Novel radioiodinated aurones as probes for SPECT imaging of beta-amyloid plaques in the brain.
We report a novel series of radioiodinated aurone derivatives as probes for imaging Abeta plaques in the brains of patients with Alzheimer's disease (AD) using single photon emission computed tomography (SPECT). In binding experiments in vitro, aurone derivatives showed very good affinity for Abeta aggregates (K(i) = 1.1 to 3.4 nM). No-carrier-added radioiodinated aurones were successfully prepared through an iododestannylation reaction from the corresponding tributyltin derivatives. In biodistribution experiments using normal mice, aurone derivatives displayed high brain uptake (1.7-4.5% ID/g at 2 min) and rapid clearance from the brain (0.1-0.4% ID/g at 30 min), especially [125I]15. Furthermore, a specific plaque labeling signal was observed in in vitro autoradiography of postmortem AD brain sections using [125I]15. [125I]15 may be a useful SPECT imaging agent for detecting Abeta plaques in the brain of AD.
Maya
Yoshifumi
Y
Department of Hygienic Chemistry, Graduate School of Biomedical Sciences, Nagasaki University, 1-14 Bunkyo-machi, Nagasaki 852-8521, Japan.
Ono
Masahiro
M
Watanabe
Hiroyuki
H
Haratake
Mamoru
M
Saji
Hideo
H
Nakayama
Morio
M
D000544:Alzheimer Disease / Q000175:diagnosis; D000818:Animals; D001345:Autoradiography; D001572:Benzofurans / Q000138:chemical synthesis / Q000493:pharmacokinetics*; D001921:Brain / Q000378:metabolism / Q000473:pathology; D007457:Iodine Radioisotopes; D051379:Mice; D058225:Plaque, Amyloid / Q000000981:diagnostic imaging*; D019275:Radiopharmaceuticals; D015899:Tomography, Emission-Computed, Single-Photon / Q000379:methods*
D001572:Benzofurans; D007457:Iodine Radioisotopes; D019275:Radiopharmaceuticals; C486837:aurone