Mental Health PET Radioligand Development (MHPRD) Program
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.
Target Proposal Submission
Please complete the proposal form and return it to the MHPRD Program at Yale: (mhprd@yale.edu).
Mental Health PET Radioligand Development (MHPRD) Program: Target Proposal Form
Once submitted, your proposal will be scheduled for evaluation by the External Scientific Committee (ESP), as well as the Project Steering Committee. These committees will review the submitted material, assess if the submitted work meets the goals of the project, and make a determination as to whether the target proposed will be approved for entrance into the radioligand development pipeline.
Program Review Committees
Steering Committee
People
Co-Principal Investigator
Professor of Radiology and Biomedical Imaging and of Biomedical Engineering; Director of Graduate Studies, Biomedical Engineering
Research Interests- Biomedical Engineering
- Nuclear Medicine
- Physiology
- Positron-Emission Tomography
- Radiology
Professor of Radiology and Biomedical Imaging; Director of Radiochemistry, PET Radiochemistry
Imaging Director
Associate Professor Adjunct; Associate Director of Imaging, Positron Emission Tomography (PET)
Research Interests- Stress Disorders, Post-Traumatic
- Substance Withdrawal Syndrome
- Alcohol-Related Disorders
- Neuroimaging
- Analytical, Diagnostic and Therapeutic Techniques and Equipment
Lead Chemist
Senior Research Scientist in Radiology and Biomedical Imaging; Associate Director of PET Center, Yale PET Center; Deputy Director of PET Center Chemistry Section; Director of Regulatory Affairs and Quality Control, Yale PET Center
Chemist
Associate Professor of Radiology & Biomedical Imaging and of Pharmacology
Research Interests- Positron-Emission Tomography
- Pharmacokinetics
- Pharmacology
- Biomarkers
- Chemistry, Pharmaceutical
- Alzheimer Disease
- Drug Development
- Drug Discovery
- Neurodegenerative Diseases
Lead Study Physician
Associate Professor of Radiology and Biomedical Imaging; Director, NeuroPET Imaging Program, Radiology and Biomedical Imaging; Medical Director, Yale Positron Emission Tomography (PET) Center
Research Interests- Autistic Disorder
- Mental Disorders
- Parkinson Disease
- Social Class
- Meditation
- Essential Tremor
- Molecular Imaging
- Frontotemporal Dementia
- Neuropsychiatry
- Neuroimaging
- Addiction Medicine
Study Physician
Assistant Professor of Psychiatry; Director, Yale Cocaine Research Clinic, Psychiatry; Associate Director of Clinical Affairs, Clinical Neuroscience Research Unit (CNRU), Psychiatry; Medical Director, Forensic Drug Diversion Clinic (ForDD)
PET data modeler
Research Scientist in Radiology and Biomedical Imaging
Research Interests- Data Analysis
- Brain
- Molecular Imaging
- Imaging, Three-Dimensional
- Positron-Emission Tomography
- Receptors, Neurotransmitter
- Whole Body Imaging
Publications and Presentations
Publications
Radiotracer | Target | Publication | Citation | Year |
---|---|---|---|---|
(R)-[18F]OF-Me-NB1, (S)-[18F]OF-Me-NB1 | NMDA GluN2B | Characterization in Non-Human Primates of (R)-[18F]OF-Me-NB1 and (S)-[18F]OF-Me-NB1 for Imaging the GluN2B Subunits of the NMDA Receptor DOI: 10.1007/s00259-022-05698-9 | Zheng MQ, Ahmed H, Smart K, Xu Y, Holden D, Kapinos M, Felchner Z, Haider A, Tamagnan G, Carson RE, Huang Y, Ametamey SM, Characterization in Non-Human Primates of (R)-[18F]OF-Me-NB1 and (S)-[18F]OF-Me-NB1 for Imaging the GluN2B Subunits of the NMDA Receptor, Eur J Nuc Med Mol Imag, epub, 2022 | 2022 |
(R)-[11C]NR2B-Me, (R)-[18F]OF-Me-NB1, and (S)-[18F]OF-NB1 | NMDA GluN2B | Comparison of three novel radiotracers for GluN2B-containing NMDA receptors in non-human primates: (R)-[11C]NR2B-Me, (R)-[18F]OF-Me-NB1, and (S)-[18F]OF-NB1 DOI: 10.1177/0271678X221084416 | Smart K, Zheng MQ, Ahmed H, Fanyi H, Xu Y, Cai L, Holden D, Kapinos M, Haider A, Felchner Z, Ropchan J, Tamagnan G, Innis RB, Pike VW, Ametamey SM, Huang Y, Carson RE, Comparison of three novel radiotracers for GluN2B-containing NMDA receptors in non-human primates: (R)-[11C]NR2B-Me, (R)-[18F]OF-Me-NB1, and (S)-[18F]OF-NB1, J Cereb Blood Flow Metabol, epub, 2022. | 2022 |
(rac)-18F OF-NB1, (R)-18F OF-NB1, and (S)-18F OF-NB1 | NMDA GluN2B | Evaluation of (rac)-18F OF-NB1, (R)-18F OF-NB1,and (S)-18F OF-NB1 for the imaging of GluN2B subunit containing NMDA receptors in nonhuman primates. | Ahmed H, Zheng MQ, Smart K, Fang H, Zhang L, Emery PR, Gao H, Ropchan J, Haider A, Tamagnan G, Carson RE, Ametamy SM, Huang Y, Evaluation of (rac)-18F OF-NB1, (R)-18F OF-NB1,and (S)-18F OF-NB1 for the imaging of GluN2B subunit containing NMDA receptors in nonhuman primates, J Nucl Med, in press. | 2022 |
[18F]MNI-968 and [18F]MNI-800 | D1 | Dopamine D1 Receptor Agonist PET Tracer Development: Assessment in Nonhuman Primates. DOI:10.2967/jnumed.120.256008 | Barret O, Zhang L, Alagille D, Constantinescu CC, Sandiego C, Papin C, Sullivan JM, Morley T, Carroll VM, Seibyl J, Chen J, Lee C, Villalobos A, Gray D, McCarthy TJ, Tamagnan G. Dopamine D1 Receptor Agonist PET Tracer Development: Assessment in Nonhuman Primates. J Nucl Med. 2021 Sep 1;62(9):1307-1313. doi: 10.2967/jnumed.120.256008 . Epub 2021 Feb 12. | 2021 |