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Repurposing stilbene derivatives as myelin radiotracers for PET imaging: a study comparing 11C-MeDAS, 18F-florbetapir and 18F-florbetaben with the benzothiazole 11C-PiB
Author(s): ,
M. Tonietto
Affiliations:
Sorbonne Universités, UPMC Paris 06, Brain and Spine Institute, ICM, Hôpital de la Pitié Salpêtrière, Inserm UMR S 1127, CNRS UMR 7225
,
S. Auvity
Affiliations:
Inserm, U1144, Paris; IMIV, CEA, Inserm, CNRS, Univ. Paris-Sud, Université Paris Saclay, CEA-SHFJ, Orsay
,
F. Caillé
Affiliations:
IMIV, CEA, Inserm, CNRS, Univ. Paris-Sud, Université Paris Saclay, CEA-SHFJ, Orsay
,
B. Bodini
Affiliations:
Sorbonne Universités, UPMC Paris 06, Brain and Spine Institute, ICM, Hôpital de la Pitié Salpêtrière, Inserm UMR S 1127, CNRS UMR 7225; Neurology Department, APHP, St Antoine Hospital, Paris, France
,
M. Bottlaender
Affiliations:
IMIV, CEA, Inserm, CNRS, Univ. Paris-Sud, Université Paris Saclay, CEA-SHFJ, Orsay
,
N. Tournier
Affiliations:
IMIV, CEA, Inserm, CNRS, Univ. Paris-Sud, Université Paris Saclay, CEA-SHFJ, Orsay
,
B. Kuhnast
Affiliations:
IMIV, CEA, Inserm, CNRS, Univ. Paris-Sud, Université Paris Saclay, CEA-SHFJ, Orsay
B. Stankoff
Affiliations:
Sorbonne Universités, UPMC Paris 06, Brain and Spine Institute, ICM, Hôpital de la Pitié Salpêtrière, Inserm UMR S 1127, CNRS UMR 7225; Neurology Department, APHP, St Antoine Hospital, Paris, France
ECTRIMS Online Library. Tonietto M. Oct 12, 2018; 228967
Matteo Tonietto
Matteo Tonietto
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Abstract: P1127

Type: Poster Sessions

Abstract Category: Pathology and pathogenesis of MS - MRI and PET

Introduction: Drugs promoting myelin repair represent a promising therapeutic approach in MS and several candidate molecules are currently being evaluated1, fostering the need of a quantitative method to specifically measure myelin in vivo. Positron Emission Tomography (PET) using the benzothiazole derivative 11C-PiB, repurposed as a myelin biomarker, has been successfully used to quantify myelin content changes in humans2, even with its low signal-to-noise ratio. Another promising class of radiopharmaceuticals is the family of stilbene derivatives, such as 11C-MeDAS, which has been shown to bind to myelin in preclinical models3. Fluorinated analogues 18F-florbetapir and 18F-florbetaben are now commercially available and have the potential to be clinically useful radiotracers for myelin imaging.
Aims: The aim of this study was to compare 18F-florbetaben, 18F-florbetapir and 11C-MeDAS with 11C-PiB, with regard to brain uptake and binding to white matter (WM).
Methods: Four healthy baboons (weight: 27.2±2.3 kg) underwent a 90 min dynamic PET scan for each radioligand (injected dose: 244.6±37.8 MBq). A T1-weighted (T1-w) image was also acquired with a 1.5T MRI scanner for each subject. All PET images were rigidly aligned to the subject T1-w, which was segmented in cerebral spinal fluid, WM and grey matter (GM). The tracer uptake in the WM was evaluated using standardized uptake value ratio between 75 at 90 min (SUVR), and the distribution volume ratio (DVR) calculated with Logan graphical reference method. Cerebellar GM was used as reference region for both methods. Statistical analysis was performed using mixed effect models.
Results: In WM, 18F-florbetapir had the highest SUVR (1.38±0.03), followed by 18F-florbetaben (1.32±0.07, p=0.04). Both 11C-MeDAS and 11C-PiB had a statically lower SUVR than 18F-florbetaben (1.27±0.04, p=0.04; 1.25±0.07, p=0.04 respectively). No difference in DVR was detected between 18F-florbetaben and 18F-florbetapir (1.26±0.06 and 1.27±0.03 respectively, p=0.38), but both tracers were statistically higher than 11C-MeDAS (1.16±0.03, p< 0.001) and 11C-PiB (1.14 ± 0.02, p< 0.001).
Conclusion: Given their higher SUVR, DVR and longer half-life compared to 11C-PiB, our study indicates that 18F-florbetapir and 18F-florbetaben are promising tracers for clinical application in MS and other demyelinating diseases.
References:
1Plemel, Nat. Rev. Drug Discov. (2017)
2Bodini, Ann. Neurol. (2016)
3Wu, Bioorg. Med. Chem. (2010)
Disclosure: MT: nothing to disclose
SA: nothing to disclose
FC: nothing to disclose
B. Bodini receives research support from ARSEP. She has received funding for traveling and/or speaker's honoraria from Novartis, Genzyme, Roche and Merck Serono.
MB: nothing to disclose
NT: nothing to disclose
BK: nothing to disclose
Pr B. Stankoff received honoraria from Biogen, Teva, Novartis, Genzyme, Roche and research support from Genzyme, Merck-Serono and Roche.

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