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A critical review of radiotracers in the positron emission tomography imaging of traumatic brain injury: FDG, tau, and amyloid imaging in mild traumatic brain injury and chronic traumatic encephalopathy

  • Review Article
  • Published:
European Journal of Nuclear Medicine and Molecular Imaging Aims and scope Submit manuscript

Abstract

Purpose

Positron emission tomography (PET) has been widely utilized in the study of traumatic brain injury (TBI) for decades. While most applications of PET have attempted to assess neuronal function after TBI, more recently, novel radiotracers have sought to image biomarkers in the context of TBI and chronic traumatic encephalopathy (CTE).

Methods

This review will begin with an overview of TBI and CTE along with the acute and chronic pathophysiological consequences of TBI. Next, glycolysis, beta-amyloid, and tau protein radiotracers will be critically assessed in light of the most recent imaging studies available.

Conclusions

Based on the scientific relevance of such radiotracers to the molecular processes of TBI and CTE along with the broader evidence of radiotracer specificity and selectivity, this review will weigh the strengths and weaknesses of each radiotracer. Nonetheless, the evidence indicates that PET will continue to be a powerful modality in the diagnosis of TBI-related conditions.

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Abbreviations

[11C]PBB3:

[11C]pyridinyl-butadienyl-benzothiazole 3

[11C]PiB:

2-(4′-[11C]methylaminophenyl)-6-hydroxybenzothiazole

[18F]FDDNP:

2-(1-{6-[(2-[18F]fluoroethyl)(methyl) amino]-2-naphthyl} ethylidene) malononitrile

[18F]FDG:

2-deoxy-2-(18F)fluoro-d-glucose

[18F]Florbetapir:

4-[(E)-2-[6-[2-[2-(2-(18F)fluoranylethoxy)ethoxy]ethoxy]pyridin-3-yl]ethenyl]-N-methylaniline

[18F]Flortaucipir:

7-(6-(18F)fluoranylpyridin-3-yl)-5H-pyrido[4,3-b]indole

[18F]THK-5351:

(2S)-1-(18F)fluoranyl-3-[2-[6-(methylamino)pyridin-3-yl]quinolin-6-yl]oxypropan-2-ol

AD:

Alzheimer’s disease

APOE:

epsilon4 allele-apolipoprotein E genotypes

APP:

amyloid precursor protein

Aβ:

amyloid-β

BACE:

beta-site APP cleaving enzyme

BBB:

blood–brain barrier

CBF:

cerebral blood flow

CSF:

cerebral spine fluid

CTE:

chronic traumatic encephalopathy

DAI:

diffuse axonal injury

DTI:

diffuse tensor imaging

MAO-A:

monoamine oxidase A

MAO-B:

monoamine oxidase B

Moderate TBI:

moderate traumatic brain injury

mTBI:

mild traumatic brain injury

NFT:

neurofibrillary tangles

PCS:

post concussive syndrome

PD:

Parkinson’s disease

PHF:

paired protein filaments

PVC:

partial volume correction

SD:

spreading depression

sTBI:

severe traumatic brain injury

SUV:

standardized uptake values

SUVR:

SUV ratio

TBI:

traumatic brain injury

TDP-43:

TAR DNA-binding protein 43

α-syn:

α-synuclein

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  1. Department of Radiology, Hospital of the University of Pennsylvania, 3400 Spruce St, Philadelphia, PA, 19104, USA

    Cyrus Ayubcha, Chaitanya Rojulpote, Thomas J. Werner & Abass Alavi

  2. Division for Radiology and Nuclear Medicine, Oslo University Hospital, Oslo, Norway

    Mona-Elisabeth Revheim

  3. Institute of Clinical Medicine, Faculty of Medicine, University of Oslo, Oslo, Norway

    Mona-Elisabeth Revheim

  4. Department of Integrative Medicine and Nutritional Sciences, Marcus Institute of Integrative Health, Thomas Jefferson University, Philadelphia, PA, USA

    Andrew Newberg

  5. Department of Radiology, Thomas Jefferson University, Philadelphia, PA, USA

    Andrew Newberg

  6. Department of Radiology, Massachusetts General Hospital, Boston, MA, USA

    Mateen Moghbel

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Ayubcha, C., Revheim, ME., Newberg, A. et al. A critical review of radiotracers in the positron emission tomography imaging of traumatic brain injury: FDG, tau, and amyloid imaging in mild traumatic brain injury and chronic traumatic encephalopathy. Eur J Nucl Med Mol Imaging 48, 623–641 (2021). https://doi.org/10.1007/s00259-020-04926-4

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