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

Complete text of publication follows: 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 (ratio WM/GM) and (3) stability of the ratio WM/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 (SUV_90min = 1.72 ± 0.10) was higher than that of ¹¹C-MeDAS (SUV_90min = 1.68 ± 0.20), ¹⁸F-florbetapir (SUV_90min = 1.47 ± 0.20) and ¹¹C-PiB (SUV_90min = 0.46 ± 0.05). (2) Ratio WM/GM measured 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 ratio WM/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 ratio WM/GM, compared to ¹¹C-PiB, which supports their use as alternative myelin PET tracers. Fluorinated radiotracers showed higher ratio WM/GM compared with carbon-11 radiolabelled ones. Only ¹¹C-PiB reached a stable ratio WM/GM over the PET scan duration