Title: Development of second generation of molecular imaging probes for Amyloid beta
Speaker: Dr.Chongzhao Ran (Massachusetts General Hospital/Harvard Medical School)
Venue: Room 102, Building 6, University Town Campus
Time: Oct 16, Tuesday, 9:30
Amyloid beta (Ab) deposits and Tau tangles are the two characteristic biomarkers for Alzheimer’s disease (AD). In the progression of AD, various Ab subtypes, including soluble and insoluble Abs, co-exist, but soluble Abs are the dominant species at the pre-symptomatic stage. Studies show that soluble Aβs such as oligomers are more neurotoxic than insoluble deposits (fibrils and plaques) and can serve as biomarkers for the pre-symptomatic stages of AD. Notably, recent evidence indicates that Aβ species are the key initiator for AD pathology; therefore, for early/pre-symptomatic imaging, Aβs are the very ideal targets. Additionally, it is well-established that abnormal levels of Abs in the brain appear 30 years before symptom starts in humans. However, the current probes (the first generation (1stG)) can only detect the abnormal Ab deposits around 5 years before the clinical syndrome, leaving a 25-year gap between the early pathogenesis and the imaging detection. In the past years, my research group has been focusing on developing 2ndG (second generation) imaging probes, which are defined as probes that are highly sensitive for both soluble and insoluble Abs and can be used to fill the 25-year gap that cannot be reported by the 1stG probes.
Most of the 1stG tracers are based on the scaffold of thioflavin and styrene, whose intrinsic limitations are their insensitivity to soluble Abs, the high toxicity species and likely biomarkers for the pre-symptomatic stage. To overcome the intrinsic limitation of the 1st G probe, we have systematically investigated near infrared fluorescent (NIRF) curcuminoids as the new scaffold for detecting Abs. In this presentation, I will also discuss our tracer design half-curcuminoids as the novel second generation of PET tracers for Abs. With the optimized PET tracers, we will discuss results from preclinical PET imaging with mice. For a long term, we will advance the probes for future translational studies.
Announced by School of Matreials Science and Engineering