title: PET of EGFR with (64) Cu-cetuximab-F(ab')2 in mice with head and neck squamous cell carcinoma xenografts.
abstract: Overexpression of the epidermal growth factor receptor (EGFR) is linked to an adverse outcome in various solid tumors. Cetuximab is an EGFR inhibitor, which in combination with radiotherapy improves locoregional control and survival in a subgroup of patients with head and neck squamous cell carcinomas (HNSCCs). The aim of this study was to develop and characterize an EGFR-directed PET tracer, (64) Cu-cetuximab-F(ab')2, to determine the systemic accessibility of EGFR. Mice with HNSCC xenografts, UT-SCC-8 (n = 6) or UT-SCC-45 (n = 6), were imaged 24 h post injection with (64) Cu-NODAGA-cetuximab-F(ab')2 using PET/CT. One mouse for each tumor model was co-injected with excess unlabeled cetuximab 3 days before radiotracer injection to determine non-EGFR-mediated uptake. Ex vivo biodistribution of the tracer was determined and tumors were analyzed by autoradiography and immunohistochemistry. The SUVmax of UT-SCC-8 tumors was higher than that of UT-SCC-45: 1.5 ± 1.0 and 0.8 ± 0.2 (p < 0.05), respectively. SUVmax after in vivo blocking of EGFR with cetuximab was 0.4. Immunohistochemistry showed that UT-SCC-8 had a significantly higher EGFR expression than UT-SCC-45: 0.50 ± 0.19 versus 0.12 ± 0.08 (p < 0.005), respectively. Autoradiography indicated that (64) Cu-cetuximab-F(ab')2 uptake correlated with EGFR expression in both tumors: r = 0.86 ± 0.06 (UT-SCC-8) and 0.90 ± 0.06 (UT-SCC-45). (64) Cu-cetuximab-F(ab')2 is a promising PET tracer to determine expression of EGFR in vivo. Clinically, this tracer has the potential to be used to determine cetuximab targeting of tumors and possibly to non-invasively monitor the response to EGFR-inhibitor treatment.
authors.affiliation: Department of Radiation Oncology, Radboud University Medical Center, Nijmegen, The Netherlands.|Department of Radiology and Nuclear Medicine, Radboud University Medical Center, Nijmegen, The Netherlands.
authors.forename: Laura K
authors.initials: LK
authors.lastname: van Dijk
authors.affiliation: Radiopharmaceutical Chemistry Laboratory, Turku PET Centre, University of Turku, Turku, Finland.
authors.forename: Cheng-Bin
authors.initials: CB
authors.lastname: Yim
authors.affiliation: Department of Radiology and Nuclear Medicine, Radboud University Medical Center, Nijmegen, The Netherlands.
authors.forename: Gerben M
authors.initials: GM
authors.lastname: Franssen
authors.affiliation: Department of Radiation Oncology, Radboud University Medical Center, Nijmegen, The Netherlands.
authors.forename: Johannes H A M
authors.initials: JH
authors.lastname: Kaanders
authors.affiliation: Accelerator Laboratory, Turku PET Centre, Åbo Akademi University, Turku, Finland.
authors.forename: Johan
authors.initials: J
authors.lastname: Rajander
authors.affiliation: Radiopharmaceutical Chemistry Laboratory, Turku PET Centre, University of Turku, Turku, Finland.|Accelerator Laboratory, Turku PET Centre, Åbo Akademi University, Turku, Finland.
authors.forename: Olof
authors.initials: O
authors.lastname: Solin
authors.affiliation: MediCity/PET Preclinical Laboratory, Turku PET Centre, University of Turku, Turku, Finland.
authors.forename: Tove J
authors.initials: TJ
authors.lastname: Grönroos
authors.affiliation: Department of Radiology and Nuclear Medicine, Radboud University Medical Center, Nijmegen, The Netherlands.
authors.forename: Otto C
authors.initials: OC
authors.lastname: Boerman
authors.affiliation: Department of Radiation Oncology, Radboud University Medical Center, Nijmegen, The Netherlands.
authors.forename: Johan
authors.initials: J
authors.lastname: Bussink
mesh_terms: D000818:Animals; D002294:Carcinoma, Squamous Cell / Q000000981:diagnostic imaging* / Q000188:drug therapy / Q000473:pathology; D045744:Cell Line, Tumor; D000068818:Cetuximab / Q000008:administration & dosage / Q000737:chemistry; D003287:Contrast Media / Q000008:administration & dosage* / Q000737:chemistry; D003301:Copper Radioisotopes / Q000008:administration & dosage / Q000737:chemistry; D066246:ErbB Receptors / Q000096:biosynthesis / Q000737:chemistry / Q000302:isolation & purification*; D006258:Head and Neck Neoplasms / Q000000981:diagnostic imaging* / Q000188:drug therapy / Q000473:pathology; D006801:Humans; D051379:Mice; D049268:Positron-Emission Tomography; D011859:Radiography; D000077195:Squamous Cell Carcinoma of Head and Neck; D023041:Xenograft Model Antitumor Assays
chemical_list: D003287:Contrast Media; D003301:Copper Radioisotopes; C512478:EGFR protein, human; D066246:ErbB Receptors; D000068818:Cetuximab
keywords: 64Cu; EGFR; F(ab')2; HNSCC; PET/CT; cetuximab