Cited by 158Traumatic Brain Injury ResearchAlzheimer's disease research and treatmentsTraumatic Brain Injury and Neurovascular Disturbances

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Amyloid Imaging With Carbon 11–Labeled Pittsburgh Compound B for Traumatic Brain Injury

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Hong, Young T., Veenith, Tonny, Dewar, Deborah, Outtrim, Joanne G., Mani, Vaithianadan, Williams, Claire, Pimlott, Sally, Hutchinson, Peter J. A., Tavares, Adriana, Canales, Roberto, Mathis, Chester A., Klunk, William E., Aigbirhio, Franklin I., Coles, Jonathan P., Baron, Jean-Claude, Pickard, John D., Fryer, Tim D., Stewart, William, Menon, David K.·2014·JAMA Neurology

DOI 10.1001/jamaneurol.2013.4847PMC PMC4084932

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Abstract

OBJECTIVES: To image amyloid deposition in patients with traumatic brain injury (TBI) using carbon 11-labeled Pittsburgh Compound B ([11C]PiB) positron emission tomography (PET) and to validate these findings using tritium-labeled PiB ([3H]PiB) autoradiography and immunocytochemistry in autopsy-acquired tissue. DESIGN, SETTING, AND PARTICIPANTS: In vivo PET at tertiary neuroscience referral center and ex vivo immunocytochemistry of autopsy-acquired brain tissue from a neuropathology archive. [11C]PiB PET was used to image amyloid deposition in 11 controls (median [range] age, 35 [24-60] years) and in 15 patients (median [range] age, 33 [21-50] years) between 1 and 361 days after a TBI. [3H]PiB autoradiography and immunocytochemistry for β-amyloid (Aβ) and β-amyloid precursor protein in brain tissue were obtained from separate cohorts of 16 patients (median [range] age, 46 [21-70] years) who died between 3 hours and 56 days after a TBI and 7 controls (median [range] age, 61 [29-71] years) who died of other causes. MAIN OUTCOMES AND MEASURES: We quantified the [11C]PiB distribution volume ratio and standardized uptake value ratio in PET images. The distribution volume ratio and the standardized uptake value ratio were measured in cortical gray matter, white matter, and multiple cortical and white matter regions of interest, as well as in striatal and thalamic regions of interest. We examined [3H]PiB binding and Aβ and β-amyloid precursor protein immunocytochemistry in autopsy-acquired brain tissue. RESULTS: Compared with the controls, the patients with TBI showed significantly increased [11C]PiB distribution volume ratios in cortical gray matter and the striatum (corrected P < .05 for both), but not in the thalamus or white matter. Increases in [11C]PiB distribution volume ratios in patients with TBI were seen across most cortical subregions, were replicated using comparisons of standardized uptake value ratios, and could not be accounted for by methodological confounders. Autoradiography revealed [3H]PiB binding in neocortical gray matter, in regions where amyloid deposition was demonstrated by immunocytochemistry; white matter showed Aβ and β-amyloid precursor protein by immunocytochemistry, but no [3H]PiB binding. No plaque-associated amyloid immunoreactivity or [3H]PiB binding was seen in cerebellar gray matter in autopsy-acquired tissue from either controls or patients with TBI, although 1 sample of cerebellar tissue from a patient with TBI showed amyloid angiopathy in meningeal vessels. CONCLUSIONS AND RELEVANCE: [11C]PiB shows increased binding following TBI. The specificity of this binding is supported by neocortical [3H]PiB binding in regions of amyloid deposition in the postmortem tissue of patients with TBI. [11C]PiB PET could be valuable in imaging amyloid deposition following TBI.

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Authors: Hong, Y. T., Veenith, T., Dewar, D., Outtrim, J. G., Mani, V., Williams, C., Pimlott, S., Hutchinson, P. J. A., Tavares, A., Canales, R., Mathis, C. A., Klunk, W. E., Aigbirhio, F. I., Coles, J. P., Baron, J.-C., Pickard, J. D., Fryer, T. D., Stewart, W., & Menon, D. K.
Affiliations: University of Pittsburgh (US)
University of Glasgow and Southern General Hospital, Glasgow, Scotland
ORCID: Veenith, Tonny
Dewar, Deborah
Outtrim, Joanne G.
Williams, Claire
Pimlott, Sally
Hutchinson, Peter J. A.
Tavares, Adriana
Mathis, Chester A.
Klunk, William E.
Aigbirhio, Franklin I.
Coles, Jonathan P.
Baron, Jean-Claude
Pickard, John D.
Fryer, Tim D.
Menon, David K.
Venue: JAMA Neurology
Publisher: American Medical Association (AMA)
Published: 2014-01-01
Volume: 71
Issue: 1
Pages: 23
ISSN: 2168-6149 (ISSN-L)
DOI: 10.1001/jamaneurol.2013.4847
PMC: PMC4084932
OpenAlex: W2166402688
Cited by: 158
References: 39
Citations by year: 2026: 3 · 2025: 8 · 2024: 8 · 2023: 6 · 2022: 13 · 2021: 13 · 2020: 9 · 2019: 13 · 2018: 11 · 2017: 14 · 2016: 20 · 2015: 23 · 2014: 15
FWCI: 14.57
Type: journal article
Language: en
Open access: green
www.ncbi.nlm.nih.gov
Locations: JAMA Neurology (publishedVersion)
PubMed (publishedVersion)
Europe PMC (PubMed Central) (acceptedVersion)
PubMed Central (acceptedVersion)
Apollo (University of Cambridge) (submittedVersion)
ENLIGHTEN (Jurnal Bimbingan dan Konseling Islam) (submittedVersion)
University of Birmingham Research Portal (University of Birmingham) (submittedVersion)
Apollo
Funders: National Institute for Health and Care Research (NF-SI-0508-10327, NF-SI-0512-10090, NIHR-RP-R3-12-013)
Academy of Medical Sciences
Medical Research Council (RG46503)
NIHR Cambridge Biomedical Research Centre
National Institute on Aging (P01AG025204, RF1AG025516, P50AG005133, AG025204, R37AG025516)
Topics: Health Sciences › Medicine › Clinical Neurology › Traumatic Brain Injury Research
Life Sciences › Neuroscience › Cellular and Molecular Neuroscience › Alzheimer's disease research and treatments
Health Sciences › Medicine › Clinical Neurology › Traumatic Brain Injury and Neurovascular Disturbances
Keywords: traumatic brain injury, amyloid deposition, Pittsburgh compound B, amyloid-beta, amyloid precursor protein, immunocytochemistry, distribution volume ratio, standardized uptake value ratio, cortical gray matter, striatum, thalamus, white matter, autopsy brain tissue, neuroimaging biomarkers
MeSH terms: Adult, Aged, Aniline Compounds, Brain, Brain Injuries, Carbon Radioisotopes, Female, Humans, Male, Middle Aged, Thiazoles, Time Factors, Tritium, Cohort Studies, Amyloid beta-Peptides, Positron-Emission Tomography, Young Adult

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Amyloid Imaging With Carbon 11–Labeled Pittsburgh Compound B for Traumatic Brain Injury

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