[18F]Florbetapir PET/MR imaging to assess demyelination in multiple sclerosis

Abstract

Purpose We evaluated myelin changes throughout the central nervous system in Multiple Sclerosis (MS) patients by using hybrid [ 18 F]florbetapir PET-MR imaging. Methods We included 18 relapsing-remitting MS patients and 12 healthy controls. Each subject performed a hybrid [ 18 F]florbetapir PET-MR and both a clinical and cognitive assessment. [ 18 F]florbetapir binding was measured as distribution volume ratio (DVR), through the Logan graphical reference method and the supervised cluster analysis to extract a reference region, and standard uptake value (SUV) in the 70-90 min interval after injection. The two quantification approaches were compared. We also evaluated changes in the measures derived from diffusion tensor imaging and arterial spin labeling. Results [ 18 F]florbetapir DVRs decreased from normal-appearing white matter to the centre of T2 lesion (P < 0.001), correlated with fractional anisotropy and with mean, axial and radial diffusivity within T2 lesions (coeff. = −0.15, P < 0.001, coeff. = −0.12, P < 0.001 and coeff. = −0.16, P < 0.001, respectively). Cerebral blood flow was reduced in white matter damaged areas compared to white matter in healthy controls (−10.9%, P = 0.005). SUV 70-90 and DVR are equally able to discriminate between intact and damaged myelin (area under the curve 0.76 and 0.66, respectively; P = 0.26). Conclusion Our findings demonstrate that [ 18 F]florbetapir PET imaging can measure in-vivo myelin damage in patients with MS. Demyelination in MS is not restricted to lesions detected through conventional MRI but also involves the normal appearing white matter. Although longitudinal studies are needed, [ 18 F]florbetapir PET imaging may have a role in clinical settings in the management of MS patients.

18F-florbetapir PET/MRI for quantitatively monitoring myelin loss and recovery in patients with multiple sclerosis: A longitudinal study

“…Second, EDSS and myelin changes were correlated in the longitudinal 18 F-florbetapir PET study, suggesting that myelin recovery might contribute to the decrease in EDSS score. Previous [ 12 , 22 ] and our present studies showed that EDSS was not related to 11 C-PiB or 18 F-florbetapir DVR in T2 lesions at baseline. Therefore, longitudinal amyloid PET reflecting the balance between the loss and recovery of myelin in patients with MS could better assess the development of clinical disease status of MS and disease-modifying treatments.…”

“…[12] and Carotenuto A, et al. [22] have reported a decreased binding of amyloid tracer in the area 2 to 8 mm outside the edge of the T2 lesion, suggesting that the range of demyelinating lesions reflected by amyloid PET might be larger than that defined by T2WI.…”

“…To avoid blood sampling in our patient cohort, we chose to quantify our dynamic PET scans using a reference region approach. According to the supervised clustering method already validated for the extraction of the reference region time activity curve of 11 C-PiB [ 12 , 13 ] or 18 F-florbetapir [22] , normal GM was selected as a reference region. The Logan graphical reference method [27] was then applied at the voxel level on PET scans to produce a parametric map of 18 F-florbetapir binding measured as the distribution volume ratio (DVR, defined as the ratio of the total distribution volume between the target and the reference region).…”

“…Therefore, second-generation 18 F (approximately 110 min)-labeled tracers with higher WM binding rates need to be developed. A recent study has shown that 18 F-labeled amyloid tracers such as 18 F-florbetapir and 18 F-florbetaben have higher binding of WM than 11 C-PiB [19] , and a few research teams, including our team, have carried out myelin PET imaging using 18 F-florbetapir [20] , [21] , [22] and 18 F-florbetaben [ 23 , 24 ] for clinical practice. Although a pioneering longitudinal study using 11 C-PiB from Bodini B, et al.…”

Metals in Imaging of Alzheimer’s Disease

“…But using these drugs requires an expensive laborious synthesis with confirmation of radio purity at each stage. The short half-lives of the currently used radionuclides 11 C (20.4 min) and 18 F (109.8 min) may also limit the widespread use of these imaging agents [11,12].…”