Effects of Adolescent Synaptic Pruning (SPA PET)

The study will use a PET-based measure of brain cell (neuron) connections (synapses) in young adults who have also obtained an MRI, to assess how the loss of brain cell connections (synaptic pruning) is captured by MRI-based measures. This will inform youth MRI studies to understand neurotypical brain development that can help identify abnormal trajectories as in mental illness.

Study Overview

• Status: Enrolling by invitation
• Conditions: Healthy Adult Participants; Synaptic Plasticity
• Intervention / Treatment: Radiation: PET Imaging Scan using [11C]UCB-J

Detailed Description

The loss of brain cell (neuron) connections (synapses) through human development, known as synaptic pruning, has been characterized in postmortem studies but how this proceeds in live humans as they age into adulthood is not well understood. This study will use the PET tracer [11C]UCB-J which provides a direct measure of synaptic density, in conjunction with previously acquired ultra-high field MRI, in a group of young adults in order to understand how standard MRI-based measures reflect changes in the density of synapses. PET [11C]UCB-J is known to measure the density of synaptic connections by measuring a protein (SV2A) present in synapses. A comparison of results from the current study with MRI-based measures of byproducts of synaptic membrane breakdown from childhood to early adulthood will allow assessment of how non-invasive MRI reflects synaptic pruning through development, facilitating studies of how the brain changes through adolescence and into adulthood, which is needed to identify patterns of development associated with the emergence of mental illness.

• Study Type: Interventional
• Enrollment (Estimated): 60
• Phase: Not Applicable

Contacts and Locations

Study Locations

• United States
  • Pennsylvania
    • Pittsburgh, Pennsylvania, United States, 15213
      • Laboratory of Neurocognitive Development

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: Adult; Older Adult
• Accepts Healthy Volunteers: Yes

Description

Inclusion Criteria:

• Males or females between 18-26 years of age, AND currently enrolled in the Parent Project (R01MH067924)

Exclusion Criteria: (these exclusion criteria are outlined in the Parent Project)

• Head injury with loss of consciousness over an hour.
• A vision problem or eye movement problem (such as lazy eye, double vision, blurred vision, or color blindness).
• A learning disability and/or ever had an Individualized Education Plan (IEP) in school.
• Significant neurological or metabolic illness: Epilepsy, Meningitis, Encephalitis, Diabetes, Huntington's disease.
• Diagnosed with a psychiatric disorder.
• Participants with, or with a first degree relative, having a DSM IV Axis l psychiatricdisorder.
• Metal implants or ferromagnetic objects contained within the body which may interfere with the MRI scan (but not limited to, those with a pacemaker, presence of metallic fragments near the eyes or spinal cord, or cochlear implant.) Dental fillings do not present a risk for MRI. If there is a possibility of metal being present in the participant's body, the participant will be excluded from the study.
• Weight more than 250 pounds.
• Claustrophobia or uncomfortable in small spaces.
• <70% on the Achenbach scale (either from Youth Self Report (YSR) or Adult Self Report (ASR)).
• IQ < 80 or IQ > 130.
• Pregnancy or lactation, lack of effective birth control during 15 days before the scans.
• Currently employed as radiation worker; or participation in radioactive drug research protocols within the previous year such that the total cumulative annual radiation dose (i.e., from participation in the previous radioactive drug study [studies] and this study) would exceed the radiation dose limits specified in the FDA regulations (i.e., 21 CFR 361.1) that govern the research use of [C-11]UCB-J
• History of drug or alcohol abuse (from parent study eligibility).

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Basic Science
• Allocation: N/A
• Interventional Model: Single Group Assignment
• Masking: None (Open Label)

Number of Arms

1

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: PET Imaging Supplemental Component; Adult participants enrolled in the parent study, will be given the option to be a part of the PET imaging supplemental project. Maximum enrollment is 60 adult participants. Interested participants will be consented into the PET portion, and will have a single PET scan (as outlined in the Study Description section).	Radiation: PET Imaging Scan using [11C]UCB-J; [11C]UCB-J (~ 15 mCi and ≤ 6μg) will be injected as a slow intravenous bolus. Following an intravenous bolus injection of [11C]UCB-J, the participants will be positioned in the scanner for a low dose CT scan (for attenuation correction) fifty-five minutes after the [11C]UCB-J injection, and emission data will be collected.

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Non-invasive quantification of synaptic pruning	1. Age-related changes in synaptic density through young adulthood o Cross-sectional age-related (18-26 years of age) changes in synaptic density via SUVR quantified within the dorsolateral prefrontal cortex.	The PET-CT scan will be within approximately 30 days of the parent study MRI.
Non-invasive quantification of synaptic pruning	2. Within-subject associations of synapse density to MRI-derived measures of brain membrane byproducts o Synaptic density, based on SUVR modeling of [11C]UCB-J acquisitions, will be compared to ultra-high field (7 Tesla) [31P]MRSI measurement of membrane phospholipid levels obtained from the same participants.	The PET-CT scan will be within approximately 30 days of the parent study MRI.

Collaborators and Investigators

• Sponsor: Beatriz Luna
• Collaborators: National Institute of Mental Health (NIMH)
• Investigators: Principal Investigator: Beatriz Luna, PhD, University of Pittsburgh

Study record dates

Study Major Dates

• Study Start (Actual): January 9, 2026
• Primary Completion (Estimated): June 30, 2028
• Study Completion (Estimated): June 30, 2028

Study Registration Dates

• First Submitted: April 27, 2026
• First Submitted That Met QC Criteria: May 4, 2026
• First Posted (Actual): May 6, 2026

Study Record Updates

• Last Update Posted (Actual): May 6, 2026
• Last Update Submitted That Met QC Criteria: May 4, 2026
• Last Verified: May 1, 2026

More Information

Terms related to this study

• Keywords: PET Imaging
• Additional Relevant MeSH Terms: 1-((3-(methylpyridin-4-yl)methyl)-4-(3,4,5-trifluorophenyl)pyrrolidin-2-one
• Other Study ID Numbers: STUDY24060023; 3R01MH067924-19S1 (U.S. NIH Grant/Contract)

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: YES
• IPD Plan Description: Individual [11C]UCB-J SUVR maps will be shared via the NIH Data Archive (NDA), along with basic corresponding demographic data (age, sex).
• IPD Sharing Time Frame: Upon completion of the study.
• IPD Sharing Access Criteria: Access of shared IPD is managed by the NIH Data Archive.
• IPD Sharing Supporting Information Type: STUDY_PROTOCOL

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: No
• Studies a U.S. FDA-regulated device product: No