Design, Synthesis, and Fluorescence Lifetime Study of Benzothiazole Derivatives for Imaging of Amyloids

The imaging of the distribution of beta-amyloid plaques in the brain is becoming an important diagnostic modality in Alzheimer's disease. The present study reports the synthesis of novel benzothiazole derivatives. The final products were characterized by spectral techniques such as FTIR, H-1 NMR, and electrospray ionization-mass spectrometry. The structure-activity relationship of these benzothiazole derivatives is also reported. The K-i values of these derivatives were evaluated by competitive binding assay studies. The analogs were labeled with Tc-99m for the potential diagnostic imaging of Alzheimer's disease using stannous chloride as a reducing agent. The radiochemical stability was found to be >= 90% for both the compounds and they were stable for 10-12 hours in human serum. Biodistribution studies of the Tc-99m complex in normal mice were performed after intravenous injection through the tail vein. The data showed high initial brain uptakes at 2 minutes (2.2% +/- 0.1% ID/g), and brain activities washed out to 0.3% +/- 0.02% ID/g at 6 hours. In conclusion, benzothiazole derivatives showed excellent binding affinities for beta-amyloid aggregates and high initial brain uptakes in normal mice.