Abstract |
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 [11C]TAZA and [18F]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 [124/125I] IAZA, a “diaza” analog of [11C]TAZA and [18F]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 [125I] IAZA and [124I] IAZA were produced in >25% radiochemical yield and >90% radiochemical purity. In vitro binding of [125I] IAZA and [124I] 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 [124/125I] IAZA in postmortem AD human brains. The binding of [124/125I] IAZA in postmortem human AD brains was displaced by the known Aβ plaque imaging agents. Thus, radiolabeled [124/123I] IAZA may potentially be a useful PET or SPECT radioligand for Aβ plaques in brain imaging studies.
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Authors | Thrisha T Reddy, Michael H Iguban, Lusine L Melkonyan, Jasmine Shergill, Christopher Liang, Jogeshwar Mukherjee |
Journal | Molecules (Basel, Switzerland)
(Molecules)
Vol. 28
Issue 2
(Jan 15 2023)
ISSN: 1420-3049 [Electronic] Switzerland |
PMID | 36677925
(Publication Type: Journal Article)
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Chemical References |
- Iodine-125
- Iodine-124
- iodoazomycin arabinoside
- Iodine Radioisotopes
- Amyloid beta-Peptides
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Topics |
- Humans
- Alzheimer Disease
(diagnostic imaging, metabolism)
- Iodine Radioisotopes
(metabolism)
- Positron-Emission Tomography
(methods)
- Brain
(diagnostic imaging, metabolism)
- Plaque, Amyloid
(diagnostic imaging, metabolism)
- Amyloid beta-Peptides
(metabolism)
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