In vivo [11C]flumazenil-PET correlates with ex vivo [3H]flumazenil autoradiography in hippocampal sclerosis

M J Koepp, K S Hand, C Labbé, M P Richardson, W Van Paesschen, V H Baird, V J Cunningham, N G Bowery, D J Brooks, Jackie Duncan

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Abstract

By using [11C]flumazenil-positron emission tomography ([11C]FMZ-PET), we have previously shown that reductions of central benzodiazepine receptors (cBZRs) are restricted to the hippocampus in mesial temporal lobe epilepsy (mTLE) caused by unilateral hippocampal sclerosis (HS). Receptor autoradiographic studies on resected hippocampal specimens from the same patients demonstrated loss of cBZRs that was over and above loss of neurons in the CA1 subregion. Here, we report the first direct comparison of in vivo cBZR binding with [11C]FMZ-PET and ex vivo binding using [3H]FMZ autoradiography. We applied a magnetic resonance imaging-based method for partial volume effect correction to the PET images of [11C]FMZ volume of distribution ([11C]FMZ Vd) obtained in 10 patients with refractory mTLE due to unilateral, histologically verified HS. Saturation autoradiography was performed on the hippocampal specimens obtained from the same patients, allowing calculation of receptor availability ([3H]FMZ Bmax). After correction for partial volume effect, [11C]FMZ Vd in the body of the epileptogenic hippocampus was reduced by a mean of 42.1% compared with normal controls. [3H]FMZ Bmax, determined autoradiographically from the same hippocampal tissue, was reduced by a mean of 42.7% compared with control hippocampi. Absolute in vivo and ex vivo measurements of cBZR binding for the body of the hippocampus were significantly correlated in each individual. Our study demonstrates that reduction of available cBZR on remaining neurons in HS can be reliably detected in vivo by using [11C]FMZ-PET after correction for partial volume effect.
Original languageEnglish
Pages (from-to)618-26
Number of pages9
JournalAnnals of Neurology
Volume43
Issue number5
DOIs
Publication statusPublished - 1998

Fingerprint

Flumazenil
Sclerosis
GABA-A Receptors
Autoradiography
Hippocampus
Temporal Lobe Epilepsy
Neurons
Positron-Emission Tomography
Magnetic Resonance Imaging

Keywords

  • Adult
  • Autoradiography
  • Carbon Radioisotopes
  • Electroencephalography
  • Epilepsy, Temporal Lobe
  • Female
  • Flumazenil
  • Hippocampus
  • Humans
  • Male
  • Middle Aged
  • Neocortex
  • Sclerosis
  • Tomography, Emission-Computed
  • Tritium

Cite this

Koepp, M. J., Hand, K. S., Labbé, C., Richardson, M. P., Van Paesschen, W., Baird, V. H., ... Duncan, J. (1998). In vivo [11C]flumazenil-PET correlates with ex vivo [3H]flumazenil autoradiography in hippocampal sclerosis. Annals of Neurology, 43(5), 618-26. https://doi.org/10.1002/ana.410430510

In vivo [11C]flumazenil-PET correlates with ex vivo [3H]flumazenil autoradiography in hippocampal sclerosis. / Koepp, M J; Hand, K S; Labbé, C; Richardson, M P; Van Paesschen, W; Baird, V H; Cunningham, V J; Bowery, N G; Brooks, D J; Duncan, Jackie.

In: Annals of Neurology, Vol. 43, No. 5, 1998, p. 618-26.

Research output: Contribution to journalArticle

Koepp, MJ, Hand, KS, Labbé, C, Richardson, MP, Van Paesschen, W, Baird, VH, Cunningham, VJ, Bowery, NG, Brooks, DJ & Duncan, J 1998, 'In vivo [11C]flumazenil-PET correlates with ex vivo [3H]flumazenil autoradiography in hippocampal sclerosis', Annals of Neurology, vol. 43, no. 5, pp. 618-26. https://doi.org/10.1002/ana.410430510
Koepp, M J ; Hand, K S ; Labbé, C ; Richardson, M P ; Van Paesschen, W ; Baird, V H ; Cunningham, V J ; Bowery, N G ; Brooks, D J ; Duncan, Jackie. / In vivo [11C]flumazenil-PET correlates with ex vivo [3H]flumazenil autoradiography in hippocampal sclerosis. In: Annals of Neurology. 1998 ; Vol. 43, No. 5. pp. 618-26.
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abstract = "By using [11C]flumazenil-positron emission tomography ([11C]FMZ-PET), we have previously shown that reductions of central benzodiazepine receptors (cBZRs) are restricted to the hippocampus in mesial temporal lobe epilepsy (mTLE) caused by unilateral hippocampal sclerosis (HS). Receptor autoradiographic studies on resected hippocampal specimens from the same patients demonstrated loss of cBZRs that was over and above loss of neurons in the CA1 subregion. Here, we report the first direct comparison of in vivo cBZR binding with [11C]FMZ-PET and ex vivo binding using [3H]FMZ autoradiography. We applied a magnetic resonance imaging-based method for partial volume effect correction to the PET images of [11C]FMZ volume of distribution ([11C]FMZ Vd) obtained in 10 patients with refractory mTLE due to unilateral, histologically verified HS. Saturation autoradiography was performed on the hippocampal specimens obtained from the same patients, allowing calculation of receptor availability ([3H]FMZ Bmax). After correction for partial volume effect, [11C]FMZ Vd in the body of the epileptogenic hippocampus was reduced by a mean of 42.1{\%} compared with normal controls. [3H]FMZ Bmax, determined autoradiographically from the same hippocampal tissue, was reduced by a mean of 42.7{\%} compared with control hippocampi. Absolute in vivo and ex vivo measurements of cBZR binding for the body of the hippocampus were significantly correlated in each individual. Our study demonstrates that reduction of available cBZR on remaining neurons in HS can be reliably detected in vivo by using [11C]FMZ-PET after correction for partial volume effect.",
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AU - Koepp, M J

