Positron emission tomography of cerebral angiogenesis and TSPO expression in a mouse model of chronic hypoxia

• Published in: Journal of cerebral blood flow and metabolism Vol. 38; no. 4; pp. 687 - 696
• Main Authors: Kanno, Iwao, Seki, Chie, Takuwa, Hiroyuki, Jin, Zhao-Hui, Boturyn, Didier, Dumy, Pascal, Furukawa, Takako, Saga, Tsuneo, Ito, Hiroshi, Masamoto, Kazuto
• Format: Journal Article
• Language: English
• Published: London, England SAGE Publications 01.04.2018; Nature Publishing Group
• Subjects: Analytical chemistry; Animals; Cerebrovascular Circulation - genetics; Chemical Sciences; Coordination Complexes; Hypoxia, Brain - diagnostic imaging; Hypoxia, Brain - metabolism; Integrin beta3 - metabolism; Isoquinolines; Male; Mice; Mice, Inbred C57BL; Neovascularization, Physiologic - physiology; Original; Peptides, Cyclic; Positron-Emission Tomography; Radiopharmaceuticals; Receptors, GABA - biosynthesis; Receptors, GABA - genetics; Angiogenesis; chronic hypoxia; translocator protein; positron emission tomography; vascular remodeling
• ISSN: 0271-678X; 1559-7016
• DOI: 10.1177/0271678X16689800

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 αVβ3 integrin and was imaged with PET. The PET imaging results showed little uptake during all of the hypoxic periods. Immunofluorescence staining of the β3 integrin, 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 of 11C-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.