Abstract
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 99mTc labeling and further evaluation. The 99mTc-labeled probes showed good affinity and specificity to Aβ plaques in Tg mouse brain tissue in in vitro autoradiography studies. Moreover, [99mTc]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 [99mTc]14b in the brain of Tg mice. Furthermore, we performed the first single-photon emission computed tomography (SPECT) imaging study in nonhuman primates with 99mTc-labeled Aβ probes. The semiquantitative data showed that [99mTc]14b penetrated the brains of rhesus monkeys. These results indicate that [99mTc]14b could be utilized as a SPECT imaging probe for Aβ plaques.
Original language | English (US) |
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Pages (from-to) | 2493-2504 |
Number of pages | 12 |
Journal | Bioconjugate chemistry |
Volume | 27 |
Issue number | 10 |
DOIs | |
State | Published - Oct 19 2016 |