AU - Hand, K S

AU - Labbé, C

AU - Richardson, M P

AU - Van Paesschen, W

AU - Baird, V H

AU - Cunningham, V J

AU - Bowery, N G

AU - Brooks, D J

AU - Duncan, Jackie

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N2 - By using [11C]flumazenil-positron emission tomography ([11C]FMZ-PET), we have previously shown that reductions of central benzodiazepine receptors (cBZRs) are restricted to the hippocampus in mesial temporal lobe epilepsy (mTLE) caused by unilateral hippocampal sclerosis (HS). Receptor autoradiographic studies on resected hippocampal specimens from the same patients demonstrated loss of cBZRs that was over and above loss of neurons in the CA1 subregion. Here, we report the first direct comparison of in vivo cBZR binding with [11C]FMZ-PET and ex vivo binding using [3H]FMZ autoradiography. We applied a magnetic resonance imaging-based method for partial volume effect correction to the PET images of [11C]FMZ volume of distribution ([11C]FMZ Vd) obtained in 10 patients with refractory mTLE due to unilateral, histologically verified HS. Saturation autoradiography was performed on the hippocampal specimens obtained from the same patients, allowing calculation of receptor availability ([3H]FMZ Bmax). After correction for partial volume effect, [11C]FMZ Vd in the body of the epileptogenic hippocampus was reduced by a mean of 42.1% compared with normal controls. [3H]FMZ Bmax, determined autoradiographically from the same hippocampal tissue, was reduced by a mean of 42.7% compared with control hippocampi. Absolute in vivo and ex vivo measurements of cBZR binding for the body of the hippocampus were significantly correlated in each individual. Our study demonstrates that reduction of available cBZR on remaining neurons in HS can be reliably detected in vivo by using [11C]FMZ-PET after correction for partial volume effect.

AB - By using [11C]flumazenil-positron emission tomography ([11C]FMZ-PET), we have previously shown that reductions of central benzodiazepine receptors (cBZRs) are restricted to the hippocampus in mesial temporal lobe epilepsy (mTLE) caused by unilateral hippocampal sclerosis (HS). Receptor autoradiographic studies on resected hippocampal specimens from the same patients demonstrated loss of cBZRs that was over and above loss of neurons in the CA1 subregion. Here, we report the first direct comparison of in vivo cBZR binding with [11C]FMZ-PET and ex vivo binding using [3H]FMZ autoradiography. We applied a magnetic resonance imaging-based method for partial volume effect correction to the PET images of [11C]FMZ volume of distribution ([11C]FMZ Vd) obtained in 10 patients with refractory mTLE due to unilateral, histologically verified HS. Saturation autoradiography was performed on the hippocampal specimens obtained from the same patients, allowing calculation of receptor availability ([3H]FMZ Bmax). After correction for partial volume effect, [11C]FMZ Vd in the body of the epileptogenic hippocampus was reduced by a mean of 42.1% compared with normal controls. [3H]FMZ Bmax, determined autoradiographically from the same hippocampal tissue, was reduced by a mean of 42.7% compared with control hippocampi. Absolute in vivo and ex vivo measurements of cBZR binding for the body of the hippocampus were significantly correlated in each individual. Our study demonstrates that reduction of available cBZR on remaining neurons in HS can be reliably detected in vivo by using [11C]FMZ-PET after correction for partial volume effect.

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KW - Carbon Radioisotopes

KW - Electroencephalography

KW - Epilepsy, Temporal Lobe

KW - Female

KW - Flumazenil

KW - Hippocampus

KW - Humans

KW - Male

KW - Middle Aged

KW - Neocortex

KW - Sclerosis

KW - Tomography, Emission-Computed

KW - Tritium

U2 - 10.1002/ana.410430510

DO - 10.1002/ana.410430510

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VL - 43

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JO - Annals of Neurology

JF - Annals of Neurology

SN - 0364-5134

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