Synthesis and evaluation of [11C]PBD150, a radiolabeled glutaminyl cyclase inhibitor for the potential detection of Alzheimer's disease prior to amyloid β aggregation

Allen F Brooks; Isaac M Jackson; Xia Shao; George W Kropog; Phillip Sherman; Carole A Quesada; Peter J H Scott

doi:10.1039/C5MD00148J

Synthesis and evaluation of [¹¹C]PBD150, a radiolabeled glutaminyl cyclase inhibitor for the potential detection of Alzheimer's disease prior to amyloid β aggregation

Medchemcomm. 2015 Jun 1;6(6):1065-1068. doi: 10.1039/C5MD00148J.

Authors

Allen F Brooks¹, Isaac M Jackson¹, Xia Shao¹, George W Kropog¹, Phillip Sherman¹, Carole A Quesada¹, Peter J H Scott²

Affiliations

¹ Division of Nuclear Medicine, Department of Radiology, The University of Michigan Medical School, 2276 Medical Science I Building, Ann Arbor, Michigan 48109, USA.
² Division of Nuclear Medicine, Department of Radiology, The University of Michigan Medical School, 2276 Medical Science I Building, Ann Arbor, Michigan 48109, USA ; The Interdepartmental Program in Medicinal Chemistry, The University of Michigan, 428 Church St., Ann Arbor, Michigan 48109, USA.

Abstract

The phenol of 1-(3-(1H-imidazol-1-yl)propyl)-3-(4-hydroxy-3-methoxyphenyl)thiourea was selectively carbon-11 labelled to generate [¹¹C]PBD150 in 7.3% yield from [¹¹C]methyl triflate (non-decay corrected; radiochemical purity ≥95%, specific activity = 5.7 Ci/µmol, n=5). Evaluation of [¹¹C]PBD150 by small animal PET imaging (mouse and rat) determined it does not permeate the blood brain barrier, indicating previously described therapeutic effect in transgenic mice was likely not the result of inhibiting central nervous system glutaminyl cyclase.

Abstract

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