Amyloid imaging with carbon 11-labeled Pittsburgh compound B for traumatic brain injury.
OBJECTIVE
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.


METHODS
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.


METHODS
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
[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.
Wolfson Brain Imaging Centre, University of Cambridge, Cambridge, England5Department of Clinical Neurosciences, University of Cambridge, Cambridge, England.
Young T
YT
Hong
Division of Anaesthesia, University of Cambridge, Addenbrooke's Hospital, Cambridge, England.
Tonny
T
Veenith
Institute of Neuroscience and Psychology, University of Glasgow, Scotland.
Deborah
D
Dewar
Division of Anaesthesia, University of Cambridge, Addenbrooke's Hospital, Cambridge, England.
Joanne G
JG
Outtrim
Division of Anaesthesia, University of Cambridge, Addenbrooke's Hospital, Cambridge, England.
Vaithianadan
V
Mani
Division of Anaesthesia, University of Cambridge, Addenbrooke's Hospital, Cambridge, England.
Claire
C
Williams
University of Glasgow and Southern General Hospital, Glasgow, Scotland.
Sally
S
Pimlott
Department of Clinical Neurosciences, University of Cambridge, Cambridge, England.
Peter J A
PJ
Hutchinson
Institute of Neuroscience and Psychology, University of Glasgow, Scotland.
Adriana
A
Tavares
Wolfson Brain Imaging Centre, University of Cambridge, Cambridge, England5Department of Clinical Neurosciences, University of Cambridge, Cambridge, England.
Roberto
R
Canales
Departments of Radiology and Pharmaceutical Sciences, University of Pittsburgh, Pittsburgh, Pennsylvania.
Chester A
CA
Mathis
Departments of Psychiatry and Neurology, University of Pittsburgh School of Medicine, Pittsburgh, Pennsylvania.
William E
WE
Klunk
Wolfson Brain Imaging Centre, University of Cambridge, Cambridge, England5Department of Clinical Neurosciences, University of Cambridge, Cambridge, England.
Franklin I
FI
Aigbirhio
Division of Anaesthesia, University of Cambridge, Addenbrooke's Hospital, Cambridge, England.
Jonathan P
JP
Coles
Wolfson Brain Imaging Centre, University of Cambridge, Cambridge, England5Department of Clinical Neurosciences, University of Cambridge, Cambridge, England8INSERM U894, Université Paris Descartes, Sorbonne Paris Cité, Paris, France.
Jean-Claude
JC
Baron
Wolfson Brain Imaging Centre, University of Cambridge, Cambridge, England5Department of Clinical Neurosciences, University of Cambridge, Cambridge, England.
John D
JD
Pickard
Wolfson Brain Imaging Centre, University of Cambridge, Cambridge, England5Department of Clinical Neurosciences, University of Cambridge, Cambridge, England.
Tim D
TD
Fryer
University of Glasgow and Southern General Hospital, Glasgow, Scotland.
William
W
Stewart
Wolfson Brain Imaging Centre, University of Cambridge, Cambridge, England2Division of Anaesthesia, University of Cambridge, Addenbrooke's Hospital, Cambridge, England.
David K
DK
Menon
D000328:Adult; D000368:Aged; D016229:Amyloid beta-Peptides / Q000378:metabolism*; D000814:Aniline Compounds; D001921:Brain / Q000000981:diagnostic imaging / Q000378:metabolism* / Q000473:pathology; D001930:Brain Injuries / Q000000981:diagnostic imaging / Q000378:metabolism* / Q000473:pathology; D002250:Carbon Radioisotopes; D015331:Cohort Studies; D005260:Female; D006801:Humans; D008297:Male; D008875:Middle Aged; D049268:Positron-Emission Tomography / Q000379:methods; D013844:Thiazoles; D013997:Time Factors; D014316:Tritium; D055815:Young Adult
C475519:2-(4'-(methylamino)phenyl)-6-hydroxybenzothiazole; D016229:Amyloid beta-Peptides; D000814:Aniline Compounds; D002250:Carbon Radioisotopes; D013844:Thiazoles; D014316:Tritium