Development of Novel PET Radioligands for PET Imaging Applications
Presenter: Lisa Wells, BSc Hons, Ph.D. | Head of Discovery CNS Applications, Invicro
The development and optimization of novel radioligands for drug development applications is critical to move new compounds from bench to bedside. However, in a similar manner to drug development, the process can carry risk.
By sharing the example of a novel radioligand development program for Sirtuin-2, using in vitro data to evaluate the level of target expression (maximum binding site, Bmax) and binding affinity (Kd), we assess whether the biological target will be tractable for an imaging study. Combining this knowledge with radiolabeling feasibility of the candidate radioligands and supportive in vitro characterization, biomathematical modelling methods are performed in order to identify the compounds that are amenable to PET/SPECT labeling and to rank them into likely successful candidates. Subsequent phases include radiolabeling of the chosen candidate(s), evaluation of the radioligand(s) in an appropriate preclinical species and translation into human. Here, we review the steps to reduce this attrition at an early stage, leading to a successful radioligand development program.
During this webinar, the presenter will:
- Provide an overview of a typical study design for the development of a suitable PET radioligand for a novel target in CNS disease models
- Explain the importance of determining target expression in the tissue(s) of interest and candidate ligand characteristics prior to in vivo imaging
- Explain how data is analyzed to answer “Morgan’s Pillars of Survival” for lead compounds in preclinical animal models, non-human primates and human subjects
