title: Visualization of angiogenesis during cancer development in the polyoma middle T breast cancer model: molecular imaging with (R)-[11C]PAQ.
abstract: BACKGROUND
  Vascular endothelial growth factor receptor 2 (VEGFR2) is a crucial mediator of tumour angiogenesis. High expression levels of the receptor have been correlated to poor prognosis in cancer patients. Reliable imaging biomarkers for stratifying patients for anti-angiogenic therapy could therefore be valuable for increasing treatment success rates. The aim of this study was to investigate the pharmacokinetics and angiogenesis imaging abilities of the VEGFR2-targeting positron emission tomography (PET) tracer (R)-[11C]PAQ.
  
  
  METHODS
  (R)-[11C]PAQ was evaluated in the mouse mammary tumour virus-polyoma middle T (MMTV-PyMT) model of metastatic breast cancer. Mice at different stages of disease progression were imaged with (R)-[11C]PAQ PET, and results were compared to those obtained with [18 F]FDG PET and magnetic resonance imaging. (R)-[11C]PAQ uptake levels were also compared to ex vivo immunofluorescence analysis of tumour- and angiogenesis-specific biomarkers. Additional pharmacokinetic studies were performed in rat and mouse.
  
  
  RESULTS
  A heterogeneous uptake of (R)-[11C]PAQ was observed in the tumorous mammary glands. Ex vivo analysis confirmed the co-localization of areas with high radioactivity uptake and areas with elevated levels of VEGFR2. In some animals, a high focal uptake was observed in the lungs. The lung uptake correlated to metastatic and angiogenic activity, but not to uptake of [18 F]FDG PET. The pharmacokinetic studies revealed a limited metabolism and excretion during the 1-h scan and a distribution of radioactivity mainly to the liver, kidneys and lungs. In rat, a high uptake was additionally observed in adrenal and parathyroid glands.
  
  
  CONCLUSIONS
  The results indicate that (R)-[11C]PAQ is a promising imaging biomarker for visualization of angiogenesis, based on VEGFR2 expression, in primary tumours and during metastasis development.
authors.affiliation: Department of Neuroradiology, Karolinska University Hospital, Solna, Stockholm 171 76, Sweden. erik.samen@ki.se.
authors.forename: Erik
authors.initials: E
authors.lastname: Samén
authors.forename: Li
authors.initials: L
authors.lastname: Lu
authors.forename: Jan
authors.initials: J
authors.lastname: Mulder
authors.forename: Jan-Olov
authors.initials: JO
authors.lastname: Thorell
authors.forename: Peter
authors.initials: P
authors.lastname: Damberg
authors.forename: Tetyana
authors.initials: T
authors.lastname: Tegnebratt
authors.forename: Lars
authors.initials: L
authors.lastname: Holmgren
authors.forename: Helene
authors.initials: H
authors.lastname: Rundqvist
authors.forename: Sharon
authors.initials: S
authors.lastname: Stone-Elander