Study Of Tc-99m Labled Benzothiazole Aniline Complex For Aβ Imaging

Alzheimer's disease(AD) is a neurodegenerative disease of the brain. With the aging population, AD is becoming one of the serious problems for human health and living quality. Currently, the only definitive diagnosis of AD is to anatomize the postmortem brain. So it is important to study fast and fewer wound inspect methods.Aβis one of the important character in AD pathology, and is strongly associated with the pathogenesisi of the disease.The investigation of molecular imaging probes targeting Aβare useful to the diagnosis of AD and evaluation of the effects of AD treatment as well as the study of AD pathology.It was reported that benzothiazole aniline (BTA) derivatives showed affinity with Aβ. Therefore, novel 99mTc-labeled benzothiazole aniline complexs were designed and synthesized in this thesis. The detailed studies are as follows.1. Design of the target compounds of 99mTc-labeled benzothiazole aniline complexes and their synthetic routesIn order to increase the affinity for Aβand brain uptakes, 99mTc-BTA0-5-BAT,99mTc-BTA2-5-MAMA and 99mTc-BTNB-5-MAMA were designed by modifying 99mTc-labeled benzothiazole aniline complexe compound 99mTc-BTA0-5-MAMA. Moreover, the synthetic routes of the above complexes were also designed.2. Synthesis of the precursors of 99mTc-labeled benzothiazole aniline complexes The precursors of designed complexes 99mTc-BTA2-5-MAMA, 99mTc-BTNB-5-MAMA and 99mTc-BTA0-5-MAMA were synthsised. The synthesis of BTA0-5-MAMA-MBz was tried by reduction of BTA0-5-MAMA-MBz. The synthetic routes of 99mTc-BTA0-5-MAMA-MBz was designed.3. Preparation of 99mTc-labeled benzothiazole aniline complexes 99mTc-BTA2-5-MAMA, 99mTc-BTNB-5-MAMA and 99mTc-BTA0-5-MAMA were prepared.The radio-chemical purities(RCP) of 99mTc-BTA2-5-MAMA and 99mTc-BTA0-5-MAMA wre higher than 99%.4. Investigation of the physical chemical properties and biodistribution of 99mTc-labeled benzothiazole aniline complexesThe logP value of the 99mTc-BTA2-5-MAMA was tested. The biodistribution of 99mTc-BTA2-5-MAMA was performed. Furthermore, poly(butylcyanoacrylate) (PBCA) nanoparticles (NP) wit the size of 210 nm were prepared. The biodistribution of 99mTc-BTA0-5-MAMA loaded NP in mice was investigated.