Optimal parametric imaging methods for dual‐time‐window [18F]flutemetamol and [18F]florbetaben PET studies

Abstract

AbstractBackgroundAccurate quantitative measures of amyloid beta (Aβ) plaques are needed to identify individuals with subthreshold Aβ levels or for measuring small changes over time. To this end, dynamic or dual‐time‐window scanning protocols are required. Optimal pharmacokinetic models for quantifying Aβ burden using both [18F]flutemetamol and [18F]florbetaben dual‐time‐window scans have previously been identified at a region of interest (ROI) level. This study aimed to determine optimal parametric methods for analyses of [18F]flutemetamol and [18F]florbetaben dual‐time‐window scans.MethodForty‐six participants were scanned on a PET/MR scanner using a dual‐time‐window protocol and either [18F]flutemetamol or [18F]florbetaben. The following parametric approaches were used to derive DVR estimates: reference Logan (RLogan), receptor parametric mapping (RPM), two‐step simplified reference tissue model (SRTM2) and multilinear reference tissue models (MRTM0, MRTM1, MRTM2), all with cerebellar grey matter as reference tissue. In addition, a standardized uptake value ratio (SUVR) was calculated for the 90‐110 min post injection interval. All parametric images were assessed visually for possible image artefacts and regional cortical outcome measures were compared with DVR derived using regional RLogan, based on AUC values for differentiating between Aβ‐positive and Aβ‐negative scans, Bland‐Altman plots and linear regression analyses.ResultVisually, RPM and SRTM2 performed best across tracers and, in addition to SUVR, provided the highest AUC values for differentiating between Aβ‐positive and Aβ‐negative scans ([18F]flutemetamol: range AUC=0.96‐0.97, [18F]florbetaben: range AUC=0.83‐0.85). Outcome parameters of most methods were highly correlated with those of the reference method (R2≥0.87), with lowest correlations observed for MRTM2 (R2=0.71‐0.80). Furthermore, bias was low (≤5%) and independent of underlying amyloid burden for MRTM0 and MRTM1. On the other hand, bias in SUVR was high for [18F]flutemetamol (mean bias>10%), but low for [18F]florbetaben (mean bias=1%) and strongly proportional with underlying Aβ burden for both tracers.ConclusionThe best overall compromise was provided by MRTM0, followed closely by SRTM2. SRTM2 is the preferred method for parametric imaging because, in addition to its good performance, it has the advantage of providing a measure of relative perfusion (R1), which is useful for measuring disease progression. “This work has received support from the EU‐EFPIA Innovative Medicines Initiatives 2 Joint Undertaking (grant No 115952).”