sup 99m^Tc-Labeled 2-Arylbenzothiazoles: A[Beta] Imaging Probes with Favorable Brain Pharmacokinetics for Single-Photon Emission Computed Tomography

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 A... aggregates (K^sub i^ < 50 nM) for ^sup 99m^Tc labeling and further evaluation. The ^sup 99m^Tc-labeled probes showed good affinity and specificity to A... plaques in Tg mouse brain tissue in in vitro autoradiography studies. Moreover, [^sup 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 A... plaques by [^sup 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 ^sup 99m^Tc-labeled A... probes. The semiquantitative data showed that [^sup 99m^Tc]14b penetrated the brains of rhesus monkeys. These results indicate that [^sup 99m^Tc]14b could be utilized as a SPECT imaging probe for A... plaques. (ProQuest: ... denotes formulae/symbols omitted.)