| First Author | Nguyen GAH | Year | 2022 |
| Journal | Molecules | Volume | 27 |
| Issue | 14 | PubMed ID | 35889425 |
| Mgi Jnum | J:349343 | Mgi Id | MGI:7642004 |
| Doi | 10.3390/molecules27144552 | Citation | Nguyen GAH, et al. (2022) [(124)I]IBETA: A New Abeta Plaque Positron Emission Tomography Imaging Agent for Alzheimer's Disease. Molecules 27(14) |
| abstractText | Several fluorine-18-labeled PET beta-amyloid (Abeta) plaque radiotracers for Alzheimer's disease (AD) are in clinical use. However, no radioiodinated imaging agent for Abeta 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 Abeta plaques using iodine-123 and iodine-125 are being pursued. In this study, we assess the iodine-124 radioiodinated pyridyl benzofuran derivative 5-(5-[124I]iodobenzofuran-2-yl)-N,N-dimethylpyridin-2-amine ([124I]IBETA) (Ki = 2.36 nM) for utilization in PET imaging for Abeta plaques. We report our findings on the radioiododestannylation reaction used to prepare [124/125I]IBETA and evaluate its binding to Abeta plaques in a 5 x FAD mouse model and postmortem human AD brain. Both [125I]IBETA and [124I]IBETA are produced in >25% radiochemical yield and >85% radiochemical purity. The in vitro binding of [125I]IBETA and [124I]IBETA in transgenic 5 x FAD mouse model for Abeta plaques was high in the frontal cortex, anterior cingulate, thalamus, and hippocampus, which are regions of high Abeta accumulation, with very little binding in the cerebellum (ratio of brain regions to cerebellum was >5). The in vitro binding of [125I]IBETA and [124I]IBETA in postmortem human AD brains was higher in gray matter containing Abeta plaques compared to white matter (ratio of gray to white matter was >5). Anti-Abeta immunostaining strongly correlated with [124/125I]IBETA regional binding in both the 5 x FAD mouse and postmortem AD human brains. The binding of [124/125I]IBETA in 5 x FAD mouse and postmortem human AD brains was displaced by the known Abeta plaque imaging agent, Flotaza. Preliminary PET/CT studies of [124I]IBETA in the 5 x FAD mouse model suggested [124I]IBETA was relatively stable in vivo with a greater localization of [124I]IBETA in the brain regions with a high concentration of Abeta plaques. Some deiodination was observed at later time points. Therefore, [124I]IBETA may potentially be a useful PET radioligand for Abeta plaques in brain studies. |
