[124I]IBETA: A New Aβ Plaque Positron Emission Tomography Imaging Agent for Alzheimer's Disease

Several fluorine-18-labeled PET beta-amyloid (A beta) plaque radiotracers for Alzheimer's disease (AD) are in clinical use. However, no radioiodinated imaging agent for A beta plaques has been successfully moved forward for either single-photon emission computed tomography (SPECT) or positron emission tomography (PET) imaging. Radioiodinated pyridyl benzofuran derivatives for the SPECT imaging of A beta plaques using iodine-123 and iodine-125 are being pursued. In this study, we assess the iodine-124 radioiodinated pyridyl benzofuran derivative 5-(5-[I-1(24)]iodobenzofuran2-yl)-N,N-dimethylpyridin-2-amine ([I-124]BETA) (Ki = 2.36 nM) for utilization in PET imaging for A13 plaques. We report our findings on the radioiododestannylation reaction used to prepare [[I-124]BETA and evaluate its binding to A beta plaques in a 5 x FAD mouse model and postmortem human A beta brain. Both [I-125]IBETA and [(124/)(125I)]IBETA are produced in >25% radiochemical yield and >85% radiochemical purity. The in vitro binding of [ I-125]IBETA and [1241, JIBETA in transgenic 5 x FAD mouse model for A beta plaques was high in the frontal cortex, anterior cingulate, thalamus, and hippocampus, which are regions of high A beta accumulation, with very little binding in the cerebellum (ratio of brain regions to cerebellum was >5). The in vitro binding of [I-125]IBETA and [I-124]IBETA in postmortem human AD brains was higher in gray matter containing A13 plaques compared to white matter (ratio of gray to white matter was >5). Anti-A beta immunostaining strongly correlated with [(124)/I-125]IBETA regional binding in both the 5 x FAD mouse and postmortem AD human brains. The binding of [(124)/I-125]IBETA in 5 x FAD mouse and postmortem human AD brains was displaced by the known A beta plaque imaging agent, Flotaza. Preliminary PET/CT studies of [I-124]IBETA in the 5 x FAD mouse model suggested [I-124]IBETA was relatively stable in vivo with a greater localization of [I-124]IBETA in the brain regions with a high concentration of A beta plaques. Some deiodination was observed at later time points. Therefore, [I-124]IBETA may potentially be a useful PET radioligand for A beta plaques in brain studies.

Automated summary

This study evaluated the use of iodine-124 radioiodinated pyridyl benzofuran derivative in PET imaging of A13 plaques and reported the results of binding experiments in vitro and in vivo.