Abstract
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Introduction: Multiple sclerosis (MS) is the most common demyelinating disease in human, affecting more than 2 million people worldwide. Drugs promoting myelin repair represent a promising therapeutic approach and several molecules are currently being evaluated. A reliable imaging method to specifically quantify myelin in vivo is crucially needed to test the efficacy of these drugs. 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 humans, but it is characterized by a suboptimal signal-to-noise ratio. Another promising class of radiopharmaceutical compounds is the family of stilbene derivatives, such as 11C-BMB and 11C-MeDAS, which have been shown to bind to myelin in animal models. Fluorinated analogues 18F-florbetapir and 18F-florbetaben, belonging to these chemical classes, are now commercially available and may offer clinically useful radiotracers for myelin imaging.
Objectives: This study aimed to compare 11C-MeDAS, 18F-florbetapir and 18F-florbetaben with 11C-PiB, with regard to brain kinetic properties and discriminative potential between white (WM) and grey matter (GM) binding.
Methods: Four healthy baboons (27.2 ± 2.3 kg) were included in the study and underwent a PET scan for each radioligand, with a minimum rest period of 2 weeks. Dynamic cerebral PET scans were acquired during 90 minutes under propofol anesthesia after radiotracer injection (244.6 ±.37.8 MBq). The brain kinetic of each radiotracer, expressed as standardized uptake values (SUV), were evaluated in terms of (1) radioligand uptake in the WM, (2) binding ratio of WM over GM (ratioWM/GM) and (3) stability of the ratioWM/GM over the scan duration.
Results: The brain distribution was comparable across the four radiotracers, with a greater uptake in the WM compared to the GM. (1) The WM uptake of 18F-florbetaben (SUV90min = 1.72 ± 0.10) was higher than that of 11C-MeDAS (SUV90min = 1.68 ± 0.20), 18F-florbetapir (SUV90min = 1.47 ± 0.20) and 11C-PiB (SUV90min = 0.46 ± 0.05). (2) RatioWM/GMmeasured at 90 minutes post-injection of 18F-florbetapir (1.28 ± 0.03) and 18F-florbetaben (1.25 ± 0.04), were higher than that of 11C-MeDAS (1.19 ± 0.02) and 11C-PiB (1.17 ± 0.04). (3) The ratioWM/GM reached an equilibrium at 50 minutes post injection for 11C-PiB, but this equilibrium was not reached over the PET exam for the other tested radiotracers.
Conclusions: All the stilbene derivatives showed a higher WM uptake and ratioWM/GM, compared to 11C-PiB, which supports their use as alternative myelin PET tracers. Fluorinated radiotracers showed higher ratioWM/GM compared with carbone-11 radiolabelled ones. Only 11C-PiB reached a stable ratioWM/GM over the PET scan duration.