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Protein aggregation is the principal component of numerous protein misfolding pathologies termed proteinopathies, such as Alzheimer’s disease, Parkinson’s disease, prion disease, and AA amyloidosis with unmet treatment needs. Protein aggregation inhibitors have great potential for the prevention and treatment of proteinopathies. Here we report the development of an automated real-time microliter-scale high throughput screening (MSHTS) system for amyloid aggregation inhibitors using quantum-dot nanoprobes. Screening 504 crude extracts and 134 low molecular weight aromatic compounds revealed the relationship of amyloid-β (Aβ) aggregation inhibitory activities of plant extracts using a plant-based classification. Within the eudicots, rosids, Geraniales and Myrtales showed higher activity. Screening low molecular weight aromatic compounds demonstrated that the structure of tropolone endows it with potential Aβ aggregation inhibitory activity. The activity of the most active tropolone derivative was higher than that of rosmarinic acid. MSHTS also identified three chaperone molecules as tau aggregation inhibitors. These results demonstrate that our automated MSHTS system is a novel and robust tool that can be adapted to a wide range of compounds and aggregation-prone polypeptides.

In an Asian international multicenter phase II trial conducted in patients with peripheral T-cell lymphoma (PTCL), [F-18]FDG-PET/CT was used for evaluation of the therapeutic response. Standardization of the PET/CT scanners was necessary before patient enrollment. We therefore standardized the scanners by phantom tests based on the profile approved by the Quantitative Imaging Biomarkers Alliance (QIBA) of Radiological Society of North America (RSNA). The tests were conducted on 12 scanners in 12 facilities in compliance with the QIBA Profile and used National Electrical Manufacturers Association (NEMA) International Electrotechnical Commission (IEC) body phantoms. We measured three parameters (standardized uptake value [SUV], resolution and noise) and adjusted the imaging parameter values. The indexes recommended in the Japanese Society of Nuclear Medicine (JSNM) guideline were also evaluated. In a total of 12 facilities, 6 facilities required no change in imaging conditions and 6 facilities required changes in imaging parameters. After revision, the three measurements (SUV, resolution and noise) met QIBA criteria at all sites, but 10 of the 12 scanners did not meet JSNM criteria. We standardized imaging conditions using phantoms as required in the RSNA-QIBA profile for response evaluation by [F-18]FDG PET/CT images in a multicenter study.