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Correlation of amyloid PET ligand florbetapir F 18 binding with Aβ aggregation and neuritic plaque deposition in postmortem brain tissue.
Alzheimer Dis Assoc Disord. 2012 Jan-Mar; 26(1):8-16.AD

Abstract

BACKGROUND

Florbetapir F 18 (F-AV-45) is a positron emission tomography imaging ligand for the detection of amyloid aggregation associated with Alzheimer disease. Earlier data showed that florbetapir F 18 binds with high affinity to β-amyloid (Aβ) plaques in human brain homogenates (Kd=3.7 nM) and has favorable imaging pharmacokinetic properties, including rapid brain penetration and washout. This study used human autopsy brain tissue to evaluate the correlation between in vitro florbetapir F 18 binding and Aβ density measured by established neuropathologic methods.

METHODS

The localization and density of florbetapir F 18 binding in frozen and formalin-fixed paraffin-embedded sections of postmortem brain tissue from 40 patients with a varying degree of neurodegenerative pathology was assessed by standard florbetapir F 18 autoradiography and correlated with the localization and density of Aβ identified by silver staining, thioflavin S staining, and immunohistochemistry.

RESULTS

There were strong quantitative correlations between florbetapir F 18 tissue binding and both Aβ plaques identified by light microscopy (Silver staining and thioflavin S fluorescence) and by immunohistochemical measurements of Aβ using 3 antibodies recognizing different epitopes of the Aβ peptide. Florbetapir F 18 did not bind to neurofibrillary tangles.

CONCLUSIONS

Florbetapir F 18 selectively binds Aβ in human brain tissue. The binding intensity was quantitatively correlated with the density of Aβ plaques identified by standard neuropathologic techniques and correlated with the density of Aβ measured by immunohistochemistry. As Aβ plaques are a defining neuropathologic feature for Alzheimer disease, these results support the use of florbetapir F 18 as an amyloid positron emission tomography ligand to identify the presence of Alzheimer disease pathology in patients with signs and symptoms of progressive late-life cognitive impairment.

Authors+Show Affiliations

Avid Radiopharmaceutical Inc., 3711 Market Street, 7th Floor, Philadelphia, PA 19104, USA.No affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info available

Pub Type(s)

Journal Article
Research Support, N.I.H., Extramural
Research Support, Non-U.S. Gov't

Language

eng

PubMed ID

22354138

Citation

Choi, Seok Rye, et al. "Correlation of Amyloid PET Ligand Florbetapir F 18 Binding With Aβ Aggregation and Neuritic Plaque Deposition in Postmortem Brain Tissue." Alzheimer Disease and Associated Disorders, vol. 26, no. 1, 2012, pp. 8-16.
Choi SR, Schneider JA, Bennett DA, et al. Correlation of amyloid PET ligand florbetapir F 18 binding with Aβ aggregation and neuritic plaque deposition in postmortem brain tissue. Alzheimer Dis Assoc Disord. 2012;26(1):8-16.
Choi, S. R., Schneider, J. A., Bennett, D. A., Beach, T. G., Bedell, B. J., Zehntner, S. P., Krautkramer, M. J., Kung, H. F., Skovronsky, D. M., Hefti, F., & Clark, C. M. (2012). Correlation of amyloid PET ligand florbetapir F 18 binding with Aβ aggregation and neuritic plaque deposition in postmortem brain tissue. Alzheimer Disease and Associated Disorders, 26(1), 8-16. https://doi.org/10.1097/WAD.0b013e31821300bc
Choi SR, et al. Correlation of Amyloid PET Ligand Florbetapir F 18 Binding With Aβ Aggregation and Neuritic Plaque Deposition in Postmortem Brain Tissue. Alzheimer Dis Assoc Disord. 2012 Jan-Mar;26(1):8-16. PubMed PMID: 22354138.
* Article titles in AMA citation format should be in sentence-case
TY - JOUR T1 - Correlation of amyloid PET ligand florbetapir F 18 binding with Aβ aggregation and neuritic plaque deposition in postmortem brain tissue. AU - Choi,Seok Rye, AU - Schneider,Julie A, AU - Bennett,David A, AU - Beach,Thomas G, AU - Bedell,Barry J, AU - Zehntner,Simone P, AU - Krautkramer,Michael J, AU - Kung,Hank F, AU - Skovronsky,Daniel M, AU - Hefti,Franz, AU - Clark,Christopher M, PY - 2012/2/23/entrez PY - 2012/2/23/pubmed PY - 2012/6/21/medline SP - 8 EP - 16 JF - Alzheimer disease and associated disorders JO - Alzheimer Dis Assoc Disord VL - 26 IS - 1 N2 - BACKGROUND: Florbetapir F 18 (F-AV-45) is a positron emission tomography imaging ligand for the detection of amyloid aggregation associated with Alzheimer disease. Earlier data showed that florbetapir F 18 binds with high affinity to β-amyloid (Aβ) plaques in human brain homogenates (Kd=3.7 nM) and has favorable imaging pharmacokinetic properties, including rapid brain penetration and washout. This study used human autopsy brain tissue to evaluate the correlation between in vitro florbetapir F 18 binding and Aβ density measured by established neuropathologic methods. METHODS: The localization and density of florbetapir F 18 binding in frozen and formalin-fixed paraffin-embedded sections of postmortem brain tissue from 40 patients with a varying degree of neurodegenerative pathology was assessed by standard florbetapir F 18 autoradiography and correlated with the localization and density of Aβ identified by silver staining, thioflavin S staining, and immunohistochemistry. RESULTS: There were strong quantitative correlations between florbetapir F 18 tissue binding and both Aβ plaques identified by light microscopy (Silver staining and thioflavin S fluorescence) and by immunohistochemical measurements of Aβ using 3 antibodies recognizing different epitopes of the Aβ peptide. Florbetapir F 18 did not bind to neurofibrillary tangles. CONCLUSIONS: Florbetapir F 18 selectively binds Aβ in human brain tissue. The binding intensity was quantitatively correlated with the density of Aβ plaques identified by standard neuropathologic techniques and correlated with the density of Aβ measured by immunohistochemistry. As Aβ plaques are a defining neuropathologic feature for Alzheimer disease, these results support the use of florbetapir F 18 as an amyloid positron emission tomography ligand to identify the presence of Alzheimer disease pathology in patients with signs and symptoms of progressive late-life cognitive impairment. SN - 1546-4156 UR - https://www.unboundmedicine.com/medline/citation/22354138/Correlation_of_amyloid_PET_ligand_florbetapir_F_18_binding_with_Aβ_aggregation_and_neuritic_plaque_deposition_in_postmortem_brain_tissue_ L2 - http://dx.doi.org/10.1097/WAD.0b013e31821300bc DB - PRIME DP - Unbound Medicine ER -