing management of the patients. The use of radionuclide molecular imaging would enable non-invasive repeatable determination of EGFR expression in disseminated cancer. Moreover, positron emission tomography (PET) would provide superior sensitivity and quantitation accuracy in EGFR expression imaging. Affibody molecules are a new type of imaging probes, providing high contrast in molecular imaging. In the present study, an EGFR-binding affibody molecule (ZEGFR:2377) was site-specifically conjugated with a deferoxamine (DFO) chelator and labelled under mild conditions (room temperature and neutral pH) with a positron-emitting radionuclide (89)Zr. The (89)Zr-DFO-ZEGFR:2377 tracer demonstrated specific high affinity (160 ± 60 pM) binding to EGFR-expressing A431 epidermoid carcinoma cell line. In mice bearing A431 xenografts, (89)Zr-DFO-ZEGFR:2377 demonstrated specific uptake in tumours and EGFR-expressing tissues. The tracer provided tumour uptake of 2.6 ± 0.5% ID/g and tumour-to-blood ratio of 3.7 ± 0.6 at 24 h after injection. (89)Zr-DFO-ZEGFR:2377 provides higher tumour-to-organ ratios than anti-EGFR antibody (89)Zr-DFO-cetuximab at 48 h after injection. EGFR‑expressing tumours were clearly visualized by microPET using (89)Zr-DFO-ZEGFR:2377 at both 3 and 24 h after injection. In conclusion, 8(9)Zr-DFO-ZEGFR:2377 is a potential probe for PET imaging of EGFR-expression in vivo.
authors: Institute of Immunology, Genetic and Pathology, Uppsala University, SE-75185 Uppsala, Sweden.
authors: Javad
authors: J
authors: Garousi
authors: Division of Protein Technology, KTH Royal Institute of Technology, SE-10691 Stockholm, Sweden.
authors: Ken G
authors: KG
authors: Andersson
authors: Division of Molecular Imaging, Department of Medicinal Chemistry, Uppsala University, SE-751 83 Uppsala, Sweden.
authors: Bogdan
authors: B
authors: Mitran
authors: Institute of Immunology, Genetic and Pathology, Uppsala University, SE-75185 Uppsala, Sweden.
authors: Marie-Louise
authors: ML
authors: Pichl
authors: Division of Protein Technology, KTH Royal Institute of Technology, SE-10691 Stockholm, Sweden.
authors: Stefan
authors: S
authors: Ståhl
authors: Division of Molecular Imaging, Department of Medicinal Chemistry, Uppsala University, SE-751 83 Uppsala, Sweden.
authors: Anna
authors: A
authors: Orlova
authors: Division of Protein Technology, KTH Royal Institute of Technology, SE-10691 Stockholm, Sweden.
authors: John
authors: J
authors: Löfblom
authors: Institute of Immunology, Genetic and Pathology, Uppsala University, SE-75185 Uppsala, Sweden.
authors: Vladimir
authors: V
authors: Tolmachev
mesh_terms: D000818:Animals; D000911:Antibodies, Monoclonal / Q000008:administration & dosage*; D002289:Carcinoma, Non-Small-Cell Lung / Q000000981:diagnostic imaging* / Q000473:pathology; D045744:Cell Line, Tumor; D066246:ErbB Receptors / Q000037:antagonists & inhibitors / Q000096:biosynthesis* / Q000235:genetics; D015972:Gene Expression Regulation, Neoplastic; D006801:Humans; D051379:Mice; D057054:Molecular Imaging; D049268:Positron-Emission Tomography; D023041:Xenograft Model Antitumor Assays; D015040:Zirconium / Q000737:chemistry
chemical_list: D000911:Antibodies, Monoclonal; D015040:Zirconium; C512478:EGFR protein, human; D066246:ErbB Receptors