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(99m)Tc-Labeled 2-Arylbenzothiazoles: Aβ Imaging Probes with Favorable Brain Pharmacokinetics for Single-Photon Emission Computed Tomography.
Bioconjugate Chemistry 2016 October 8
A series of 2-arylbenzothiazole derivatives conjugated with bis(aminoethanethiol) (BAT) chelating groups were designed and synthesized. A competitive binding assay-based screening was used to select seven rhenium complexes with potent binding affinity toward Aβ1-42 aggregates (Ki < 50 nM) for (99m)Tc labeling and further evaluation. The (99m)Tc-labeled probes showed good affinity and specificity to Aβ plaques in Tg mouse brain tissue in in vitro autoradiography studies. Moreover, [(99m)Tc]14b exhibited favorable brain pharmacokinetics in normal mice (2.11% ID/g at 2 min and 0.62% ID/g at 60 min). Ex vivo autoradiography revealed extensive labeling of Aβ plaques by [(99m)Tc]14b in the brain of Tg mice. Furthermore, we performed the first single-photon emission computed tomography (SPECT) imaging study in nonhuman primates with (99m)Tc-labeled Aβ probes. The semiquantitative data showed that [(99m)Tc]14b penetrated the brains of rhesus monkeys. These results indicate that [(99m)Tc]14b could be utilized as a SPECT imaging probe for Aβ plaques.
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