title: Measuring HER2-Receptor Expression In Metastatic Breast Cancer Using [68Ga]ABY-025 Affibody PET/CT.
abstract: OBJECTIVE
  Positron Emission Tomography (PET) imaging of HER2 expression could potentially be used to select patients for HER2-targed therapy, predict response based on uptake and be used for monitoring. In this phase I/II study the HER2-binding Affibody molecule ABY-025 was labeled with (68)Ga-gallium ([(68)Ga]ABY-025) for PET to study effect of peptide mass, test-retest variability and correlation of quantified uptake in tumors to histopathology.
  
  
  METHODS
  Sixteen women with known metastatic breast cancer and on-going treatment were included and underwent FDG PET/CT to identify viable metastases. After iv injection of 212±46 MBq [(68)Ga]ABY-025 whole-body PET was performed at 1, 2 and 4 h. In the first 10 patients (6 with HER2-positive and 4 with HER2-negative primary tumors), [(68)Ga]ABY-025 PET/CT with two different doses of injected peptide was performed one week apart. In the last six patients (5 HER2-positive and 1 HER2-negative primary tumors), repeated [(68)Ga]ABY-025 PET were performed one week apart as a test-retest of uptake in individual lesions. Biopsies from 16 metastases in 12 patients were collected for verification of HER2 expression by immunohistochemistry and in-situ hybridization.
  
  
  RESULTS
  Imaging 4h after injection with high peptide content discriminated HER2-positive metastases best (p<0.01). PET SUV correlated with biopsy HER2-scores (r=0.91, p<0.001). Uptake was five times higher in HER2-positive than in HER2-negative lesions with no overlap (p=0.005). The test-retest intra-class correlation was r=0.996. [(68)Ga]ABY-025 PET correctly identified conversion and mixed expression of HER2 and targeted treatment was changed in 3 of the 16 patients.
  
  
  CONCLUSIONS
  [(68)Ga]ABY-025 PET accurately quantifies whole-body HER2-receptor status in metastatic breast cancer.
authors.affiliation: 1. Section of Nuclear Medicine and PET, Department of Surgical Sciences, Uppsala University, Uppsala, Sweden.
authors.forename: Jens
authors.initials: J
authors.lastname: Sörensen
authors.affiliation: 1. Section of Nuclear Medicine and PET, Department of Surgical Sciences, Uppsala University, Uppsala, Sweden.
authors.forename: Irina
authors.initials: I
authors.lastname: Velikyan
authors.affiliation: 1. Section of Nuclear Medicine and PET, Department of Surgical Sciences, Uppsala University, Uppsala, Sweden.
authors.forename: Dan
authors.initials: D
authors.lastname: Sandberg
authors.affiliation: 2. Affibody AB, Solna, Sweden.
authors.forename: Anders
authors.initials: A
authors.lastname: Wennborg
authors.affiliation: 2. Affibody AB, Solna, Sweden.; 3. Department of Immunology, Genetics and Pathology, Uppsala University, Uppsala, Sweden.
authors.forename: Joachim
authors.initials: J
authors.lastname: Feldwisch
authors.affiliation: 3. Department of Immunology, Genetics and Pathology, Uppsala University, Uppsala, Sweden.
authors.forename: Vladimir
authors.initials: V
authors.lastname: Tolmachev
authors.affiliation: 4. Preclinical PET Platform, Uppsala University, Uppsala, Sweden.
authors.forename: Anna
authors.initials: A
authors.lastname: Orlova
authors.affiliation: 1. Section of Nuclear Medicine and PET, Department of Surgical Sciences, Uppsala University, Uppsala, Sweden.
authors.forename: Mattias
authors.initials: M
authors.lastname: Sandström
authors.affiliation: 1. Section of Nuclear Medicine and PET, Department of Surgical Sciences, Uppsala University, Uppsala, Sweden.
authors.forename: Mark
authors.initials: M
authors.lastname: Lubberink
authors.affiliation: 3. Department of Immunology, Genetics and Pathology, Uppsala University, Uppsala, Sweden.; 5. Department of Pathology, Uppsala University Hospital, Uppsala, Sweden.
authors.forename: Helena
authors.initials: H
authors.lastname: Olofsson
authors.affiliation: 3. Department of Immunology, Genetics and Pathology, Uppsala University, Uppsala, Sweden.
authors.forename: Jörgen
authors.initials: J
authors.lastname: Carlsson
authors.affiliation: 3. Department of Immunology, Genetics and Pathology, Uppsala University, Uppsala, Sweden.
authors.forename: Henrik
authors.initials: H
authors.lastname: Lindman
mesh_terms: D000328:Adult; D000368:Aged; D001943:Breast Neoplasms / Q000000981:diagnostic imaging* / Q000378:metabolism / Q000473:pathology; D016022:Case-Control Studies; D005260:Female; D005710:Gallium Radioisotopes; D006801:Humans; D008875:Middle Aged; D064847:Multimodal Imaging; D009362:Neoplasm Metastasis; D010446:Peptide Fragments / Q000737:chemistry / Q000493:pharmacokinetics*; D049268:Positron-Emission Tomography; D011485:Protein Binding; D019275:Radiopharmaceuticals / Q000737:chemistry / Q000493:pharmacokinetics*; D018719:Erb-b2 Receptor Tyrosine Kinases / Q000235:genetics / Q000378:metabolism*; D013205:Staphylococcal Protein A / Q000737:chemistry; D014057:Tomography, X-Ray Computed
chemical_list: D005710:Gallium Radioisotopes; D010446:Peptide Fragments; D019275:Radiopharmaceuticals; D018719:Erb-b2 Receptor Tyrosine Kinases; D013205:Staphylococcal Protein A; C000612383:68Ga-ABY-025; C549680:ABY-025; C508053:ERBB2 protein, human
keywords: 68Ga-gallium; Affibody; HER2-receptor; breast cancer metastases; clinical study