Biomarkers

PET imaging plays a critical role in the diagnosis and follow-up of Alzheimer's disease (AD). However, current methods face significant limitations for two key measures: (1) Non-displaceable binding potential (BP_ND) of amyloid-beta (Aβ), which measures Aβ plaque accumulation but requires prolonged >100 min study times; (2) Cerebral blood flow (CBF), an indicator of neurodegeneration which typically requires an additional, separate study. To address these challenges, we developed a novel processing workflow which calculates absolute CBF from standard dynamic Aβ PET scans using our lab's flow-modified 2-tissue compartment model (F2TCM, EJNMMI Res.11:2), and estimates BP_ND from a 20-min dynamic scan post-injection through multiple-fold cross-linear calibration.

Data from 10 patients enrolled in the ongoing BioMind clinical trial data at our institution were used. Each dataset included a 45 min dynamic scan after injection of 300 MBq of 18F-florbetaban and a 10 min scan at 110 min post-injection, acquired with a GE Healthcare OMNI Legend PET/CT scanner. Images were reconstructed using the Q. Clear protocol for higher resolution arterial input function measurements, and the smoother VPHD protocol to improve signal-to-noise for CBF estimation. CBF was calculated using the F2TCM, BP_ND using Logan graphical analysis relative to the cerebellum, and centiloid scores and SUVr were obtained with MIMneuro (MIM Software Inc.).

Figure 1 shows the similarities/differences of CBF maps derived from 3-, 20- and 45-min dynamic scans for three patients with 18F-florbetaben centiloids (SUVr) of 11.1 (1.03), 68.1 (1.38), and 164.4 (1.98), respectively. Voxel-wise comparisons of CBF of all 10 patients showed mean MSE of 18±11 and 156±110 mL/min/100g for 20 and 3 min relative to 45 min, respectively. Figure 2 shows BP_ND maps for a 45 min scan, followed by uncalibrated and calibrated 20 min scans. Calibration slopes, intercepts, uncalibrated and calibrated MSEs were 0.95±0.03, 0.08±0.01, 0.012±0.0044 and 0.0070±0.0013, respectively, based on five-fold cross calibration.

This study highlights the potential of a streamlined 20-minute Aβ PET imaging protocol to measure BP_ND as a surrogate for the centiloid score, while also providing complementary CBF measurements to enhance diagnostic and prognostic utility.