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

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 ß-amyloid depositions (Aß) in humans in-vivo that binds to Aß 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.

Correction: 18F-FIBT may expand PET for ß-amyloid imaging in neurodegenerative diseases.

The author listing has been updated to indicate that Timo Grimmer and Kuangyu Shi are equally contributing authors.

Trends of patient referral to a memory clinic and towards earlier diagnosis from 1985-2009.

BACKGROUND: It may be assumed that increased public awareness of dementia due to Alzheimer's disease (AD) together with the availability of efficacious treatment will result in diagnostic evaluation at earlier stages of cognitive decline and diagnosis of dementia due to AD at earlier stages. METHODS: All persons that were examined at a university based memory clinic, in Germany, between 1985 and 2009 were included. RESULTS: In the 3,951 persons identified, linear regression analysis revealed a positive association between Mini Mental State Examination (MMSE) score and year of initial examination (yearIE) (ß = 0.266; p < 0.001). In the 1,821 patients diagnosed with dementia due to AD, a positive association between MMSE score and yearIE (ß = 0.230; p < 0.001) was revealed. MMSE scores were higher (ß = 0.195; p < 0.001) after the introduction of cholinesterase inhibitors in Germany in 1997. CONCLUSIONS: Diagnostic evaluation of individuals occurred at progressively earlier stages of cognitive decline. Dementia due to AD was diagnosed at progressively earlier stages, and this trend was associated with the availability of efficacious treatment. This is the first study on changes in patient referral and diagnosis based on a continuous 25 years period.