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Evidence for astrocytosis in prodromal Alzheimer disease provided by 11C-deuterium-L-deprenyl: a multitracer PET paradigm combining 11C-Pittsburgh compound B and 18F-FDG.
J Nucl Med. 2012 Jan; 53(1):37-46.JN

Abstract

Astrocytes colocalize with fibrillar amyloid-β (Aβ) plaques in postmortem Alzheimer disease (AD) brain tissue. It is therefore of great interest to develop a PET tracer for visualizing astrocytes in vivo, enabling the study of the regional distribution of both astrocytes and fibrillar Aβ. A multitracer PET investigation was conducted for patients with mild cognitive impairment (MCI), patients with mild AD, and healthy controls using (11)C-deuterium-L-deprenyl ((11)C-DED) to measure monoamine oxidase B located in astrocytes. Along with (11)C-DED PET, (11)C-Pittsburgh compound B ((11)C-PIB; fibrillar Aβ deposition), (18)F-FDG (glucose metabolism), T1 MRI, cerebrospinal fluid, and neuropsychologic data were acquired from the patients.

METHODS

(11)C-DED PET was performed in MCI patients (n = 8; mean age ± SD, 62.6 ± 7.5 y; mean Mini Mental State Examination, 27.5 ± 2.1), AD patients (n = 7; mean age, 65.1 ± 6.3 y; mean Mini Mental State Examination, 24.4 ± 5.7), and healthy age-matched controls (n = 14; mean age, 64.7 ± 3.6 y). A modified reference Patlak model, with cerebellar gray matter as a reference, was chosen for kinetic analysis of the (11)C-DED data. (11)C-DED data from 20 to 60 min were analyzed using a digital brain atlas. Mean regional (18)F-FDG uptake and (11)C-PIB retention were calculated for each patient, with cerebellar gray matter as a reference.

RESULTS

ANOVA analysis of the regional (11)C-DED binding data revealed a significant group effect in the bilateral frontal and bilateral parietal cortices related to increased binding in the MCI patients. All patients, except 3 with MCI, showed high (11)C-PIB retention. Increased (11)C-DED binding in most cortical and subcortical regions was observed in MCI (11)C-PIB+ patients relative to controls, MCI (11)C-PIB (negative) patients, and AD patients. No regional correlations were found between the 3 PET tracers.

CONCLUSION

Increased (11)C-DED binding throughout the brain of the MCI (11)C-PIB+ patients potentially suggests that astrocytosis is an early phenomenon in AD development.

Links

Publisher Full Text (DOI)

Authors+Show Affiliations

Carter SF
Department of Neurobiology, Care Sciences and Society, Karolinska Institutet, Stockholm, Sweden.
Schöll M
No affiliation info available
Almkvist O
No affiliation info available
Wall A
No affiliation info available
Engler H
No affiliation info available
Långström B
No affiliation info available
Nordberg A
No affiliation info available

MeSH

AgedAlzheimer DiseaseAmyloid beta-PeptidesAniline CompoundsBenzothiazolesBrainCase-Control StudiesCognitive DysfunctionDeuteriumFemaleFluorodeoxyglucose F18GliosisHumansMaleMiddle AgedMonoamine OxidaseNeuropsychological TestsPositron-Emission TomographyRadioactive TracersRetrospective StudiesSelegilineThiazoles

Pub Type(s)

