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

Abstract

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 ¹¹C-PiB has been successfully used to quantify myelin content changes in humans. Stilbene derivatives, such as ¹¹C-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 ¹⁸F-florbetaben, ¹⁸F-florbetapir, ¹⁸F-flutemetamol, ¹¹C-MeDAS, and ¹¹C-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 ¹⁸F-florbetapir, to obtain a radiometabolite-corrected input function. Standardized uptake value ratio between 75 at 90 min (SUVR_75-90), 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, ¹⁸F-florbetapir had the highest SUVR_75-90 (1.38 ± 0.03), followed by ¹⁸F-flutemetamol (1.34 ± 0.02), ¹⁸F-florbetaben (1.32 ± 0.07), ¹¹C-MeDAS (1.27 ± 0.04), and ¹¹C-PiB (1.25 ± 0.07). With regard to BP, ¹⁸F-florbetaben had the highest value (0.32 ± 0.06) compared with ¹⁸F-flutemetamol (0.20 ± 0.03), ¹¹C-MeDAS (0.17 ± 0.03), and ¹¹C-PiB (0.16 ± 0.03). No difference in DVR was detected between ¹⁸F-florbetaben (1.26 ± 0.06) and ¹⁸F-florbetapir (1.27 ± 0.03), but both were significantly higher in DVR than ¹⁸F-flutemetamol (1.17 ± 0.02), ¹¹C-MeDAS (1.16 ± 0.03), and ¹¹C-PiB (1.14 ± 0.02).

Conclusions: Given their higher binding and longer half-life, our study indicates that ¹⁸F-florbetapir and ¹⁸F-florbetaben are promising tracers for myelin imaging which are readily available for clinical application in demyelinating diseases.

Keywords: Benzothiazole; Multiple sclerosis; Myelin; PET imaging; Stilbene.