Mental Health PET Radioligand Development (MHPRD) Program

A Program for Innovative PET Radioligand Development and Application - a translational toolbox for treatments for Mental Health (U01MH107803)

The National Institute of Mental Health (NIMH) has funded a grant to support the development of PET radioligands to probe high priority molecular targets implicated in mental illness. (U01MH107803).

The grant includes radiochemistry development, nonhuman primate evaluation, and translation to human studies. First awarded to Molecular Neuroimaging (MNI) in New Haven, CT, USA, the grant has moved cross-town to the Yale PET Center. All of the work on the grant, including radiochemistry preparation, nonhuman primate studies, and initial human evaluation and modeling analysis will be conducted at the Yale University PET Center and shared with the PET community.

PET imaging provides the opportunity to determine the brain distribution of the molecular target, to examine and distinguish target subtypes, to investigate the expression of the target in mental health disorders, and to demonstrate the target occupancy to determine an optimal therapeutic dose of potential therapeutic compounds. Developing tools to demonstrate target engagement is a crucial step in assessing compounds that may probe the pathobiology and/or provide novel therapies for mental health disorders.

Program Structure

Proposal Submissions: All members of the scientific community are invited to propose potential targets for radioligand development, with relevance to mental health. There are ample brain systems and mechanisms that are known or hypothesized to be highly relevant to mental illness.

Proposal Review: Proposed targets will be reviewed by both an external scientific committee (ESC) and a steering committee (SC), consisting of industry and academic subject-matter experts. Targets chosen for entrance into the radioligand development pipeline will proceed at one of the following tiers:

• Tier 1 - Chemistry development and in vitro testing
• Tier 2 - In vivo assessment in non-human primates
• Tier 3 - IND acquisition and human proof of concept and validation studies
• Tier 4 - Application to test mechanisms of action, assess brain penetrance, and target occupancy of drug candidates.

Once a target is chosen, Yale will receive funding through the NIMH grant to pursue tracer development. Depending on the existing data, radioligands may enter the development scheme at any tier if there is sufficient rationale that advancing the radioligand will inform relevant mental health disease mechanisms. Data collected will be shared with the scientific community.

For further clarifiaction on this chart, please contact Shannan Henry