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Gomez, Luis FAuthor

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November 12, 2025
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Monoamine oxidase binding not expected to significantly affect [18F]flortaucipir PET interpretation

Publicated to: European Journal Of Nuclear Medicine And Molecular Imaging. 49 (11): 3797-3808 - 2022-05-21 49(11), DOI: 10.1007/s00259-022-05822-9

Authors:

Wright, Justin P; Wright, Justin P; Goodman, Jason R; Goodman, Jason R; Lin, Yin-Guo; Lieberman, Brian P; Lieberman, Brian P; Clemens, Jennifer; Gomez, Luis F; Gomez, Luis F; Liang, Qianwa; Hoye, Adam T; Hoye, Adam T; Pontecorvo, Michael J; Pontecorvo, Michael J; Conway, Kelly A; Conway, Kelly A
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Affiliations

Eli Lilly & Co, Avid Radiopharmaceut, Philadelphia, PA 19104 USA - Author

Abstract

Purpose [F-18]-labeled positron emission tomography (PET) radioligands permit in vivo assessment of Alzheimer's disease biomarkers, including aggregated neurofibrillary tau (NFT) with [F-18]flortaucipir. Due to structural similarities of flortaucipir with some monoamine oxidase A (MAO-A) inhibitors, this study aimed to evaluate flortaucipir binding to MAO-A and MAO-B and any potential impact on PET interpretation. Methods [F-18]Flortaucipir autoradiography was performed on frozen human brain tissue slices, and PET imaging was conducted in rats. Dissociation constants were determined by saturation binding, association and dissociation rates were measured by kinetic binding experiments, and IC50 values were determined by competition binding. Results Under stringent wash conditions, specific [F-18]flortaucipir binding was observed on tau NFT-rich Alzheimer's disease tissue and not control tissue. In vivo PET experiments in rats revealed no evidence of [F-18]flortaucipir binding to MAO-A; pre-treatment with MAO inhibitor pargyline did not impact uptake or wash-out of [F-18]flortaucipir. [F-18]Flortaucipir bound with low nanomolar affinity to human MAO-A in a microsomal preparation in vitro but with a fast dissociation rate relative to MAO-A ligand fluoroethyl-harmol, consistent with no observed in vivo binding in rats of [F-18]flortaucipir to MAO-A. Direct binding of flortaucipir to human MAO-B was not detected in a microsomal preparation. A high concentration of flortaucipir (IC50 of 1.3 mu M) was found to block binding of the MAO-B ligand safinamide to MAO-B on microsomes suggesting that, at micromolar concentrations, flortaucipir weakly binds to MAO-B in vitro. Conclusion These data suggest neither MAO-A nor MAO-B binding will contribute significantly to the PET signal in cortical target areas relevant to the interpretation of [F-18]flortaucipir.
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Keywords

Alzheimer's diseaseAlzheimers-diseaseAmyloid-beta plaquesBrainDementiaDiagnosisEmission-tomography tracerFlortaucipirIn-vitroLocalizationMao-bMonoamine oxidasePaired helical filamentsPetTau neurofibrillary tangles

Quality index

Bibliometric impact. Analysis of the contribution and dissemination channel

The work has been published in the journal European Journal Of Nuclear Medicine And Molecular Imaging due to its progression and the good impact it has achieved in recent years, according to the agency WoS (JCR), it has become a reference in its field. In the year of publication of the work, 2022, it was in position 7/135, thus managing to position itself as a Q1 (Primer Cuartil), in the category Radiology, Nuclear Medicine & Medical Imaging. Notably, the journal is positioned above the 90th percentile.

Independientemente del impacto esperado determinado por el canal de difusión, es importante destacar el impacto real observado de la propia aportación.

Según las diferentes agencias de indexación, el número de citas acumuladas por esta publicación hasta la fecha 2026-01-22:

  • WoS: 10
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Impact and social visibility

From the perspective of influence or social adoption, and based on metrics associated with mentions and interactions provided by agencies specializing in calculating the so-called "Alternative or Social Metrics," we can highlight as of 2026-01-22:

  • The use, from an academic perspective evidenced by the Altmetric agency indicator referring to aggregations made by the personal bibliographic manager Mendeley, gives us a total of: 10.
  • The use of this contribution in bookmarks, code forks, additions to favorite lists for recurrent reading, as well as general views, indicates that someone is using the publication as a basis for their current work. This may be a notable indicator of future more formal and academic citations. This claim is supported by the result of the "Capture" indicator, which yields a total of: 10 (PlumX).

With a more dissemination-oriented intent and targeting more general audiences, we can observe other more global scores such as:

  • The Total Score from Altmetric: 10.
  • The number of mentions on the social network X (formerly Twitter): 1 (Altmetric).
  • The number of mentions in news outlets: 1 (Altmetric).
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Leadership analysis of institutional authors

This work has been carried out with international collaboration, specifically with researchers from: United States of America.

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Awards linked to the item

This research is funded by Eli Lilly/Avid Radiopharmaceuticals.
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