Novel styrylpyridines as probes for SPECT imaging of amyloid plaques.
We report a series of radioiodinated styrylpyridines as single photon emission computed tomography probes for imaging Abeta plaques in the brain of patients with Alzheimer's disease (AD). In vitro binding showed that all of the styrylpyridines displayed very good binding affinities in postmortem AD brain homogenates (Ki = 3.6 to 15.5 nM). No-carrier-added samples of 13a, 13b, 16a, 16b, and 16e (radioiodinated with 125I) were successfully prepared. The in vivo biodistribution in normal mice, at 2 min after injection, showed excellent initial brain penetrations (4.03, 6.22, 5.43, and 8.04% dose/g for [125I]13a, 13b, 16a, and 16b, respectively). Furthermore, in vitro autoradiography of AD brain sections showed that the high binding signal was specifically due to the presence of Abeta plaques. Taken together, these results strongly suggest that these styrylpyridines are useful for imaging Abeta plaques in the living human brain.
Qu
Wenchao
W
Department of Radiology and Pharmacology, University of Pennsylvania, Philadelphia, Pennsylvania 19104, USA.
Kung
Mei-Ping
MP
Hou
Catherine
C
Benedum
Tyler E
TE
Kung
Hank F
HF
D000544:Alzheimer Disease / Q000000981:diagnostic imaging*; D016229:Amyloid beta-Peptides / Q000378:metabolism; D000818:Animals; D001345:Autoradiography; D001667:Binding, Competitive; D001921:Brain / Q000000981:diagnostic imaging* / Q000378:metabolism; D002460:Cell Line; D006801:Humans; D007457:Iodine Radioisotopes; D008297:Male; D051379:Mice; D008813:Mice, Inbred ICR; D058225:Plaque, Amyloid / Q000378:metabolism*; D011725:Pyridines / Q000138:chemical synthesis* / Q000737:chemistry / Q000493:pharmacokinetics; D011869:Radioligand Assay; D019275:Radiopharmaceuticals / Q000138:chemical synthesis* / Q000737:chemistry / Q000493:pharmacokinetics; D013329:Structure-Activity Relationship; D013343:Styrenes / Q000138:chemical synthesis* / Q000737:chemistry / Q000493:pharmacokinetics; D014018:Tissue Distribution; D015899:Tomography, Emission-Computed, Single-Photon
D016229:Amyloid beta-Peptides; D007457:Iodine Radioisotopes; D011725:Pyridines; D019275:Radiopharmaceuticals; D013343:Styrenes