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Article

Novel Styrylpyridines as Probes for SPECT Imaging of Amyloid Plaques

Supporting Info

Wenchao Qu,^† Mei-Ping Kung,^† Catherine Hou,^† Tyler E. Benedum,^‡ and Hank F. Kung*^†^§

Departments of Radiology and Pharmacology, University of Pennsylvania, Philadelphia, Pennsylvania 19104, and Avid Radiopharmaceuticals, Inc., Philadelphia, Pennsylvania 19104

J. Med. Chem., 2007, 50 (9), pp 2157–2165

DOI: 10.1021/jm070025+

Publication Date (Web): April 6, 2007

†

Department of Radiology, University of Pennsylvania.

‡

Avid Radiopharmaceuticals, Inc.

To whom correspondence should be addressed. Hank F. Kung, Ph.D., Department of Radiology, University of Pennsylvania, 3700 Market Street, Room 305, Philadelphia, Pennsylvania 19104. Tel.: (215) 662-3096. Fax: (215) 349-5035. E-mail: kunghf@sunmac.spect.upenn.edu.

Department of Pharmacology, University of Pennsylvania.

Abstract

We report a series of radioiodinated styrylpyridines as single photon emission computed tomography probes for imaging Aβ 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 (K_i = 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 Aβ plaques. Taken together, these results strongly suggest that these styrylpyridines are useful for imaging Aβ plaques in the living human brain.