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

The phenol of 1-(3-(1H-imidazol-1-yl)propyl)-3-(4-hydroxy-3-methoxyphenyl)thiourea was selectively carbon-11 labelled to generate [C]PBD150 in 7.3% yield from [C]methyl triflate (non-decay corrected; radiochemical purity ≥95%, specific activity = 5.7 Ci/µmol, n=5). Evaluation of [C]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.