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Repurposing radiotracers for myelin imaging: a study comparing 18F-florbetaben, 18F-florbetapir, 18F-flutemetamol,11C-MeDAS, and 11C-PiB

  • Sylvain Auvity
  • Matteo Tonietto
  • Fabien Caillé
  • Benedetta Bodini
  • Michel Bottlaender
  • Nicolas Tournier
  • Bertrand Kuhnast
  • Bruno StankoffEmail author
Original Article
  • 78 Downloads
Part of the following topical collections:
  1. Neurology

Abstract

Purpose

Drugs promoting myelin repair represent a promising therapeutic approach in multiple sclerosis and several candidate molecules are currently being evaluated, fostering the need of a quantitative method to specifically measure myelin content in vivo. PET using the benzothiazole derivative 11C-PiB has been successfully used to quantify myelin content changes in humans. Stilbene derivatives, such as 11C-MeDAS, have also been shown to bind to myelin in animals and are considered a promising radiopharmaceutical class for myelin imaging. Fluorinated compounds from both classes are now commercially available and thus should constitute clinically useful myelin radiotracers. The aim of this study is to provide a head-to-head comparison of 18F-florbetaben, 18F-florbetapir, 18F-flutemetamol, 11C-MeDAS, and 11C-PiB with regard to brain kinetics and binding in white matter (WM).

Methods

Four baboons underwent a 90-min dynamic PET scan for each radioligand. Arterial blood samples were collected during the exam for each radiotracer, except for 18F-florbetapir, to obtain a radiometabolite-corrected input function. Standardized uptake value ratio between 75 at 90 min (SUVR75–90), binding potential (BP) estimated with Logan method with input function, and distribution volume ratio (DVR) estimated with Logan reference method (using cerebellar gray matter as reference region) were calculated in WM and compared between tracers using mixed effect models.

Results

In WM, 18F-florbetapir had the highest SUVR75–90 (1.38 ± 0.03), followed by 18F-flutemetamol (1.34 ± 0.02), 18F-florbetaben (1.32 ± 0.07), 11C-MeDAS (1.27 ± 0.04), and 11C-PiB (1.25 ± 0.07). With regard to BP, 18F-florbetaben had the highest value (0.32 ± 0.06) compared with 18F-flutemetamol (0.20 ± 0.03), 11C-MeDAS (0.17 ± 0.03), and 11C-PiB (0.16 ± 0.03). No difference in DVR was detected between 18F-florbetaben (1.26 ± 0.06) and 18F-florbetapir (1.27 ± 0.03), but both were significantly higher in DVR than 18F-flutemetamol (1.17 ± 0.02), 11C-MeDAS (1.16 ± 0.03), and 11C-PiB (1.14 ± 0.02).

Conclusions

Given their higher binding and longer half-life, our study indicates that 18F-florbetapir and 18F-florbetaben are promising tracers for myelin imaging which are readily available for clinical application in demyelinating diseases.

Keywords

Myelin PET imaging Multiple sclerosis Stilbene Benzothiazole 

Notes

Acknowledgments

We thank the scientific committee of the INSIGHT study (Dubois et al., Lancet Neurol. 2018), which was promoted by INSERM, for having kindly provided 18F-florbetapir PET images of test-retest human healthy subjects to verify the reproducibility of 18F-florbetapir in white matter (data not shown). A special thanks to Professor Bruno Dubois, principal investigator of the INSIGHT study, and Christiane Metzinger, who managed the data transfer.

Funding information

This work was performed on a platform of France Life Imaging network partly funded by grant ANR-11-INBS-0006. The study was also funded by a grant from Progressive MS Alliance (collaborative planning award to BS) and CEA. Additional support was received by Fondation ARSEP (to BB) and FRM (Fondation pour la Recherche Médicale, to MT).

Compliance with ethical standards

Conflict of interest

Four doses of 18F-flutemetamol were freely provided by GE Healthcare. No other potential conflicts of interest relevant to this article exist.

Ethical approval

All applicable international, national, and/or institutional guidelines for the care and use of animals were followed.

Supplementary material

259_2019_4516_MOESM1_ESM.docx (1.3 mb)
ESM 1 (DOCX 1348 kb)

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Copyright information

© Springer-Verlag GmbH Germany, part of Springer Nature 2019

Authors and Affiliations

  • Sylvain Auvity
    • 1
  • Matteo Tonietto
    • 2
  • Fabien Caillé
    • 1
  • Benedetta Bodini
    • 2
  • Michel Bottlaender
    • 1
  • Nicolas Tournier
    • 1
  • Bertrand Kuhnast
    • 1
  • Bruno Stankoff
    • 2
    Email author
  1. 1.UMR 1023 IMIV, Service Hospitalier Frédéric Joliot, CEA, Inserm Université Paris Sud, CNRS, Université Paris-SaclayOrsayFrance
  2. 2.Sorbonne Universités, Institut du Cerveau et de la Moelle épinière, ICM, Hôpital de la Pitié Salpêtrière, Inserm UMR S 1127, CNRS UMR 7225ParisFrance

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