title: Quantitative assessment of Zirconium-89 labeled cetuximab using PET/CT imaging in patients with advanced head and neck cancer: a theragnostic approach.
abstract: Biomarkers predicting treatment response to the monoclonal antibody cetuximab in locally advanced head and neck squamous cell carcinomas (LAHNSCC) are lacking. We hypothesize that tumor accessibility is an important factor in treatment success of the EGFR targeting drug. We quantified uptake of cetuximab labeled with Zirconium-89 (89Zr) using PET/CT imaging.Seventeen patients with stage III-IV LAHNSCC received a loading dose unlabeled cetuximab, followed by 10 mg 54.5±9.6 MBq 89Zr-cetuximab. PET/CT images were acquired either 3 and 6 or 4 and 7 days post-injection. 89Zr-cetuximab uptake was quantified using standardized uptake value (SUV) and tumor-to-background ratio (TBR), and correlated to EGFR immunohistochemistry. TBR was compared between scan days to determine optimal timing.Uptake of 89Zr-cetuximab varied between patients (day 6-7: SUVpeak range 2.5-6.2). TBR increased significantly (49±28%, p < 0.01) between first (1.1±0.3) and second scan (1.7±0.6). Between groups with a low and high EGFR expression a significant difference in SUVmean (2.1 versus 3.0) and SUVpeak (3.2 versus 4.7) was found, however, not in TBR. Data is available at www.cancerdata.org (DOI: 10.17195/candat.2016.11.1).In conclusion, 89Zr-cetuximab PET imaging shows large inter-patient variety in LAHNSCC and provides additional information over FDG-PET and EGFR expression. Validation of the predictive value is recommended with scans acquired 6-7 days post-injection.
authors.affiliation: Department of Radiation Oncology (MAASTRO), GROW-School for Oncology and Developmental Biology, Maastricht University Medical Center, Maastricht, The Netherlands.
authors.forename: Aniek J G
authors.initials: AJ
authors.lastname: Even
authors.affiliation: Department of Radiation Oncology, The Netherlands Cancer Institute, Amsterdam, The Netherlands.
authors.forename: Olga
authors.initials: O
authors.lastname: Hamming-Vrieze
authors.affiliation: Department of Radiation Oncology (MAASTRO), GROW-School for Oncology and Developmental Biology, Maastricht University Medical Center, Maastricht, The Netherlands.
authors.forename: Wouter
authors.initials: W
authors.lastname: van Elmpt
authors.affiliation: Department of Pathology, Maastricht University Medical Centre, Maastricht, The Netherlands.
authors.forename: Véronique J L
authors.initials: VJ
authors.lastname: Winnepenninckx
authors.affiliation: Department of Radiation Oncology, The Netherlands Cancer Institute, Amsterdam, The Netherlands.
authors.forename: Jolien
authors.initials: J
authors.lastname: Heukelom
authors.affiliation: Department of Medical Oncology, The Netherlands Cancer Institute, Amsterdam, The Netherlands.
authors.forename: Margot E T
authors.initials: ME
authors.lastname: Tesselaar
authors.affiliation: Department of Radiation Oncology, The Netherlands Cancer Institute, Amsterdam, The Netherlands.|Department of Nuclear Medicine, The Netherlands Cancer Institute, Amsterdam, The Netherlands.
authors.forename: Wouter V
authors.initials: WV
authors.lastname: Vogel
authors.affiliation: Department of Medical Oncology, GROW-School for Oncology and Developmental Biology, Maastricht University Medical Center, Maastricht, The Netherlands.
authors.forename: Ann
authors.initials: A
authors.lastname: Hoeben
authors.affiliation: Department of Radiation Oncology (MAASTRO), GROW-School for Oncology and Developmental Biology, Maastricht University Medical Center, Maastricht, The Netherlands.
authors.forename: Catharina M L
authors.initials: CM
authors.lastname: Zegers
authors.affiliation: Department of Radiology and Nuclear Medicine, VU University Medical Center, Amsterdam, The Netherlands.
authors.forename: Daniëlle J
authors.initials: DJ
authors.lastname: Vugts
authors.affiliation: Department of Radiology and Nuclear Medicine, VU University Medical Center, Amsterdam, The Netherlands.
authors.forename: Guus A M S
authors.initials: GA
authors.lastname: van Dongen
authors.affiliation: Department of Radiation Oncology, The Netherlands Cancer Institute, Amsterdam, The Netherlands.
authors.forename: Harry
authors.initials: H
authors.lastname: Bartelink
authors.affiliation: Department of Nuclear Medicine, Maastricht University Medical Center, Maastricht, The Netherlands.|Department of Nuclear Medicine, University Hospital, RWTH Aachen University, Aachen, Germany.
authors.forename: Felix M
authors.initials: FM
authors.lastname: Mottaghy
authors.affiliation: Department of Radiation Oncology (MAASTRO), GROW-School for Oncology and Developmental Biology, Maastricht University Medical Center, Maastricht, The Netherlands.
authors.forename: Frank
authors.initials: F
authors.lastname: Hoebers
authors.affiliation: Department of Radiation Oncology (MAASTRO), GROW-School for Oncology and Developmental Biology, Maastricht University Medical Center, Maastricht, The Netherlands.
authors.forename: Philippe
authors.initials: P
authors.lastname: Lambin
mesh_terms: D000368:Aged; D000074322:Antineoplastic Agents, Immunological / Q000008:administration & dosage* / Q000737:chemistry; D000068818:Cetuximab / Q000008:administration & dosage / Q000737:chemistry / Q000493:pharmacokinetics*; D066246:ErbB Receptors / Q000378:metabolism; D005260:Female; D006258:Head and Neck Neoplasms / Q000000981:diagnostic imaging / Q000188:drug therapy* / Q000378:metabolism / Q000473:pathology; D006801:Humans; D008297:Male; D008875:Middle Aged; D057054:Molecular Imaging; D009367:Neoplasm Staging; D000072078:Positron Emission Tomography Computed Tomography / Q000379:methods*; D011868:Radioisotopes / Q000737:chemistry*; D016896:Treatment Outcome; D015040:Zirconium / Q000737:chemistry*
chemical_list: D000074322:Antineoplastic Agents, Immunological; D011868:Radioisotopes; D015040:Zirconium; C512478:EGFR protein, human; D066246:ErbB Receptors; C000615502:Zirconium-89; D000068818:Cetuximab
keywords: EGFR; LAHNSCC; Zirconium-89; cetuximab; immuno-PET