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 99mTc/Re-bis(aminoethanethiol) (BAT) and β-amyloid (Aβ) binding scaffolds. Rhenium complexes exhibited high to moderate binding affinity to Aβ1–42 aggregates and efficient fluorescent staining to Aβ plaques in brain tissue. After radiolabeling, the 99mTc-labeled probes revealed improved brain pharmacokinetics in normal ICR mice. Probe [99mTc]15 with potent binding affinity (Ki = 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 Aβ plaques by [99mTc]15 in transgenic (Tg) mouse brain tissue. Ex vivo autoradiography further demonstrated its efficient labeling of Aβ 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 [99mTc]15, making it highly potential to be used in humans for Aβ plaques imaging in the brain.