(+)-[18F]Flubatine as a novel α4β2 nicotinic acetylcholine receptor PET ligand—results of the first-in-human brain imaging application in patients with β-amyloid PET-confirmed Alzheimer’s disease and healthy controls

Purposes We present the first in-human brain PET imaging data of the new α4β2 nicotinic acetylcholine receptor (nAChR)–targeting radioligand (+)-[ 18 F]Flubatine. Aims were to develop a kinetic modeling-based approach to quantify (+)-[ 18 F]Flubatine and compare the data of healthy controls (HCs) and patients with Alzheimer’s disease (AD); to investigate the partial volume effect (PVE) on regional (+)-[ 18 F]Flubatine binding; and whether (+)-[ 18 F]Flubatine binding and cognitive test data respective β-amyloid radiotracer accumulation were correlated. Methods We examined 11 HCs and 9 mild AD patients. All subjects underwent neuropsychological testing and [ 11 C]PiB PET/MRI examination. (+)-[ 18 F]Flubatine PET data were evaluated using full kinetic modeling and regional as well as voxel-based analyses. Results With 270-min p.i., the unchanged parent compound amounted to 97 ± 2%. Adequate fits of the time-activity curves were obtained with the 1 tissue compartment model (1TCM). (+)-[ 18 F]Flubatine distribution volume (binding) was significantly reduced in bilateral mesial temporal cortex in AD patients compared with HCs (right 10.6 ± 1.1 vs 11.6 ± 1.4, p = 0.049; left 11.0 ± 1.1 vs 12.2 ± 1.8, p = 0.046; one-sided t tests each). PVE correction increased not only (+)-[ 18 F]Flubatine binding of approximately 15% but also standard deviation of 0.4–70%. Cognitive test data and (+)-[ 18 F]Flubatine binding were significantly correlated in the left anterior cingulate, right posterior cingulate, and right parietal cortex ( r > 0.5, p