title: Positron emission tomography of cerebral angiogenesis and TSPO expression in a mouse model of chronic hypoxia.
abstract: The present study aimed to examine whether positron emission tomography (PET) could evaluate cerebral angiogenesis. Mice were housed in a hypoxic chamber with 8-9% oxygen for 4, 7, and 14 days, and the angiogenic responses were evaluated with a radiotracer,64Cu-cyclam-RAFT-c(-RGDfK-)4, which targeted αVβ3integrin and was imaged with PET. The PET imaging results showed little uptake during all of the hypoxic periods. Immunofluorescence staining of the β3integrin, CD61, revealed weak expression, while the microvessel density assessed by CD31 staining increased with the hypoxic duration. These observations suggest that the increased vascular density originated from other types of vascular remodeling, unlike angiogenic sprouting. We then searched for any signs of vascular remodeling that could be detected using PET. PET imaging of11C-PK11195, a marker of the 18-kDa translocator protein (TSPO), revealed a transient increase at day 4 of hypoxia. Because the immunofluorescence of glial markers showed unchanged staining over the early phase of hypoxia, the observed upregulation of TSPO expression probably originated from non-glial cells (e.g. vascular cells). In conclusion, a transient increase in TSPO probe uptake was detected with PET at only the early phase of hypoxia, which indicates an early sign of vascular remodeling induced by hypoxia.
authors.affiliation: 1 Molecular Imaging Center, National Institute of Radiological Sciences, Chiba, Japan.
authors.forename: Iwao
authors.initials: I
authors.lastname: Kanno
authors.affiliation: 1 Molecular Imaging Center, National Institute of Radiological Sciences, Chiba, Japan.
authors.forename: Chie
authors.initials: C
authors.lastname: Seki
authors.affiliation: 1 Molecular Imaging Center, National Institute of Radiological Sciences, Chiba, Japan.
authors.forename: Hiroyuki
authors.initials: H
authors.lastname: Takuwa
authors.affiliation: 1 Molecular Imaging Center, National Institute of Radiological Sciences, Chiba, Japan.
authors.forename: Zhao-Hui
authors.initials: ZH
authors.lastname: Jin
authors.affiliation: 2 Département de Chimie Moléculaire, Université Grenoble Alpes, Grenoble, France.
authors.forename: Didier
authors.initials: D
authors.lastname: Boturyn
authors.affiliation: 3 Institut des Biomolécules Max Mousseron, École Nationale Supérieure de Chimie de Montpellier, Montpellier, France.
authors.forename: Pascal
authors.initials: P
authors.lastname: Dumy
authors.affiliation: 1 Molecular Imaging Center, National Institute of Radiological Sciences, Chiba, Japan.
authors.forename: Takako
authors.initials: T
authors.lastname: Furukawa
authors.affiliation: 1 Molecular Imaging Center, National Institute of Radiological Sciences, Chiba, Japan.
authors.forename: Tsuneo
authors.initials: T
authors.lastname: Saga
authors.affiliation: 1 Molecular Imaging Center, National Institute of Radiological Sciences, Chiba, Japan.
authors.forename: Hiroshi
authors.initials: H
authors.lastname: Ito
authors.affiliation: 1 Molecular Imaging Center, National Institute of Radiological Sciences, Chiba, Japan.|4 Brain Science Inspired Life Support Research Center, University of Electro-Communications, Tokyo, Japan.
authors.forename: Kazuto
authors.initials: K
authors.lastname: Masamoto
mesh_terms: D000818:Animals; D002560:Cerebrovascular Circulation / Q000235:genetics; D056831:Coordination Complexes; D002534:Hypoxia, Brain / Q000000981:diagnostic imaging* / Q000378:metabolism*; D039661:Integrin beta3 / Q000378:metabolism; D007546:Isoquinolines; D008297:Male; D051379:Mice; D008810:Mice, Inbred C57BL; D018919:Neovascularization, Physiologic / Q000502:physiology*; D010456:Peptides, Cyclic; D049268:Positron-Emission Tomography; D019275:Radiopharmaceuticals; D018079:Receptors, GABA / Q000096:biosynthesis / Q000235:genetics*
chemical_list: C560405:64Cu-cyclam-RAFT-cyclo(arginyl-glycyl-aspartyl-phenylalanyl-lysyl)4; C463819:Bzrp protein, mouse; D056831:Coordination Complexes; D039661:Integrin beta3; D007546:Isoquinolines; D010456:Peptides, Cyclic; D019275:Radiopharmaceuticals; D018079:Receptors, GABA; C037850:PK 11195
keywords: Angiogenesis; chronic hypoxia; positron emission tomography; translocator protein; vascular remodeling