Oligoethyleneoxy-Modified 99Mtc-Labeled Β-Amyloid Imaging Probes with Improved Brain Pharmacokinetics for Single-Photon Emission Computed Tomography.

An oligoethyleneoxy linker was introduced for conjugation between Tc-99m/Re-bis(aminoethanethiol) (BAT) and beta-amyloid (A beta) binding scaffolds. Rhenium complexes exhibited high to moderate binding affinity to A beta(1-42) aggregates and efficient fluorescent staining to A beta plaques in brain tissue. After radiolabeling, the Tc-99m-labeled probes revealed improved brain pharmacokinetics in normal ICR mice. Probe [Tc-99m]15 with potent binding affinity (K-i = 13.4 nM) and the highest initial brain uptake (2.10% ID/g at 2 min) in normal ICR mice was evaluated further. In vitro autoradiography showed specific labeling of A beta plaques by [Tc-99m]15 in transgenic (Tg) mouse brain tissue. Ex vivo autoradiography further demonstrated its efficient labeling of A beta plaques in a living Tg mouse. In vivo single photon emission computed tomography (SPECT)/CT imaging in six rhesus monkeys revealed remarkably improved brain uptakes (1.94-2.63% ID within 20 min) of [Tc-99m]15, making it highly potential to be used in humans for A beta plaques imaging in the brain.