title: First-in-human molecular imaging of HER2 expression in breast cancer metastases using the 111In-ABY-025 affibody molecule.
abstract: The expression status of human epidermal growth factor receptor type 2 (HER2) predicts the response of HER2-targeted therapy in breast cancer. ABY-025 is a small reengineered Affibody molecule targeting a unique epitope of the HER2 receptor, not occupied by current therapeutic agents. This study evaluated the distribution, safety, dosimetry, and efficacy of (111)In-ABY-025 for determining the HER2 status in metastatic breast cancer.
  
  
  METHODS
  Seven patients with metastatic breast cancer and HER2-positive (n = 5) or -negative (n = 2) primary tumors received an intravenous injection of approximately 100 μg (∼ 140 MBq) of (111)In-ABY-025. Planar γ-camera imaging was performed after 30 min, followed by SPECT/CT after 4, 24, and 48 h. Blood levels of radioactivity, antibodies, shed serum HER2, and toxicity markers were evaluated. Lesional HER2 status was verified by biopsies. The metastases were located by (18)F-FDG PET/CT 5 d before (111)In-ABY-025 imaging.
  
  
  RESULTS
  Injection of (111)In-ABY-025 yielded a mean effective dose of 0.15 mSv/MBq and was safe, well tolerated, and without drug-related adverse events. Fast blood clearance allowed high-contrast HER2 images within 4-24 h. No anti-ABY-025 antibodies were observed. When metastatic uptake at 24 h was normalized to uptake at 4 h, the ratio increased in HER2-positive metastases and decreased in negative ones (P < 0.05), with no overlap and confirmation by biopsies. In 1 patient, with HER2-positive primary tumor, (111)In-ABY-025 imaging correctly suggested a HER2-negative status of the metastases. The highest normal-tissue uptake was in the kidneys, followed by the liver and spleen.
  
  
  CONCLUSIONS
  (111)In-ABY-025 appears safe for use in humans and is a promising noninvasive tool for discriminating HER2 status in metastatic breast cancer, regardless of ongoing HER2-targeted antibody treatment.
authors.affiliation: Nuclear Medicine and PET, Department of Radiology, Oncology, and Radiation Sciences, Uppsala University, Uppsala, Sweden.
authors.forename: Jens
authors.initials: J
authors.lastname: Sörensen
authors.forename: Dan
authors.initials: D
authors.lastname: Sandberg
authors.forename: Mattias
authors.initials: M
authors.lastname: Sandström
authors.forename: Anders
authors.initials: A
authors.lastname: Wennborg
authors.forename: Joachim
authors.initials: J
authors.lastname: Feldwisch
authors.forename: Vladimir
authors.initials: V
authors.lastname: Tolmachev
authors.forename: Gunnar
authors.initials: G
authors.lastname: Åström
authors.forename: Mark
authors.initials: M
authors.lastname: Lubberink
authors.forename: Ulrike
authors.initials: U
authors.lastname: Garske-Román
authors.forename: Jörgen
authors.initials: J
authors.lastname: Carlsson
authors.forename: Henrik
authors.initials: H
authors.lastname: Lindman
mesh_terms: D000368:Aged; D001706:Biopsy; D001943:Breast Neoplasms / Q000000981:diagnostic imaging* / Q000473:pathology*; D000939:Epitopes / Q000737:chemistry; D005260:Female; D015902:Gamma Cameras; D020869:Gene Expression Profiling; D006801:Humans; D007205:Indium Radioisotopes / Q000493:pharmacokinetics; D007668:Kidney / Q000187:drug effects; D008099:Liver / Q000187:drug effects; D008875:Middle Aged; D057054:Molecular Imaging; D064847:Multimodal Imaging; D009362:Neoplasm Metastasis; D010446:Peptide Fragments / Q000737:chemistry* / Q000493:pharmacokinetics; D011874:Radiometry; D018719:Erb-b2 Receptor Tyrosine Kinases / Q000378:metabolism*; D011993:Recombinant Fusion Proteins / Q000737:chemistry; D013154:Spleen / Q000187:drug effects; D013205:Staphylococcal Protein A / Q000737:chemistry*; D013997:Time Factors; D015899:Tomography, Emission-Computed, Single-Photon; D014057:Tomography, X-Ray Computed
chemical_list: D000939:Epitopes; D007205:Indium Radioisotopes; D010446:Peptide Fragments; D018719:Erb-b2 Receptor Tyrosine Kinases; D011993:Recombinant Fusion Proteins; D013205:Staphylococcal Protein A; C549680:ABY-025; C508053:ERBB2 protein, human
keywords: 111In imaging; Affibody; HER2 receptor; breast cancer metastases; clinical study