Journal Article
Multicenter Study
Research Support, Non-U.S. Gov't

Language

eng

PubMed ID

22213821

Citation

Carter, Stephen F., et al. "Evidence for Astrocytosis in Prodromal Alzheimer Disease Provided By 11C-deuterium-L-deprenyl: a Multitracer PET Paradigm Combining 11C-Pittsburgh Compound B and 18F-FDG." Journal of Nuclear Medicine : Official Publication, Society of Nuclear Medicine, vol. 53, no. 1, 2012, pp. 37-46.
Carter SF, Schöll M, Almkvist O, et al. Evidence for astrocytosis in prodromal Alzheimer disease provided by 11C-deuterium-L-deprenyl: a multitracer PET paradigm combining 11C-Pittsburgh compound B and 18F-FDG. J Nucl Med. 2012;53(1):37-46.
Carter, S. F., Schöll, M., Almkvist, O., Wall, A., Engler, H., Långström, B., & Nordberg, A. (2012). Evidence for astrocytosis in prodromal Alzheimer disease provided by 11C-deuterium-L-deprenyl: a multitracer PET paradigm combining 11C-Pittsburgh compound B and 18F-FDG. Journal of Nuclear Medicine : Official Publication, Society of Nuclear Medicine, 53(1), 37-46. https://doi.org/10.2967/jnumed.110.087031
Carter SF, et al. Evidence for Astrocytosis in Prodromal Alzheimer Disease Provided By 11C-deuterium-L-deprenyl: a Multitracer PET Paradigm Combining 11C-Pittsburgh Compound B and 18F-FDG. J Nucl Med. 2012;53(1):37-46. PubMed PMID: 22213821.
* Article titles in AMA citation format should be in sentence-case
TY - JOUR T1 - Evidence for astrocytosis in prodromal Alzheimer disease provided by 11C-deuterium-L-deprenyl: a multitracer PET paradigm combining 11C-Pittsburgh compound B and 18F-FDG. AU - Carter,Stephen F, AU - Schöll,Michael, AU - Almkvist,Ove, AU - Wall,Anders, AU - Engler,Henry, AU - Långström,Bengt, AU - Nordberg,Agneta, PY - 2012/1/4/entrez PY - 2012/1/4/pubmed PY - 2012/3/1/medline SP - 37 EP - 46 JF - Journal of nuclear medicine : official publication, Society of Nuclear Medicine JO - J Nucl Med VL - 53 IS - 1 N2 - UNLABELLED: Astrocytes colocalize with fibrillar amyloid-β (Aβ) plaques in postmortem Alzheimer disease (AD) brain tissue. It is therefore of great interest to develop a PET tracer for visualizing astrocytes in vivo, enabling the study of the regional distribution of both astrocytes and fibrillar Aβ. A multitracer PET investigation was conducted for patients with mild cognitive impairment (MCI), patients with mild AD, and healthy controls using (11)C-deuterium-L-deprenyl ((11)C-DED) to measure monoamine oxidase B located in astrocytes. Along with (11)C-DED PET, (11)C-Pittsburgh compound B ((11)C-PIB; fibrillar Aβ deposition), (18)F-FDG (glucose metabolism), T1 MRI, cerebrospinal fluid, and neuropsychologic data were acquired from the patients. METHODS: (11)C-DED PET was performed in MCI patients (n = 8; mean age ± SD, 62.6 ± 7.5 y; mean Mini Mental State Examination, 27.5 ± 2.1), AD patients (n = 7; mean age, 65.1 ± 6.3 y; mean Mini Mental State Examination, 24.4 ± 5.7), and healthy age-matched controls (n = 14; mean age, 64.7 ± 3.6 y). A modified reference Patlak model, with cerebellar gray matter as a reference, was chosen for kinetic analysis of the (11)C-DED data. (11)C-DED data from 20 to 60 min were analyzed using a digital brain atlas. Mean regional (18)F-FDG uptake and (11)C-PIB retention were calculated for each patient, with cerebellar gray matter as a reference. RESULTS: ANOVA analysis of the regional (11)C-DED binding data revealed a significant group effect in the bilateral frontal and bilateral parietal cortices related to increased binding in the MCI patients. All patients, except 3 with MCI, showed high (11)C-PIB retention. Increased (11)C-DED binding in most cortical and subcortical regions was observed in MCI (11)C-PIB+ patients relative to controls, MCI (11)C-PIB (negative) patients, and AD patients. No regional correlations were found between the 3 PET tracers. CONCLUSION: Increased (11)C-DED binding throughout the brain of the MCI (11)C-PIB+ patients potentially suggests that astrocytosis is an early phenomenon in AD development. SN - 1535-5667 UR - https://www.unboundmedicine.com/medline/citation/22213821/Evidence_for_astrocytosis_in_prodromal_Alzheimer_disease_provided_by_11C_deuterium_L_deprenyl:_a_multitracer_PET_paradigm_combining_11C_Pittsburgh_compound_B_and_18F_FDG_ DB - PRIME DP - Unbound Medicine ER -