Development of [(124/125)I]IAZA as a New Proteinopathy Imaging Agent for Alzheimer’s Disease

Radioiodinated imaging agents for Aβ amyloid plaque imaging in Alzheimer’s disease (AD) patients have not been actively pursued. Our previous studies employed the “diaza” derivatives [(11)C]TAZA and [(18)F]flotaza in order to develop successful positron emission tomography (PET) imaging agents for Aβ plaques. There is a need for radioiodinated imaging agents for Aβ plaques for single photon emission computed tomography (SPECT) and PET imaging. We report our findings on the preparation of [(124/125)I]IAZA, a “diaza” analog of [(11)C]TAZA and [(18)F]flotaza, and the evaluation of binding to Aβ plaques in the postmortem human AD brain. The binding affinity of IAZA for Aβ plaques was Ki = 10.9 nM with weak binding affinity for neurofibrillary tangles (Ki = 3.71 μM). Both [(125)I]IAZA and [(124)I]IAZA were produced in >25% radiochemical yield and >90% radiochemical purity. In vitro binding of [(125)I]IAZA and [(124)I]IAZA in postmortem human AD brains was higher in gray matter containing Aβ plaques compared to white matter (ratio of gray to white matter was >7). Anti-Aβ immunostaining strongly correlated with [(124)/(125)I]IAZA in postmortem AD human brains. The binding of [(124)/(125)I]IAZA in postmortem human AD brains was displaced by the known Aβ plaque imaging agents. Thus, radiolabeled [(124/123)I]IAZA may potentially be a useful PET or SPECT radioligand for Aβ plaques in brain imaging studies.