title: ImmunoPET with Anti-Mesothelin Antibody in Patients with Pancreatic and Ovarian Cancer before Anti-Mesothelin Antibody-Drug Conjugate Treatment.
abstract: OBJECTIVE
  Mesothelin (MSLN) is frequently overexpressed in pancreatic and ovarian cancers, making it a potential drug target. We performed an (89)Zr-PET imaging study with MMOT0530A, a MSLN antibody, in conjunction with a phase I study with the antibody-drug conjugate DMOT4039A, containing MMOT0530A bound to MMAE. The aim was to study antibody tumor uptake, whole-body distribution, and relation between uptake, response to treatment, and MSLN expression.
  
  
  METHODS
  Before DMOT4039A treatment, patients received 37 MBq (89)Zr-MMOT0530A followed by PET/CT imaging 2, 4, and 7 days postinjection. Tracer uptake was expressed as standardized uptake value (SUV). MSLN expression was determined with immunohistochemistry (IHC) on archival tumor tissue.
  
  
  RESULTS
  Eleven patients were included, 7 with pancreatic and 4 with ovarian cancer. IHC MSLN expression varied from absent to strong. Suitable tracer antibody dose was 10 mg MMOT0530A and optimal imaging time was 4 and 7 days postinjection. Tumor tracer uptake occurred in 37 lesions with mean SUVmax of 13.1 (±7.5) on PET 4 days postinjection, with 11.5 (±7.5) in (N= 17) pancreatic and 14.5 (±8.7) in (N= 20) ovarian cancer lesions. Within patients, a mean 2.4-fold (±1.10) difference in uptake between tumor lesions existed. Uptake in blood, liver, kidneys, spleen, and intestine reflected normal antibody distribution. Tracer tumor uptake was correlated to IHC. Best response to DMOT4039A was partial response in one patient.
  
  
  CONCLUSIONS
  With (89)Zr-MMOT0530A-PET, pancreatic and ovarian cancer lesions as well as antibody biodistribution could be visualized. This technique can potentially guide individualized antibody-based treatment.
authors.affiliation: Department of Medical Oncology, University of Groningen, University Medical Center Groningen, Groningen, the Netherlands.
authors.forename: Laetitia E
authors.initials: LE
authors.lastname: Lamberts
authors.affiliation: Department of Medical Oncology, VU University Medical Center, Amsterdam, the Netherlands.
authors.forename: Catharina W
authors.initials: CW
authors.lastname: Menke-van der Houven van Oordt
authors.affiliation: Department of Medical Oncology, University of Groningen, University Medical Center Groningen, Groningen, the Netherlands. Department of Clinical Pharmacy and Pharmacology, University of Groningen, University Medical Center Groningen, Groningen, the Netherlands.
authors.forename: Eva J
authors.initials: EJ
authors.lastname: ter Weele
authors.affiliation: Department of Medical Oncology, University of Groningen, University Medical Center Groningen, Groningen, the Netherlands.
authors.forename: Frederike
authors.initials: F
authors.lastname: Bensch
authors.affiliation: Department of Medical Oncology, University of Groningen, University Medical Center Groningen, Groningen, the Netherlands.
authors.forename: Michiel M
authors.initials: MM
authors.lastname: Smeenk
authors.affiliation: Department of Medical Oncology, VU University Medical Center, Amsterdam, the Netherlands.
authors.forename: Johannes
authors.initials: J
authors.lastname: Voortman
authors.affiliation: Department of Radiology and Nuclear Medicine, VU University Medical Center, Amsterdam, the Netherlands.
authors.forename: Otto S
authors.initials: OS
authors.lastname: Hoekstra
authors.affiliation: Department of Early Clinical Development, Genentech, Inc. South San Francisco, California.
authors.forename: Simon P
authors.initials: SP
authors.lastname: Williams
authors.affiliation: Department of Biomedical Imaging, Genentech, Inc. South San Francisco, California.
authors.forename: Bernard M
authors.initials: BM
authors.lastname: Fine
authors.affiliation: Department of Biomedical Imaging, Genentech, Inc. South San Francisco, California.
authors.forename: Daniel
authors.initials: D
authors.lastname: Maslyar
authors.affiliation: Department of Nuclear Medicine and Molecular Imaging, University of Groningen, University Medical Center Groningen, Groningen, the Netherlands.
authors.forename: Johan R
authors.initials: JR
authors.lastname: de Jong
authors.affiliation: Department of Medical Oncology, University of Groningen, University Medical Center Groningen, Groningen, the Netherlands.
authors.forename: Jourik A
authors.initials: JA
authors.lastname: Gietema
authors.affiliation: Department of Medical Oncology, University of Groningen, University Medical Center Groningen, Groningen, the Netherlands.
authors.forename: Carolien P
authors.initials: CP
authors.lastname: Schröder
authors.affiliation: Department of Radiology, University of Groningen, University Medical Center Groningen, Groningen, the Netherlands.
authors.forename: Alphons H H
authors.initials: AH
authors.lastname: Bongaerts
authors.affiliation: Department of Clinical Pharmacy and Pharmacology, University of Groningen, University Medical Center Groningen, Groningen, the Netherlands. Department of Nuclear Medicine and Molecular Imaging, University of Groningen, University Medical Center Groningen, Groningen, the Netherlands.
authors.forename: Marjolijn N
authors.initials: MN
authors.lastname: Lub-de Hooge
authors.affiliation: Department of Medical Oncology, VU University Medical Center, Amsterdam, the Netherlands.
authors.forename: Henk M W
authors.initials: HM
authors.lastname: Verheul
authors.affiliation: Department of Biomedical Imaging, Genentech, Inc. South San Francisco, California.
authors.forename: Sandra M
authors.initials: SM
authors.lastname: Sanabria Bohorquez
authors.affiliation: Department of Nuclear Medicine and Molecular Imaging, University of Groningen, University Medical Center Groningen, Groningen, the Netherlands.
authors.forename: Andor W J M
authors.initials: AW
authors.lastname: Glaudemans
authors.affiliation: Department of Medical Oncology, University of Groningen, University Medical Center Groningen, Groningen, the Netherlands. e.g.e.de.vries@umcg.nl.
authors.forename: Elisabeth G E
authors.initials: EG
authors.lastname: de Vries
mesh_terms: D000328:Adult; D000368:Aged; D000911:Antibodies, Monoclonal / Q000276:immunology; D000951:Antigens, Neoplasm / Q000276:immunology; D005260:Female; D058851:GPI-Linked Proteins / Q000276:immunology; D006801:Humans; D018796:Immunoconjugates / Q000276:immunology / Q000627:therapeutic use*; D008297:Male; D000090204:Mesothelin; D008875:Middle Aged; D010051:Ovarian Neoplasms / Q000175:diagnosis* / Q000188:drug therapy* / Q000276:immunology; D010190:Pancreatic Neoplasms / Q000175:diagnosis* / Q000188:drug therapy* / Q000276:immunology; D049268:Positron-Emission Tomography / Q000379:methods*; D014057:Tomography, X-Ray Computed; D016896:Treatment Outcome; D015040:Zirconium
chemical_list: D000911:Antibodies, Monoclonal; D000951:Antigens, Neoplasm; D058851:GPI-Linked Proteins; D018796:Immunoconjugates; C000715527:MSLN protein, human; D015040:Zirconium; D000090204:Mesothelin