title: 68Ga-DOTA-affibody molecule for in vivo assessment of HER2/neu expression with PET.
abstract: OBJECTIVE
  Overexpression of HER2/neu in breast cancer is correlated with a poor prognosis. It may vary between primary tumors and metastatic lesions and change during the treatment. Therefore, there is a need for a new means to assess HER2/neu expression in vivo. In this work, we used (68)Ga-labeled DOTA-Z(HER2:2891)-Affibody to monitor HER2/neu expression in a panel of breast cancer xenografts.
  
  
  METHODS
  DOTA-Z(HER2:2891)-Affibody molecules were labeled with (68)Ga. In vitro binding was characterized by a receptor saturation assay. Biodistribution and PET imaging studies were conducted in athymic nude mice bearing subcutaneous human breast cancer tumors with three different levels of HER2/neu expression. Nonspecific uptake was analyzed using non-HER2-specific Affibody molecules. Signal detected by PET was compared with ex vivo assessment of the tracer uptake and HER2/neu expression.
  
  
  RESULTS
  The (68)Ga-DOTA-Z(HER2:2891)-Affibody probe showed high binding affinity to MDA-MB-361 cells (K (D) = 1.4 ± 0.19 nM). In vivo biodistribution and PET imaging studies demonstrated high radioactivity uptake in HER2/neu-positive tumors. Tracer was eliminated quickly from the blood and normal tissues, resulting in high tumor-to-blood ratios. The highest concentration of radioactivity in normal tissue was seen in the kidneys (227 ± 14%ID/g). High-contrast PET images of HER2/neu-overexpressing tumors were recorded as soon as 1 h after tracer injection. A good correlation was observed between PET imaging, biodistribution estimates of tumor tracer concentration, and the receptor expression.
  
  
  CONCLUSIONS
  These results suggest that PET imaging using (68)Ga-DOTA-Z(HER2:2891)-Affibody is sensitive enough to detect different levels of HER2/neu expression in vivo.
authors: National Cancer Institute, National Institutes of Health, 10 Center Drive, Bethesda, MD 20892, USA.
authors: Gabriela
authors: G
authors: Kramer-Marek
authors: Nalini
authors: N
authors: Shenoy
authors: Jurgen
authors: J
authors: Seidel
authors: Gary L
authors: GL
authors: Griffiths
authors: Peter
authors: P
authors: Choyke
authors: Jacek
authors: J
authors: Capala
mesh_terms: D000818:Animals; D001943:Breast Neoplasms / Q000000981:diagnostic imaging / Q000378:metabolism / Q000473:pathology; D045744:Cell Line, Tumor; D002471:Cell Transformation, Neoplastic; D005260:Female; D005710:Gallium Radioisotopes; D015972:Gene Expression Regulation, Neoplastic; D006573:Heterocyclic Compounds, 1-Ring / Q000737:chemistry*; D006801:Humans; D051379:Mice; D064847:Multimodal Imaging; D049268:Positron-Emission Tomography / Q000379:methods*; D018719:Erb-b2 Receptor Tyrosine Kinases / Q000378:metabolism*; D011993:Recombinant Fusion Proteins / Q000097:blood / Q000737:chemistry* / Q000493:pharmacokinetics; D014057:Tomography, X-Ray Computed
chemical_list: D005710:Gallium Radioisotopes; D006573:Heterocyclic Compounds, 1-Ring; D018719:Erb-b2 Receptor Tyrosine Kinases; D011993:Recombinant Fusion Proteins; C071349:1,4,7,10-tetraazacyclododecane- 1,4,7,10-tetraacetic acid