title: 111In-benzyl-DTPA-ZHER2:342, an affibody-based conjugate for in vivo imaging of HER2 expression in malignant tumors.
abstract: Data on expression of the HER2 (erbB-2) receptor in breast carcinoma make it possible to select the most efficient treatment. There are strong indications that HER2 expression possesses prognostic and predictive values in ovarian, prostate, and lung carcinomas as well. Visualization of HER2 expression using radionuclide targeting can provide important diagnostic information. The Affibody Z(HER2:342) is a short (approximately 7 kDa) phage-display-selected protein that binds HER2 with an affinity of 22 pmol/L. The goal of this study was to evaluate whether (111)In-labeled HER2:342 can be used for imaging of HER2 overexpression in vivo.
  
  
  METHODS
  Z(HER2:342) was labeled with (111)In via isothiocyanate-benzyl-DTPA (DTPA is diethylenetriaminepentaacetic acid) and the conjugate was characterized in vitro and in vivo.
  
  
  RESULTS
  (111)In-Benzyl-DTPA-Z(HER2:342) preserved the capacity to bind living HER2-expressing cells specifically. The affinity of In-benzyl-DTPA-Z(HER2:342) to HER2 was 21 pmol/L according to surface plasmon resonance measurements. In nude mice bearing HER2-expressing SKOV-3 xenografts, a tumor uptake of 12% +/- 3% injected activity per gram and a tumor-to-blood ratio of about 100 were obtained 4 h after injection. Tumor uptake in vivo was receptor specific, as it could be blocked with an excess of nonlabeled Z(HER2:342). HER2-expressing xenografts were clearly imaged 4 h after injection using a gamma-camera.
  
  
  CONCLUSIONS
  (111)In-Benzyl-DTPA-Z(HER2:342) is a promising candidate for visualization of HER2 expression in carcinomas, using the single-photon detection technique.
authors.affiliation: Division of Biomedical Radiation Sciences, Uppsala University, Uppsala, Sweden. vladimir.tolmachev@bms.uu.se
authors.forename: Vladimir
authors.initials: V
authors.lastname: Tolmachev
authors.forename: Fredrik Y
authors.initials: FY
authors.lastname: Nilsson
authors.forename: Charles
authors.initials: C
authors.lastname: Widström
authors.forename: Karl
authors.initials: K
authors.lastname: Andersson
authors.forename: Daniel
authors.initials: D
authors.lastname: Rosik
authors.forename: Lars
authors.initials: L
authors.lastname: Gedda
authors.forename: Anders
authors.initials: A
authors.lastname: Wennborg
authors.forename: Anna
authors.initials: A
authors.lastname: Orlova
mesh_terms: D000595:Amino Acid Sequence; D000818:Animals; D045744:Cell Line, Tumor; D005260:Female; D006801:Humans; D007205:Indium Radioisotopes; D051379:Mice; D008807:Mice, Inbred BALB C; D008969:Molecular Sequence Data; D009362:Neoplasm Metastasis; D009368:Neoplasm Transplantation; D004369:Pentetic Acid / Q000031:analogs & derivatives* / Q000737:chemistry; D018719:Erb-b2 Receptor Tyrosine Kinases / Q000737:chemistry*; D014018:Tissue Distribution
chemical_list: D007205:Indium Radioisotopes; D004369:Pentetic Acid; D018719:Erb-b2 Receptor Tyrosine Kinases; C511424:111In-benzyl-DTPA-ZHER2:342