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

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

Publication date: Nov 04, 2019

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 C-PiB has been successfully used to quantify myelin content changes in humans. Stilbene derivatives, such as C-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 F-florbetaben, F-florbetapir, F-flutemetamol, C-MeDAS, and C-PiB with regard to brain kinetics and binding in white matter (WM).

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 F-florbetapir, to obtain a radiometabolite-corrected input function. Standardized uptake value ratio between 75 at 90 min (SUVR), 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.

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

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

Auvity, S., Tonietto, M., Caill’e, F., Bodini, B., Bottlaender, M., Tournier, N., Kuhnast, B., and Stankoff, B. Repurposing radiotracers for myelin imaging: a study comparing 18F-florbetaben, 18F-florbetapir, 18F-flutemetamol,11C-MeDAS, and 11C-PiB. 19446. 2019 Eur J Nucl Med Mol Imaging.

Concepts Keywords
Blood Radiotracers myelin imaging
BP Therapeutic multiple sclerosis
Brain Alzheimer’s disease
Cerebellar Radiocontrast agents
Demyelinating Diseases Organofluorides
Derivative Chemical compounds
DVR Chemical substances
Gray Matter Branches of biology
Kinetics Florbetaben
Multiple Sclerosis Positron emission tomography
Myelin Florbetapir
PET Flutemetamol
PET Scan Myelin
Radioligand Demyelinating disease
Radiopharmaceutical
Radiotracer
Vivo
White Matter

Semantics

Type Source Name
disease MESH multiple sclerosis
disease DOID multiple sclerosis
drug DRUGBANK BENZOTHIAZOLE
gene UNIPROT CD69
gene UNIPROT DNMT1
disease MESH demyelinating diseases

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