Developing a cassette microdosing approach to enhance the throughput of PET imaging agent screening

This study designed a cassette microdose with LC–MS/MS method to enhance the throughput for screening radiopharmaceutical biodistribution in the rat brain directly. Three unradiolabeled compounds (FPBM FPBM2 and AV-133) were chosen as model drugs administrated intravenously to the rats as a cassette as opposed to discrete study. The rat brain biodistribution data, target localization, the differential uptake ratio (%ID/g) and the brain tissue-specific binding ratio were obtained by the LC–MS/MS analysis. These data matched very well with the values obtained by the standard radioactivity measurements. Moreover, no significant differences between discrete dosing and cassette dosing were observed. By circumventing the need for radiolabeled molecules, this method may be high-throughput and safe for the research and development of new PET imaging agents. The combination of cassette microdosing and LC–MS/MS would be a medium throughput screening tool at an early stage in the discovery/development process of PET imaging agents. Graphical abstract
Source: Journal of Pharmaceutical and Biomedical Analysis - Category: Drugs & Pharmacology Source Type: research