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

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 C-11-PiB has been successfully used to quantify myelin content changes in humans. Stilbene derivatives, such as C-11-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-18-florbetaben, F-18-florbetapir, F-18-flutemetamol, C-11-MeDAS, and C-11-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 F-18-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, F-18-florbetapir had the highest SUVR75-90 (1.38 +/- 0.03), followed by F-18-flutemetamol (1.34 +/- 0.02), F-18-florbetaben (1.32 +/- 0.07), C-11-MeDAS (1.27 +/- 0.04), and C-11-PiB (1.25 +/- 0.07). With regard to BP, F-18-florbetaben had the highest value (0.32 +/- 0.06) compared with F-18-flutemetamol (0.20 +/- 0.03), C-11-MeDAS (0.17 +/- 0.03), and C-11-PiB (0.16 +/- 0.03). No difference in DVR was detected between F-18-florbetaben (1.26 +/- 0.06) and F-18-florbetapir (1.27 +/- 0.03), but both were significantly higher in DVR than F-18-flutemetamol (1.17 +/- 0.02), C-11-MeDAS (1.16 +/- 0.03), and C-11-PiB (1.14 +/- 0.02). Conclusions Given their higher binding and longer half-life, our study indicates that F-18-florbetapir and F-18-florbetaben are promising tracers for myelin imaging which are readily available for clinical application in demyelinating diseases.