18F-FIBT may expand PET for β-amyloid imaging in neurodegenerative diseases

Grimmer, Timo; Shi, Kuangyu; Diehl-Schmid, Janine; Natale, Bianca; Drzezga, Alexander; Förster, Stefan; Förstl, Hans; Schwaiger, Markus; Yakushev, Igor; Wester, Hans-Jürgen; Kurz, Alexander; Yousefi, Behrooz Hooshyar (2020). 18F-FIBT may expand PET for β-amyloid imaging in neurodegenerative diseases. Molecular psychiatry, 25(10), pp. 2608-2619. Nature Publishing Group 10.1038/s41380-018-0203-5

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18F-FIBT, 2-(p-Methylaminophenyl)-7-(2-[18F]fluoroethoxy)imidazo-[2,1-b]benzothiazole, is a new selective PET tracer under clinical investigation to specifically image β-amyloid depositions (Aβ) in humans in-vivo that binds to Aβ with excellent affinity (Kd 0.7 ± 0.2) and high selectivity over tau and α-synuclein aggregates (Ki > 1000 nM). We aimed to characterize 18F-FIBT in a series of patients with different clinical-pathophysiological phenotypes and to compare its binding characteristics to the reference compound PiB. Six patients (mild late-onset and moderate early-onset AD dementia, mild cognitive impairment due to AD, intermediate likelihood, mild behavioral variant of frontotemporal dementia, subjective memory impairment without evidence of neurodegeneration, and mild dementia due to Posterior Cortical Atrophy) underwent PET imaging with 18F-FIBT on PET/MR. With the guidance of MRI, PET images were corrected for partial volume effect, time-activity curves (TACs) of regions of interest (ROIs) were extracted, and non-displaceable binding potentials (BPnd), standardized uptake value ratios (SUVR), and distribution volume ratio (DVR) were compared. Specific binding was detected in the cases with evidence of the AD pathophysiological process visualized in images of BPnd, DVR and SUVR, consistently with patterns of different tracers in previous studies. SUVR showed the highest correlation with clinical severity. The previous preclinical characterization and the results of this case series suggest the clinical usefulness of FIBT as a selective and highly affine next-generation 18F-labeled tracer for amyloid-imaging with excellent pharmacokinetics in the diagnosis of neurodegenerative diseases. The results compare well to the gold standard PiB and hence support further investigation in larger human samples.

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