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Article

New Diphenylacetylenes as Probes for Positron Emission Tomographic Imaging of Amyloid Plaques

Supporting Info

Rajesh Chandra,^† Shunichi Oya,^† Mei-Ping Kung,^† Catherine Hou,^† Lee-Way Jin,^‡ and Hank F. Kung*^†^§

Departments of Radiology and Pharmacology, University of Pennsylvania, Philadelphia, Pennsylvania 19104, and Department of Pathology, University of California Health System, Sacramento, California 95817

J. Med. Chem., 2007, 50 (10), pp 2415–2423

DOI: 10.1021/jm070090j

Publication Date (Web): April 21, 2007

†

Department of Radiology, University of Pennsylvania.

‡

Department of Pathology, University of California Health System.

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

Department of Pharmacology, University of Pennsylvania.

Abstract

A series of ¹⁸F fluoropegylated diphenylacetylenes as probes for binding to Aβ plaques were successfully prepared. These relatively rigid acetylenes, 12a, 12b, 14a, and 14b, displayed high binding affinities in postmortem AD brain homogenates (K_i ranging from 1.2 to 2.9 nM). In vivo biodistribution in normal mice exhibited excellent initial brain penetrations (4.42, 4.55, 5.41, and 6.78% dose/g at 2 min for [¹⁸F]12a, 12b, 14a, and 14b, respectively). [¹⁸F]12b and [¹⁸F]14b, with a longer fluoropegylated unit, that is, n = 3, showed faster brain washout at 30 min postinjection (0.42 and 1.57% dose/g) as compared to the shorter fluoropegylated chain ligands, that is, [¹⁸F]12a and [¹⁸F]14a (1.03 and 3.69% dose/g). Autoradiography and homogenate binding confirmed the high binding signal due to Aβ plaques. These preliminary results suggest that the novel diphenylacetylenes may be potentially useful for imaging of Aβ plaques in the brain of patients with Alzheimer's disease.