PET imaging of stroke-induced neuroinflammation in mice using [18F]PBR06

Mol Imaging Biol. 2014 Feb;16(1):109-17. doi: 10.1007/s11307-013-0664-5. Epub 2013 Jul 9.

Abstract

Purpose: The purpose of this study is to evaluate the 18 kDa translocator protein (TSPO) radioligand [(18)F]N-fluoroacetyl-N-(2,5-dimethoxybenzyl)-2-phenoxyaniline ([(18)F]PBR06) as a positron emission tomography (PET) imaging biomarker of stroke-induced neuroinflammation in a rodent model.

Procedures: Stroke was induced by transient middle cerebral artery occlusion in Balb/c mice. Dynamic PET/CT imaging with displacement and preblocking using PK111195 was performed 3 days later. PET data were correlated with immunohistochemistry (IHC) for the activated microglial markers TSPO and CD68 and with autoradiography.

Results: [(18)F]PBR06 accumulation peaked within the first 5 min postinjection, then decreased gradually, remaining significantly higher in infarct compared to noninfarct regions. Displacement or preblocking with PK11195 eliminated the difference in [(18)F]PBR06 uptake between infarct and noninfarct regions. Autoradiography and IHC correlated well spatially with uptake on PET.

Conclusions: [(18)F]PBR06 PET specifically images TSPO in microglial neuroinflammation in a mouse model of stroke and shows promise for imaging and monitoring microglial activation/neuroinflammation in other disease models.

Publication types

  • Research Support, N.I.H., Extramural
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Acetanilides*
  • Animals
  • Antigens, CD / metabolism
  • Antigens, Differentiation, Myelomonocytic / metabolism
  • Autoradiography
  • Female
  • Immunohistochemistry
  • Inflammation / diagnostic imaging*
  • Inflammation / etiology
  • Inflammation / pathology
  • Isoquinolines
  • Magnetic Resonance Imaging
  • Mice
  • Mice, Inbred BALB C
  • Nervous System / diagnostic imaging*
  • Nervous System / pathology
  • Positron-Emission Tomography*
  • Radiography
  • Stroke / complications
  • Stroke / diagnostic imaging*

Substances

  • Acetanilides
  • Antigens, CD
  • Antigens, Differentiation, Myelomonocytic
  • CD68 antigen, human
  • Isoquinolines
  • N-fluoroacetyl-N-(2,5-dimethoxybenzyl)-2-phenoxyaniline
  • PK 11195