Dual-phase [18F]florbetapir in frontotemporal dementia

Abstract

Purpose: The PET tracer [18F]florbetapir is a specific fibrillar amyloid-beta (Aβ) biomarker. During the late scan phase (> 40 min), it provides pathological information about Aβ status. Early scan phase (0-10 min) can provide FDG-'like' information. The current investigation tested the feasibility of using florbetapir as a dual-phase biomarker in behavioural variant frontotemporal dementia (bvFTD).

Methods: Eight bvFTD patients underwent [18F]florbetapir and [18]FDG-PET scans. Additionally, ten healthy controls and ten AD patients underwent florbetapir-PET only. PET data were acquired dynamically for 60-min post-injection. The bvFTD PET data were used to define an optimal time window, representing blood flow-related pseudo-metabolism ('pseudo-FDG'), of florbetapir data that maximally correlated with the corresponding real FDG SUVR (40-60 min) in a composite neocortical FTD region.

Results: A 2 to 5-min time window post-injection of the florbetapir-PET data provided the largest correlation (Pearson's r = 0.79, p = 0.02) to the FDG data. The pseudo-FDG images demonstrated strong internal consistency with actual FDG data and were also visually consistent with the bvFTD patients' hypometabolic profiles. The ability to identify bvFTD from blind visual rating of pseudo-FDG images was consistent with previous reports using FDG data (sensitivity = 75%, specificity = 85%).

Conclusions: This investigation demonstrates that early phase florbetapir uptake shows a reduction of frontal lobe perfusion in bvFTD, similar to metabolic findings with FDG. Thus, dynamic florbetapir scans can serve as a dual-phase biomarker in dementia patients to distinguish FTD from AD and cognitively normal elderly, removing the need for a separate FDG-PET scan in challenging dementia cases.

Keywords: Dual-biomarker; FDG; Florbetapir; PET; bvFTD.

Fig. 1

Bland–Altman plot measuring the agreement between the pseudo-FDG and FDG SUVRs in the meta-FTD region from the bvFTD patients. A zero difference would indicate both methods provide the same result; all values lie within 95% confidence limits

Fig. 2

Surface renderings of BPM voxel-wise correlations for bvFTD FDG vs pseudo-FDG SUVR images; k = 50 voxels, p = 0.01 uncorrected, 6-mm smoothing. The colour bar represents r values. Positive neocortical correlations are present within the same frontal and anterior temporal cortical regions contained in the FTD meta-region. Additional correlations are also observed in regions that include bilateral inferior temporal gyrus, left middle temporal, left superior temporal, and left angular gyri

Fig. 3

All imaging data from the bvFTD patients is displayed. Each row represents data from a single patient; each column represents coregistered images in axial and coronal slices for T1 MRI, florbetapir, FDG, and pseudo-FDG. The Colour bars represent SUVR values. A clear visual correspondence is seen in the hypometabolic patterns from the FDG images and the pseudo-FDG images

Fig. 4

Surface renderings of SPM t test for CN > bvFTD (pseudo-FDG; florbetapir 2–5 min SUVR); k = 50 voxels, p = 0.001 uncorrected, 6-mm smoothing. The colour bar represents t values. For the pseudo-FDG images a clear pattern of frontal and anterior temporal hypometabolism is visually evident

Fig. 5

Surface renderings of SPM t test for AD > bvFTD (pseudo-FDG; florbetapir 2–5 min SUVR); k = 50 voxels, p = 0.001 uncorrected, 6-mm smoothing. The colour bar represents t values. A clear medial frontal pattern of hypometabolism is seen between the patient groups, with differences also in anterior temporal and occipital cortex