Dynamic TSPO-PET for assessing early effects of cerebral hypoxia and resuscitation in new born pigs

Charlotte de Lange; Rønnaug Solberg; Jon Erik Holtedahl; Andreas Tulipan; Jon Barlinn; William Trigg; Torild Wickstrøm; Ola Didrik Saugstad; Eirik Malinen; Mona Elisabeth Revheim

doi:10.1016/j.nucmedbio.2018.08.004

Dynamic TSPO-PET for assessing early effects of cerebral hypoxia and resuscitation in new born pigs

Nucl Med Biol. 2018 Nov:66:49-57. doi: 10.1016/j.nucmedbio.2018.08.004. Epub 2018 Aug 24.

Authors

Affiliations

¹ Div. of Radiology and Nuclear Medicine, Oslo University Hospital, PO box 4950, Nydalen, N-0424 Oslo, Norway. Electronic address: charlotte.delange@medisin.uio.no.
² Dept. of Paediatric Research, Oslo University Hospital, PO box 4950, Nydalen, N-0424 Oslo, Norway; Dept. of Pediatrics, Vestfold Hospital Trust, Tønsberg, Norway.
³ Dept. of Medical Physics, Oslo University Hospital, PO box 4950, Nydalen, N-0424 Oslo, Norway.
⁴ Div. of Radiology and Nuclear Medicine, Oslo University Hospital, PO box 4950, Nydalen, N-0424 Oslo, Norway.
⁵ Dept. of Pediatrics, Oslo University Hospital, PO box 4950, Nydalen, N-0424 Oslo, Norway.
⁶ GE Healthcare, Nycoveien 1, 0401 Oslo, Norway.
⁷ Dept. of Paediatric Research, Oslo University Hospital, PO box 4950, Nydalen, N-0424 Oslo, Norway; Faculty of Medicine, University of Oslo, PO Box1078, Blindern, N-0316 Oslo, Norway.
⁸ Dept. of Medical Physics, Oslo University Hospital, PO box 4950, Nydalen, N-0424 Oslo, Norway; Dept. of Physics, University of Oslo, P.O Box 1048, Blindern, N-0316 Oslo, Norway.
⁹ Div. of Radiology and Nuclear Medicine, Oslo University Hospital, PO box 4950, Nydalen, N-0424 Oslo, Norway; Faculty of Medicine, University of Oslo, PO Box1078, Blindern, N-0316 Oslo, Norway.

PMID: 30257223
DOI: 10.1016/j.nucmedbio.2018.08.004

Abstract

Introduction: Inflammation associated with microglial activation may be an early prognostic indicator of perinatal hypoxic ischemic injury, where translocator protein (TSPO) is a known inflammatory biomarker. This piglet study used dynamic TSPO-PET with [¹⁸F]GE180 to evaluate if microglial activation after global perinatal hypoxic injury could be detected.

Methods: New born anesthetized pigs (n = 14) underwent hypoxia with fraction of inspired oxygen (FiO₂)0.08 until base excess -20 mmol/L and/or a mean arterial blood pressure decrease to 20 mm Hg, followed by resuscitation with FiO₂ 0.21 or 1.0. Three piglets served as controls and one had intracranial injection of lipopolysaccharide (LPS). Whole body [¹⁸F]GE180 Positron emission tomography-computed tomography (PET-CT) was performed repeatedly up to 32 h after hypoxia and resuscitation. Volumes of interest were traced in the basal ganglia, cerebellum and liver using MRI as anatomic correlation. Standardized uptake values (SUVs) were measured at baseline and four time-points, quantifying microglial activity over time. Statistical analysis used Mann Whitney- and Wilcoxon rank test with significance value set to p < 0.05.

Results: At baseline (n = 5), mean SUVs ±1 standard deviation were 0.43 ± 0.10 and 1.71 ± 0.62 in brain and liver respectively without significant increase after hypoxia at the four time-points (n = 5-13/time point). Succeeding LPS injection, SUV increased 80% from baseline values.

Conclusions: Cerebral inflammatory response caused by severe asphyxia was not possible to detect with [¹⁸F]GE180 PET CT the first 32 h after hypoxia and only sparse hepatic uptake was revealed.

Advances in knowledge: Early microglial activation as indicator of perinatal hypoxic ischemic injury was not detectable by TSPO-PET with [¹⁸F]GE180.

Implications for patient care: TSPO-PET with [¹⁸F]GE180 might not be suitable for early detection of perinatal hypoxic ischemic brain injury.

Keywords: Microglia activation; PET; Perinatal hypoxia ischemia; Piglet; TSPO; [(18)F]GE180.

Publication types

Research Support, Non-U.S. Gov't

MeSH terms

Animals
Animals, Newborn
Hypoxia, Brain*
Positron-Emission Tomography*
Receptors, GABA / metabolism*
Resuscitation*
Swine

Substances

Receptors, GABA