title: PET of HER2-positive pulmonary metastases with 18F-ZHER2:342 affibody in a murine model of breast cancer: comparison with 18F-FDG.
abstract: Targeted therapies often depend on the expression of the target present in the tumor. This expression can be difficult to ascertain in widespread metastases. (18)F-FDG PET/CT, although sensitive, is nonspecific for particular tumor markers. Here, we compare the use of a human epidermal growth factor receptor 2 (HER2)-specific (18)F-Z(HER2)(:342)-Affibody and (18)F-FDG in HER2-expressing pulmonary metastases in a murine model of breast cancer.
  
  
  METHODS
  The lung metastasis model was established by intravenous injection of MDA-MB-231(HER2)-Luc human breast cancer cells into the tail vein. Bioluminescence imaging was used to evaluate metastasis progression. Uptake of (18)F-Z(HER2)(:342)-Affibody and (18)F-FDG was confirmed by coregistration of the PET images with MR and CT images. At the end of the study, the presence of neoplastic cells and HER2 expression in lung tissues, and distribution of the tracer, were assessed ex vivo by immunohistochemistry and autoradiography.
  
  
  RESULTS
  (18)F-Z(HER2)(:342)-Affibody successfully targeted HER2-positive lesions in the lung and allowed detection of metastases as early as 9 wk after injection of cells. In contrast, (18)F-FDG uptake was often masked by surrounding inflammatory changes and was nonspecific for HER2 expression. HER2 expression at a cellular level correlated well with tracer uptake on autoradiography.
  
  
  CONCLUSIONS
  (18)F-Z(HER2)(:342)-Affibody is a promising tracer for evaluation of HER2 status of breast cancer metastases and is more specific for detecting HER2-positive lesions than (18)F-FDG.
authors.affiliation: Radiation Oncology Branch, National Cancer Institute, National Institutes of Health, Bethesda, Maryland, USA. gkramerm@iupui.edu
authors.forename: Gabriela
authors.initials: G
authors.lastname: Kramer-Marek
authors.forename: Marcelino
authors.initials: M
authors.lastname: Bernardo
authors.forename: Dale O
authors.initials: DO
authors.lastname: Kiesewetter
authors.forename: Ulas
authors.initials: U
authors.lastname: Bagci
authors.forename: Monika
authors.initials: M
authors.lastname: Kuban
authors.forename: Omer
authors.initials: O
authors.lastname: Aras
authors.forename: Aras
authors.initials: A
authors.lastname: Omer
authors.forename: Rafal
authors.initials: R
authors.lastname: Zielinski
authors.forename: Jurgen
authors.initials: J
authors.lastname: Seidel
authors.forename: Peter
authors.initials: P
authors.lastname: Choyke
authors.forename: Jacek
authors.initials: J
authors.lastname: Capala
mesh_terms: D000818:Animals; D045744:Cell Line, Tumor; D004195:Disease Models, Animal; D005462:Fluorine Radioisotopes; D019788:Fluorodeoxyglucose F18; D006801:Humans; D008175:Lung Neoplasms / Q000000981:diagnostic imaging* / Q000556:secondary*; D008325:Mammary Neoplasms, Experimental / Q000473:pathology*; D051379:Mice; D049268:Positron-Emission Tomography / Q000379:methods*; D019275:Radiopharmaceuticals; D018719:Erb-b2 Receptor Tyrosine Kinases / Q000032:analysis*; D011993:Recombinant Fusion Proteins
chemical_list: D005462:Fluorine Radioisotopes; D019788:Fluorodeoxyglucose F18; D019275:Radiopharmaceuticals; D018719:Erb-b2 Receptor Tyrosine Kinases; D011993:Recombinant Fusion Proteins; C515865:Z(HER2.4)2 affibody; C508053:ERBB2 protein, human