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