^99mTc-labeled Small Molecules for Diagnosis of Alzheimer’s Disease: Past, Recent and Future Perspectives

Background: Alzheimer’s disease (AD) is an age-related progressive neurodegenerative disease. Its prominent hallmarks are extracellular deposition of β-amyloids (amyloid plaques), intracellular neurofibrillary tangles (NTFs), neurodegeneration and finally loss of cognitive function. Hence, AD diagnosis in the early stage and monitoring of the disease are of great importance. Methods: In this review article, we have reviewed recent efforts for design, synthesis and evaluation of 99mTc labeled small molecule for AD imaging purposes. Results: These small molecules include derivatives of Congo red, benzothiazole, benzofuran, benzoxazole, naphthalene, biphenyl, chalcone, flavone, aurone, stilbene, curcumin, dibenzylideneacetone, quinoxaline, etc. The different aspects of 99mTc-labeled small molecules including chemical structure, their affinity toward amyloid plaques, BBB permeation and in vivo/vitro stability will be discussed. Conclusion: The findings of this review confirm the importance of 99mTc-labeled small molecules for AD imaging. Future studies based on the pharmacophore of these designed compounds are needed for improvement of these molecules for clinical application.