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Concordance between in vivo and postmortem measurements of cholinergic denervation in rats using PET with [18F]FEOBV and choline acetyltransferase immunochemistry.

Parent MJ, Cyr M, Aliaga A, Kostikov A, Schirrmacher E, Soucy JP, Mechawar N, Rosa-Neto P, Bedard MA - EJNMMI Res (2013)

Bottom Line: For both PET binding and postmortem OD, the highest losses were found in the cortical areas, with the highest reductions in the orbitofrontal, sensorimotor, and cingulate cortices.In addition, OD quantification in the affected areas accurately predicts [18F]FEOBV uptake in the same regions when regressed linearly.These findings support [18F]FEOBV as a reliable imaging agent for eventual use in human neurodegenerative conditions in which cholinergic losses are an important aspect.

View Article: PubMed Central - HTML - PubMed

Affiliation: Douglas Mental Health University Institute, McGill University, Montreal, QC H4H 1R3, Canada. maxime.parent@mail.mcgill.ca.

ABSTRACT

Background: Fluorine-18 fluoroethoxybenzovesamicol ([18F]FEOBV) is a radioligand for the selective imaging of the vesicular acetylcholine transporter with positron emission tomography (PET). The current study demonstrates that pathological cortical cholinergic deafferentation can be quantified in vivo with [18F]FEOBV PET, yielding analogous results to postmortem histological techniques.

Methods: Fifteen male rats (3 months old) underwent a cerebral infusion of 192 IgG-saporin at the level of the nucleus basalis magnocellularis. They were scanned using [18F]FEOBV PET, then sacrificed, and their brain tissues collected for immunostaining and quantification of cholinergic denervation using optical density (OD).

Results: For both PET binding and postmortem OD, the highest losses were found in the cortical areas, with the highest reductions in the orbitofrontal, sensorimotor, and cingulate cortices. In addition, OD quantification in the affected areas accurately predicts [18F]FEOBV uptake in the same regions when regressed linearly.

Conclusions: These findings support [18F]FEOBV as a reliable imaging agent for eventual use in human neurodegenerative conditions in which cholinergic losses are an important aspect.

No MeSH data available.


Related in: MedlinePlus

Anteroposterior immunocytochemistry trend. Examples of ChAT immunocytochemistry at different anteroposterior locations. The lesioned hemisphere (left column) has a distinct loss of ChAT availability when compared with the control hemisphere (right column). Note the anteroposterior trend: highest interhemispheric differences can be observed in anterior regions such as (A) the cingulate and motor cortices (AP = +2.5 mm from the bregma), (B) with smaller differences in frontal sensorimotor regions (AP = +0.2 mm from the bregma), and (C) no quantifiable effect in the parietal cortex (AP = −2.6 mm from the bregma).
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Figure 3: Anteroposterior immunocytochemistry trend. Examples of ChAT immunocytochemistry at different anteroposterior locations. The lesioned hemisphere (left column) has a distinct loss of ChAT availability when compared with the control hemisphere (right column). Note the anteroposterior trend: highest interhemispheric differences can be observed in anterior regions such as (A) the cingulate and motor cortices (AP = +2.5 mm from the bregma), (B) with smaller differences in frontal sensorimotor regions (AP = +0.2 mm from the bregma), and (C) no quantifiable effect in the parietal cortex (AP = −2.6 mm from the bregma).

Mentions: OD analyses revealed higher values in the right hemisphere (non-lesioned) with an average of 17% (t(14) = 4.98, p = 0.0002). Interhemispheric differences ranged from 0% to 40%, with higher differences being located predominantly in the frontal cortical areas, such as the cingulate, sensorimotor, and orbital cortices. Smaller losses were observed in the insular cortex, while no interhemispheric difference can be detected in the parietal regions (see Figures 2 and 3).


Concordance between in vivo and postmortem measurements of cholinergic denervation in rats using PET with [18F]FEOBV and choline acetyltransferase immunochemistry.

Parent MJ, Cyr M, Aliaga A, Kostikov A, Schirrmacher E, Soucy JP, Mechawar N, Rosa-Neto P, Bedard MA - EJNMMI Res (2013)

Anteroposterior immunocytochemistry trend. Examples of ChAT immunocytochemistry at different anteroposterior locations. The lesioned hemisphere (left column) has a distinct loss of ChAT availability when compared with the control hemisphere (right column). Note the anteroposterior trend: highest interhemispheric differences can be observed in anterior regions such as (A) the cingulate and motor cortices (AP = +2.5 mm from the bregma), (B) with smaller differences in frontal sensorimotor regions (AP = +0.2 mm from the bregma), and (C) no quantifiable effect in the parietal cortex (AP = −2.6 mm from the bregma).
© Copyright Policy - open-access
Related In: Results  -  Collection

License
Show All Figures
getmorefigures.php?uid=PMC3852759&req=5

Figure 3: Anteroposterior immunocytochemistry trend. Examples of ChAT immunocytochemistry at different anteroposterior locations. The lesioned hemisphere (left column) has a distinct loss of ChAT availability when compared with the control hemisphere (right column). Note the anteroposterior trend: highest interhemispheric differences can be observed in anterior regions such as (A) the cingulate and motor cortices (AP = +2.5 mm from the bregma), (B) with smaller differences in frontal sensorimotor regions (AP = +0.2 mm from the bregma), and (C) no quantifiable effect in the parietal cortex (AP = −2.6 mm from the bregma).
Mentions: OD analyses revealed higher values in the right hemisphere (non-lesioned) with an average of 17% (t(14) = 4.98, p = 0.0002). Interhemispheric differences ranged from 0% to 40%, with higher differences being located predominantly in the frontal cortical areas, such as the cingulate, sensorimotor, and orbital cortices. Smaller losses were observed in the insular cortex, while no interhemispheric difference can be detected in the parietal regions (see Figures 2 and 3).

Bottom Line: For both PET binding and postmortem OD, the highest losses were found in the cortical areas, with the highest reductions in the orbitofrontal, sensorimotor, and cingulate cortices.In addition, OD quantification in the affected areas accurately predicts [18F]FEOBV uptake in the same regions when regressed linearly.These findings support [18F]FEOBV as a reliable imaging agent for eventual use in human neurodegenerative conditions in which cholinergic losses are an important aspect.

View Article: PubMed Central - HTML - PubMed

Affiliation: Douglas Mental Health University Institute, McGill University, Montreal, QC H4H 1R3, Canada. maxime.parent@mail.mcgill.ca.

ABSTRACT

Background: Fluorine-18 fluoroethoxybenzovesamicol ([18F]FEOBV) is a radioligand for the selective imaging of the vesicular acetylcholine transporter with positron emission tomography (PET). The current study demonstrates that pathological cortical cholinergic deafferentation can be quantified in vivo with [18F]FEOBV PET, yielding analogous results to postmortem histological techniques.

Methods: Fifteen male rats (3 months old) underwent a cerebral infusion of 192 IgG-saporin at the level of the nucleus basalis magnocellularis. They were scanned using [18F]FEOBV PET, then sacrificed, and their brain tissues collected for immunostaining and quantification of cholinergic denervation using optical density (OD).

Results: For both PET binding and postmortem OD, the highest losses were found in the cortical areas, with the highest reductions in the orbitofrontal, sensorimotor, and cingulate cortices. In addition, OD quantification in the affected areas accurately predicts [18F]FEOBV uptake in the same regions when regressed linearly.

Conclusions: These findings support [18F]FEOBV as a reliable imaging agent for eventual use in human neurodegenerative conditions in which cholinergic losses are an important aspect.

No MeSH data available.


Related in: MedlinePlus