title: (18)F-nanobody for PET imaging of HER2 overexpressing tumors.
abstract: BACKGROUND
  Radiolabeled nanobodies are exciting new probes for molecular imaging due to high affinity, high specificity and fast washout from the blood. Here we present the labeling of an anti-HER2 nanobody with (18)F and its validation for in vivo assessment of HER2 overexpression.
  
  
  METHODS
  The GMP grade anti-HER2 nanobody was labeled with the prosthetic group, N-succinimidyl-4-[(18)F]fluorobenzoate ([(18)F]-SFB), and its biodistribution, tumor targeting and specificity were evaluated in mouse and rat tumor models.
  
  
  RESULTS
  [(18)F]FB-anti-HER2 nanobody was prepared with a 5-15% global yield (decay corrected) and a specific activity of 24.7 ± 8.2 MBq/nmol. In vivo studies demonstrated a high specific uptake for HER2 positive xenografts (5.94 ± 1.17 and 3.74 ± 0.52%IA/g, 1 and 3h p.i.) with high tumor-to-blood and tumor-to-muscle ratios generating high contrast PET imaging. The probe presented fast clearance through the kidneys (4%IA/g at 3h p.i.). [(18)F]FB-anti-HER2 nanobody is able to image HER2 expressing tumors when co-administered with the anti-HER2 therapeutic antibody trastuzumab (Herceptin), indicating the possibility of using the tracer in patients undergoing Herceptin therapy.
  
  
  CONCLUSIONS
  The GMP grade anti-HER2 nanobody was labeled with (18)F. This new PET probe for imaging HER2 overexpression in tumors has ample potential for clinical translation.
authors.affiliation: In vivo Cellular and Molecular Imaging Laboratory (ICMI), Vrije Universiteit Brussel, Brussels, Belgium. Electronic address: cxavier@vub.ac.be.
authors.forename: Catarina
authors.initials: C
authors.lastname: Xavier
authors.affiliation: In vivo Cellular and Molecular Imaging Laboratory (ICMI), Vrije Universiteit Brussel, Brussels, Belgium.
authors.forename: Anneleen
authors.initials: A
authors.lastname: Blykers
authors.affiliation: In vivo Cellular and Molecular Imaging Laboratory (ICMI), Vrije Universiteit Brussel, Brussels, Belgium; Nucleaire Geneeskunde, UZ Brussel, Brussels, Belgium.
authors.forename: Ilse
authors.initials: I
authors.lastname: Vaneycken
authors.affiliation: In vivo Cellular and Molecular Imaging Laboratory (ICMI), Vrije Universiteit Brussel, Brussels, Belgium.
authors.forename: Matthias
authors.initials: M
authors.lastname: D'Huyvetter
authors.affiliation: Nucleaire Geneeskunde, UZ Brussel, Brussels, Belgium.
authors.forename: Jan
authors.initials: J
authors.lastname: Heemskerk
authors.affiliation: In vivo Cellular and Molecular Imaging Laboratory (ICMI), Vrije Universiteit Brussel, Brussels, Belgium; Nucleaire Geneeskunde, UZ Brussel, Brussels, Belgium.
authors.forename: Tony
authors.initials: T
authors.lastname: Lahoutte
authors.affiliation: In vivo Cellular and Molecular Imaging Laboratory (ICMI), Vrije Universiteit Brussel, Brussels, Belgium; Laboratory of Cellular and Molecular Immunology, Vrije Universiteit Brussel, Brussels, Belgium.
authors.forename: Nick
authors.initials: N
authors.lastname: Devoogdt
authors.affiliation: In vivo Cellular and Molecular Imaging Laboratory (ICMI), Vrije Universiteit Brussel, Brussels, Belgium; Nucleaire Geneeskunde, UZ Brussel, Brussels, Belgium.
authors.forename: Vicky
authors.initials: V
authors.lastname: Caveliers
mesh_terms: D000818:Animals; D045744:Cell Line, Tumor; D002471:Cell Transformation, Neoplastic; D004355:Drug Stability; D005260:Female; D005462:Fluorine Radioisotopes; D015972:Gene Expression Regulation, Neoplastic; D006801:Humans; D007553:Isotope Labeling; D051379:Mice; D010051:Ovarian Neoplasms / Q000000981:diagnostic imaging* / Q000378:metabolism* / Q000473:pathology; D049268:Positron-Emission Tomography / Q000379:methods*; D011854:Radiochemistry; D051381:Rats; D018719:Erb-b2 Receptor Tyrosine Kinases / Q000276:immunology / Q000378:metabolism*; D061905:Single-Domain Antibodies / Q000737:chemistry / Q000276:immunology* / Q000378:metabolism; D014018:Tissue Distribution; D014057:Tomography, X-Ray Computed
chemical_list: D005462:Fluorine Radioisotopes; D018719:Erb-b2 Receptor Tyrosine Kinases; D061905:Single-Domain Antibodies
keywords: HER2; Molecular imaging; Nanobodies; PET; [(18)F]-SFB