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Relationship of cerebrospinal fluid markers to 11C-PiB and 18F-FDDNP binding.
J Nucl Med. 2009 Sep; 50(9):1464-70.JN

Abstract

The purpose of this study was to investigate the potential relationships between cerebrospinal fluid (CSF) measurements of beta-amyloid-1-42 (Abeta(1-42)) and total tau to (11)C-Pittsburgh compound B ((11)C-PiB) and 2-(1-{6-[(2-(18)F-fluoroethyl)(methyl)amino]-2-naphthyl}ethylidene) malononitrile ((18)F-FDDNP) binding as measured using PET.

METHODS

A total of 37 subjects were included, consisting of 15 patients with Alzheimer disease (AD), 12 patients with mild cognitive impairment, and 10 healthy controls. All subjects underwent a lumbar puncture and PET using both (11)C-PiB and (18)F-FDDNP. For both PET tracers, parametric images of binding potential were generated. Potential associations of CSF levels of Abeta(1-42) and tau with (11)C-PiB and (18)F-FDDNP binding were assessed using Pearson correlation coefficients and linear regression analyses.

RESULTS

For both global (11)C-PiB and (18)F-FDDNP binding, significant correlations with CSF levels of Abeta(1-42) (r = -0.72 and -0.37, respectively) and tau (r = 0.58 and 0.56, respectively) were found across groups (all P < 0.001, except P < 0.05 for correlation between (18)F-FDDNP and Abeta(1-42)). Linear regression analyses showed that, adjusted for regional volume, age, sex, and diagnosis, global (11)C-PiB uptake had an inverse association with Abeta(1-42) CSF levels (standardized beta = -0.50, P < 0.001), whereas there was a positive association between global (18)F-FDDNP binding and tau CSF levels (standardized beta = 0.62, P < 0.01).

CONCLUSION

The good agreement between these 2 different types of biomarkers (i.e., CSF and PET) provides converging evidence for their validity. The inverse association between (11)C-PiB and CSF tau Abeta(1-42) confirms that (11)C-PiB measures amyloid load in the brain. The positive association between (18)F-FDDNP and CSF tau suggests that at least part of the specific signal of (18)F-FDDNP in AD patients is due to tangle formation.

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Authors+Show Affiliations

Tolboom N
Departments of Nuclear Medicine and PET Research, VU University Medical Centre, Amsterdam, The Netherlands. ntolboom@vumc.nl
van der Flier WM
No affiliation info available
Yaqub M
No affiliation info available
Boellaard R
No affiliation info available
Verwey NA
No affiliation info available
Blankenstein MA
No affiliation info available
Windhorst AD
No affiliation info available
Scheltens P
No affiliation info available
Lammertsma AA
No affiliation info available
van Berckel BN
No affiliation info available

MeSH

AgedAlzheimer DiseaseAmyloid beta-PeptidesAniline CompoundsBenzothiazolesBiomarkersBrainCognition DisordersFemaleHumansMaleNitrilesPeptide FragmentsPositron-Emission TomographyProtein BindingRadiopharmaceuticalsStatistics as TopicThiazolesTissue Distributiontau Proteins

Pub Type(s)

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

Language

eng

PubMed ID

19690025

Citation

Tolboom, Nelleke, et al. "Relationship of Cerebrospinal Fluid Markers to 11C-PiB and 18F-FDDNP Binding." Journal of Nuclear Medicine : Official Publication, Society of Nuclear Medicine, vol. 50, no. 9, 2009, pp. 1464-70.
Tolboom N, van der Flier WM, Yaqub M, et al. Relationship of cerebrospinal fluid markers to 11C-PiB and 18F-FDDNP binding. J Nucl Med. 2009;50(9):1464-70.
Tolboom, N., van der Flier, W. M., Yaqub, M., Boellaard, R., Verwey, N. A., Blankenstein, M. A., Windhorst, A. D., Scheltens, P., Lammertsma, A. A., & van Berckel, B. N. (2009). Relationship of cerebrospinal fluid markers to 11C-PiB and 18F-FDDNP binding. Journal of Nuclear Medicine : Official Publication, Society of Nuclear Medicine, 50(9), 1464-70. https://doi.org/10.2967/jnumed.109.064360
Tolboom N, et al. Relationship of Cerebrospinal Fluid Markers to 11C-PiB and 18F-FDDNP Binding. J Nucl Med. 2009;50(9):1464-70. PubMed PMID: 19690025.
* Article titles in AMA citation format should be in sentence-case
TY - JOUR T1 - Relationship of cerebrospinal fluid markers to 11C-PiB and 18F-FDDNP binding. AU - Tolboom,Nelleke, AU - van der Flier,Wiesje M, AU - Yaqub,Maqsood, AU - Boellaard,Ronald, AU - Verwey,Nicolaas A, AU - Blankenstein,Marinus A, AU - Windhorst,Albert D, AU - Scheltens,Philip, AU - Lammertsma,Adriaan A, AU - van Berckel,Bart N M, Y1 - 2009/08/18/ PY - 2009/8/20/entrez PY - 2009/8/20/pubmed PY - 2009/10/23/medline SP - 1464 EP - 70 JF - Journal of nuclear medicine : official publication, Society of Nuclear Medicine JO - J Nucl Med VL - 50 IS - 9 N2 - UNLABELLED: The purpose of this study was to investigate the potential relationships between cerebrospinal fluid (CSF) measurements of beta-amyloid-1-42 (Abeta(1-42)) and total tau to (11)C-Pittsburgh compound B ((11)C-PiB) and 2-(1-{6-[(2-(18)F-fluoroethyl)(methyl)amino]-2-naphthyl}ethylidene) malononitrile ((18)F-FDDNP) binding as measured using PET. METHODS: A total of 37 subjects were included, consisting of 15 patients with Alzheimer disease (AD), 12 patients with mild cognitive impairment, and 10 healthy controls. All subjects underwent a lumbar puncture and PET using both (11)C-PiB and (18)F-FDDNP. For both PET tracers, parametric images of binding potential were generated. Potential associations of CSF levels of Abeta(1-42) and tau with (11)C-PiB and (18)F-FDDNP binding were assessed using Pearson correlation coefficients and linear regression analyses. RESULTS: For both global (11)C-PiB and (18)F-FDDNP binding, significant correlations with CSF levels of Abeta(1-42) (r = -0.72 and -0.37, respectively) and tau (r = 0.58 and 0.56, respectively) were found across groups (all P < 0.001, except P < 0.05 for correlation between (18)F-FDDNP and Abeta(1-42)). Linear regression analyses showed that, adjusted for regional volume, age, sex, and diagnosis, global (11)C-PiB uptake had an inverse association with Abeta(1-42) CSF levels (standardized beta = -0.50, P < 0.001), whereas there was a positive association between global (18)F-FDDNP binding and tau CSF levels (standardized beta = 0.62, P < 0.01). CONCLUSION: The good agreement between these 2 different types of biomarkers (i.e., CSF and PET) provides converging evidence for their validity. The inverse association between (11)C-PiB and CSF tau Abeta(1-42) confirms that (11)C-PiB measures amyloid load in the brain. The positive association between (18)F-FDDNP and CSF tau suggests that at least part of the specific signal of (18)F-FDDNP in AD patients is due to tangle formation. SN - 0161-5505 UR - https://www.unboundmedicine.com/medline/citation/19690025/Relationship_of_cerebrospinal_fluid_markers_to_11C_PiB_and_18F_FDDNP_binding_ L2 - http://jnm.snmjournals.org/cgi/pmidlookup?view=long&amp;pmid=19690025 DB - PRIME DP - Unbound Medicine ER -