Synthesis and evaluation of novel benzothiazole derivatives based on the bithiophene structure as potential radiotracers for β-amyloid plaques in Alzheimer's disease

In this study, six novel benzothiazole derivatives based on the bithiophene structure were developed as potential beta-amyloid probes. In vitro binding studies using A beta aggregates showed that all of them demonstrated high binding affinities with K-i values ranged from 0.11 to 4.64 nM. In vitro fluorescent staining results showed that these compounds can intensely stained A beta plaques within brain sections of APP/PS1 transgenic mice, animal model for AD. Two radioiodinated compounds [I-125]-2-(5'-iodo-2,2'-bithiophen-5-yl)-6-methoxybenzo[d]thiazole [I-125]10 and [I-125]-2-(2,2'-bithiophen-5-yl)-6-iodobenzo[d]thiazole [I-125]13 were successfully prepared through an iododestannylation reaction. Furthermore, in vitro autoradiography of the AD model mice brain sections showed that both [I-125]10 and [I-125]13 labeled the A beta plaques specifically with low background. In vivo biodistribution studies in normal mice indicated that [I-125]13 exhibited high brain uptake (3.42% ID/g at 2 min) and rapid clearance from the brain (0.53% ID/g at 60 min), while [I-125]10 showed lower brain uptake (0.87% ID/g at 2 min). In conclusion, these preliminary results of this study suggest that the novel radioiodinated benzothiazole derivative [I-125]13 may be a candidate as an in vivo imaging agent for detecting beta-amyloid plaques in the brain of AD patients. (C) 2010 Elsevier Ltd. All rights reserved.