title: Biodistribution and Radiation Dosimetry of the Anti-HER2 Affibody Molecule 68Ga-ABY-025 in Breast Cancer Patients.
abstract: (68)Ga-ABY-025 is a radiolabeled Affibody molecule for in vivo diagnosis of human epidermal growth factor receptor 2 (HER2)-positive breast cancer tumors with PET. The aim of the present work was to measure the biodistribution and estimate the radiation dosimetry of (68)Ga-ABY-025 for 2 different peptide mass doses in a single group of patients using dynamic and serial whole-body PET/CT.
  
  
  
  Eight patients with metastatic breast cancer were included. Each patient underwent an abdominal 45-min dynamic and 3 whole-body PET/CT scans at 1, 2, and 4 h after injection of a low peptide dose (LD) and a high peptide dose (HD), with approximately the same amount of radioactivity, in separate investigations 1 wk apart. As input to the absorbed dose calculations, volumes of interest were drawn on all clearly identifiable source organs: liver, kidneys, spleen, descending aorta, and upper large intestine. Absorbed doses were calculated using OLINDA/EXM, version 1.1.
  
  
  
  Of the major organs, the highest radionuclide uptake at 1, 2, and 4 h after injection was observed in the kidneys and liver. The highest absorbed organ doses were seen in the kidneys, followed by the liver for both LD and HD (68)Ga-ABY-025. Absorbed doses to liver and kidneys were slightly but significantly higher for LD. Total effective dose was 0.030 ± 0.003 mSv/MBq for LD and 0.028 ± 0.002 mSv/MBq for HD.
  
  
  
  The effective dose for a typical 200-MBq administration of (68)Ga-ABY-025 is 6.0 mSv for LD and 5.6 mSv for HD. Therefore, from a radiation dosimetry point of view, HD is preferred for PET/CT evaluation of HER2-expressing breast cancer tumors. These effective doses are somewhat higher than earlier published values for other (68)Ga-labeled tracers, such as 0.021 ± 0.003 mSv/MBq for (68)Ga-DOTATATE and (68)Ga-DOTATOC, mainly because of higher uptake in liver and kidney.
authors.affiliation: Nuclear Medicine and PET, Department of Surgical Sciences, Uppsala University, Uppsala, Sweden mattias.sandstrom@akademiska.se.
authors.forename: Mattias
authors.initials: M
authors.lastname: Sandström
authors.affiliation: Nuclear Medicine and PET, Department of Surgical Sciences, Uppsala University, Uppsala, Sweden.
authors.forename: Karolina
authors.initials: K
authors.lastname: Lindskog
authors.affiliation: Nuclear Medicine and PET, Department of Surgical Sciences, Uppsala University, Uppsala, Sweden.
authors.forename: Irina
authors.initials: I
authors.lastname: Velikyan
authors.affiliation: Affibody AB, Solna, Sweden.
authors.forename: Anders
authors.initials: A
authors.lastname: Wennborg
authors.affiliation: Affibody AB, Solna, Sweden Biomedical Radiation Sciences, Rudbeck Laboratory, Department of Immunology, Genetics, and Pathology, Uppsala University, Uppsala, Sweden; and.
authors.forename: Joachim
authors.initials: J
authors.lastname: Feldwisch
authors.affiliation: Nuclear Medicine and PET, Department of Surgical Sciences, Uppsala University, Uppsala, Sweden.
authors.forename: Dan
authors.initials: D
authors.lastname: Sandberg
authors.affiliation: Biomedical Radiation Sciences, Rudbeck Laboratory, Department of Immunology, Genetics, and Pathology, Uppsala University, Uppsala, Sweden; and.
authors.forename: Vladimir
authors.initials: V
authors.lastname: Tolmachev
authors.affiliation: Biomedical Radiation Sciences, Rudbeck Laboratory, Department of Immunology, Genetics, and Pathology, Uppsala University, Uppsala, Sweden; and.
authors.forename: Anna
authors.initials: A
authors.lastname: Orlova
authors.affiliation: Nuclear Medicine and PET, Department of Surgical Sciences, Uppsala University, Uppsala, Sweden.
authors.forename: Jens
authors.initials: J
authors.lastname: Sörensen
authors.affiliation: Biomedical Radiation Sciences, Rudbeck Laboratory, Department of Immunology, Genetics, and Pathology, Uppsala University, Uppsala, Sweden; and.
authors.forename: Jörgen
authors.initials: J
authors.lastname: Carlsson
authors.affiliation: Section of Oncology, Department of Immunology, Genetics, and Pathology, Uppsala, Sweden.
authors.forename: Henrik
authors.initials: H
authors.lastname: Lindman
authors.affiliation: Nuclear Medicine and PET, Department of Surgical Sciences, Uppsala University, Uppsala, Sweden.
authors.forename: Mark
authors.initials: M
authors.lastname: Lubberink
mesh_terms: D001943:Breast Neoplasms / Q000000981:diagnostic imaging* / Q000378:metabolism*; D005710:Gallium Radioisotopes; D006801:Humans; D010446:Peptide Fragments / Q000276:immunology* / Q000493:pharmacokinetics*; D000072078:Positron Emission Tomography Computed Tomography; D011874:Radiometry; D018719:Erb-b2 Receptor Tyrosine Kinases / Q000276:immunology*; D013205:Staphylococcal Protein A / Q000276:immunology*; D014018:Tissue Distribution; D051598:Whole Body Imaging
chemical_list: D005710:Gallium Radioisotopes; D010446:Peptide Fragments; D018719:Erb-b2 Receptor Tyrosine Kinases; D013205:Staphylococcal Protein A; C549680:ABY-025; C508053:ERBB2 protein, human
keywords: 68Ga-gallium; Affibody; HER2-receptor; breast cancer metastases; dosimetry