Novel 99mTc-2-arylimidazo[2,1-b]benzothiazole derivatives as SPECT imaging agents for amyloid-β plaques.

Six novel 2-arylimidazo[2,1-b]benzothiazole (IBT) derivatives were synthesized as potential tridentate radiotracers for AD imaging purposes. Two of these ligands (6a,b) were successfully labeled with 99mTc radionuclide at high radiochemical purity using fac-[99mTc(CO)3(H2O)3]+ synthon. [99mTc]7a and [99mTc]7b were evaluated as single photon emission computed tomography (SPECT) imaging agents for Aβ plaque in AD. [99mTc]7a and [99mTc]7b exhibited suitable affinity toward Aβ aggregates with IC50 values of 33.2 and 102.5 nM, respectively. The IC50 value of these radiotracers depends on the length of the spacer (alkyl chain). In biodistribution study, these complexes showed good initial brain uptakes (0.78 and 0.86% ID/g at 2 min post-injection) and fast blood clearance. Autoradiography results confirmed that these small 99mTc complexes (Mw about 600 Da) can bind to Aβ plaques in the brain sections of the rat AD model. Histopathological staining with Congo red approved the presence of Aβ plaques in these brain sections.