Skip to Main Content

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)
PET imagery crop

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

Novel Target Development Tiers

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.

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
  • 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

Pressentations

Radiotracer Target Presentation Conference Year
[18F]GATT-34 and
[18F]GATT-44
GAT-1 Development of Novel Brain-Penetrant Radioligands for PET Imaging of GABA Transporter-1 SNMMI 2021
[18F]GATT-34 and
[18F]GATT-44
GAT-1 Kinetic modeling of novel radiotracers for the GABA Transporter-1 in nonhuman primates SNMMI 2021
(R)-18F-OF-Me-NB1 NMDA
GluN2B
Assessment of (R)-18F-OF-Me-NB1 as a potential radiotracer for PET Imaging of the NMDA GluN2B subunit in the monkey brain SNMMI 2021
(R)-18F-OF-Me-NB1,
(S)-18F-OF-NB1,
(R)-11C-NR2B-Me
NMDA
GluN2B
In vivo comparison of three novel radiotracers for the NMDA receptor GluN2B subunit in non-human primates SNMMI 2021
(R)-18F-OF-NB1,
(S)-18F-OF-NB1
NMDA
GluN2B
Radiosynthesis and Evaluation of (R)- and (S)-18F-OF-NB1 for imaging the GluN2B subunits of the NMDA receptor in non-human primates SNMMI 2021
(R)-18F-OF-NB1,
(S)-18F-OF-NB1,
(±)-18F-OF-NB1
NMDA
GluN2B
Radiosynthesis and Evaluation in non-human primates of novel 18F-labeled radioligands for imaging the GluN2B subunit of the NMDA receptor SNMMI 2020
(S)-18F-OF-Me-NB1,
(R)-18F-OF-Me-NB1,
(R)-11C-OF-Me-NB1
NMDA
GluN2B
Radiosynthesis and Characterization in non-Human Primates of Three Enantiomerically Pure PET Radioligands for Imaging the GluN2B Subunit of the NMDA Receptor Complex SNMMI 2020
[18F]Bavarostat HDAC6 Assessment of HDAC6 PET radiotracer 18F-Bavarostat SNMMI 2020
[18F]MNI-968 D1 In vivo characterization of an agonist dopamine D1 receptors tracer [18F]MNI-968 (PF-06730110) in human ACNP 2017