[18F]-FMISO PET/MRI Imaging Shows Ischemic Tissue around Hematoma in Intracerebral Hemorrhage

Mol Pharm. 2020 Dec 7;17(12):4667-4675. doi: 10.1021/acs.molpharmaceut.0c00932. Epub 2020 Nov 13.

Abstract

Intracerebral hemorrhage (ICH), being the most severe cerebrovascular disease, accounts for 10-15% of all strokes. Hematoma expansion is one of the most important factors associated with poor outcome in intracerebral hemorrhage (ICH). Several studies have suggested that an "ischemic penumbra" might arise when the hematoma has a large expansion, but clinical studies are inconclusive. We performed a preclinical study to demonstrate the presence of hypoxic-ischemic tissue around the hematoma by means of longitudinal [18F]-fluoromisonidazole ([18F]-FMISO) PET/MRI studies over time in an experimental ICH model. Our results showed that all [18F]-FMISO PET/MRI images exhibited hypoxic-ischemic tissue around the hematoma area. A significant increase of [18F]-FMISO uptake was found at 18-24 h post-ICH when the maximum of hematoma volume is achieved and this increase disappeared before 42 h. These results demonstrate the presence of hypoxic tissue around the hematoma and open the possibility of new therapies aimed to reduce ischemic damage associated with ICH.

Keywords: [18F]-FMISO; hematoma; intracerebral hemorrhage; ischemic; neuroimaging.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Aged
  • Animals
  • Brain / blood supply
  • Brain / diagnostic imaging
  • Brain / pathology
  • Cerebral Hemorrhage / complications*
  • Cerebral Hemorrhage / diagnosis
  • Cerebral Hemorrhage / pathology
  • Disease Models, Animal
  • Hematoma / diagnosis*
  • Hematoma / etiology
  • Hematoma / pathology
  • Humans
  • Hypoxia-Ischemia, Brain / diagnosis*
  • Hypoxia-Ischemia, Brain / etiology
  • Hypoxia-Ischemia, Brain / pathology
  • Magnetic Resonance Imaging / methods
  • Male
  • Middle Aged
  • Misonidazole / administration & dosage
  • Misonidazole / analogs & derivatives*
  • Positron Emission Tomography Computed Tomography / methods
  • Rats
  • Stroke / etiology
  • Stroke / prevention & control*

Substances

  • fluoromisonidazole
  • Misonidazole