Kinetic modeling of Florbetaben (BAY 94-9172) binding to β-amyloid in human brains using one and two input functions

Objectives Florbetaben is a [18F]-labeled stilbene derivative which has great potential to detect β-amyloid in the living human brain. To investigate the influence of a possible metabolite passing the blood brain barrier, a kinetic modeling approach with two input functions was applied.

Methods After i.v. administration of ~300 MBq Florbetaben, 10 subjects with Alzheimer's disease (AD) and 10 age-matched healthy volunteers (HV) underwent 3D-PET. Concentrations of parent compound and metabolites were determined in plasma and used as input functions. VOI-based tissue-activity curves (TACs) from 25 brain regions were analyzed using two tissue compartments with one input function (OIF) or three tissue compartments with two input functions (TIF) over a time range of 90 (OIF) and 200 (TIF) minutes. Also the reference tissue approach MRTM3 was applied. The kinetics of the metabolite(s) was described by one tissue compartment ("simplified" K1 fixed). DVR, BP_P and SUV-ratio were used to characterize specific binding (reference: cerebellar cortex). Effect size in group comparison was determined by Cohen's d.

Results All TACs could be analyzed by the OIF- and TIF-approach with similar precision. Kinetic parameters associated with β-amyloid load were significantly higher in ADs compared to HVs, e.g. for the mean of frontal, lateral temporal, parietal and posterior cingulate cortices (AD n=8, HV n=9, with decreasing order of d) OIF: DVR=1.75±0.13 vs 1.28±0.11, d= 4.23; MRTM3: DVR=1.54±0.07 vs 1.18±0.11, d=4.11; SUV-ratio (70-90 min)=1.79±0.14 vs 1.30±0.12, d=4.03; OIF: BP_P=4.60±1.45 vs 1.44±0.45, d=3.22; TIF: DVR=2.62±0.89 vs 1.34±0.21, d=2.82; BP_P=4.27±2.05 vs 0.91±0.45, d=2.52.

Conclusions For Florbetaben, DVRs computed with MRTM3 and SUV-ratios are parameters well suited to quantify β-amyloid deposition by means of PET.

Research Support This trial was supported by Bayer Healthcare Berlin (Germany)