Linking Tau PET to Medial Temporal Lobe Subregions With High Resolution MRI

The investigators will conduct a tau PET scan in cognitively normal older adults and patients with Mild Cognitive Impairment (MCI), enrolled in the National Alzheimer's Coordinating Center (NACC) study at the University of Pennsylvania's Penn Memory Center/Alzheimer's Disease Core Center (PMC/ADC).

Study Overview

• Status: Active, not recruiting
• Conditions: Mild Cognitive Impairment
• Intervention / Treatment: Drug: 2-(2-([18F]fluoro)pyridin-4-yl)-9H-pyrrolo[2,3-b:4,5-c']dipyridine

Detailed Description

This is a cross-sectional and longitudinal study using the radiotracer [18F]-PI-2620 to determine the relationship of tau pathology to both cross-sectional and longitudinal clinical and biomarker data of NACC cohort participants who are Cognitively Normal or MCI. All subjects will already be part of the longitudinal cohort study, known as the "NACC" cohort, of the PMC/ADC (protocol 068200). Participants will provide informed consent for this protocol before beginning any study procedures. After screening assessments, participants will undergo PET scan imaging with [18F]PI-2620. There will be one follow-up [18F]PI-2620 PET scan approximately 18 +/- 6 months after bas eline scan.

• Study Type: Observational
• Enrollment (Estimated): 150

Contacts and Locations

Study Locations

• United States
  • Pennsylvania
    • Philadelphia, Pennsylvania, United States, 19104
      • University of Pennsylvania, School of Medicine

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 56 years and older (Adult, Older Adult)
• Accepts Healthy Volunteers: Yes

• Sampling Method: Non-Probability Sample

Study Population

Adults cognitively normal or Mild Cognitive Impairment (MCI) or Alzheimer's Disease.

Description

Inclusion Criteria:

• Males and females ≥ 60 years of age.
• Part of the NACC longitudinal cohort (IRB# 068200) of the PMC/ADCC with consensus conference designation of cognitively normal or Mild Cognitive Impairment (MCI) or Alzheimer's Disease (AD) Possible or Probable.
• NACC longitudinal visit completed or scheduled within 6 months before or after enrollment in this study.
• Women must be post-menopausal or surgically sterile.
• An amyloid PET scan, completed as a part of the NACC protocol (IRB# 825943), must be performed or scheduled within 12 months before or after the [18F]PI-2620 PET scan.
• A brain MRI, completed as a part of NACC protocol (IRB# 068200), must be performed or scheduled within 6 months before or after the [18F]PI-2620 PET scan. Scan should be of adequate research quality, including 3 Tesla and/or 7 Tesla high-resolution imaging of MTL structure.

Exclusion Criteria:

• Have any medical or psychiatric conditions that, in the opinion of the investigator, would compromise the subject's safety or successful participation in the study.
• Have evidence of structural abnormalities such as major stroke or mass on MRI that is likely to interfere with analysis of the PET scan.
• Inability to tolerate or contraindication to imaging procedures in the opinion of an investigator or treating physician.
• Have a history of significant or ongoing alcohol abuse or substance abuse or dependence based on medical record review or self-reported.

The inclusion / exclusion criteria will be ascertained through self-report in conjunction with any medical history available through the participant's medical or research records (EPIC or the ADC database)

Study Plan

How is the study designed?

Design Details

• Observational Models: Cohort
• Time Perspectives: Prospective

Number of groups / cohorts

2

Cohorts and Interventions

Group / Cohort	Intervention / Treatment
Cognitively Normal Older Adults; Subjects will receive an IV bolus injection of approximately 5 mCi ± 20% of [18F]PI-2620. All subjects will undergo a 30-minute brain PET/CT scan performed starting at approximately 45 minutes' post injection of [18F]PI-2620. A low-dose CT scan will be acquired according to standard PET/CT imaging procedures to be used for attenuation correction. All images will be reconstructed using standard reconstruction techniques	Drug: 2-(2-([18F]fluoro)pyridin-4-yl)-9H-pyrrolo[2,3-b:4,5-c']dipyridine; A small molecule aimed for binding and PET-imaging of aggregated tau protein in the human brain.; Other Names: [18F]PI-2620
Mild Cognitively Impaired Older Adults or Older Adults with Alzheimer's Disease; Subjects will receive an IV bolus injection of approximately 5 mCi ± 20% of [18F]PI-2620. All subjects will undergo a 30-minute brain PET/CT scan performed starting at approximately 45 minutes' post injection of [18F]PI-2620. A low-dose CT scan will be acquired according to standard PET/CT imaging procedures to be used for attenuation correction. All images will be reconstructed using standard reconstruction techniques	Drug: 2-(2-([18F]fluoro)pyridin-4-yl)-9H-pyrrolo[2,3-b:4,5-c']dipyridine; A small molecule aimed for binding and PET-imaging of aggregated tau protein in the human brain.; Other Names: [18F]PI-2620

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Correlation between PI-2620 SUVR and MTL subregion thickness	Correlation between cross-sectional PI-2620 standard uptake value ratio (SUVR) and MTL subregion thickness (mm) in both controls and MCI/AD.	Baseline
Interaction between PI-2620 SUVR and amyloid status prediction of MTL subregion thickness	Interaction between cross-sectional PI-2620 standard uptake value ratio (SUVR) and amyloid status for prediction of MTL subregion thickness (mm) in both controls and MCI/AD.	Baseline
Correlation between longitudinal PI-2620 SUVR and MTL subregion thickness	Correlation between longitudinal PI-2620 standard uptake value ratio (SUVR) and MTL subregion thickness (mm) in both controls and MCI/AD.	18-24 months
Interaction between longitudinal PI-2620 SUVR and amyloid status for prediction of MTL subregion thickness	Interaction between longitudinal PI-2620 standard uptake value ratio (SUVR) and amyloid status for prediction of MTL subregion thickness (% annual change) in both controls and MCI/AD.	18-24 months

Collaborators and Investigators

• Sponsor: University of Pennsylvania
• Collaborators: National Institutes of Health (NIH)
• Investigators: Principal Investigator: David Wolk, MD, University of Pennsylvania

Study record dates

Study Major Dates

• Study Start (Actual): March 11, 2020
• Primary Completion (Estimated): January 1, 2027
• Study Completion (Estimated): January 1, 2027

Study Registration Dates

• First Submitted: January 3, 2020
• First Submitted That Met QC Criteria: January 29, 2020
• First Posted (Actual): January 31, 2020

Study Record Updates

• Last Update Posted (Estimated): September 5, 2025
• Last Update Submitted That Met QC Criteria: September 4, 2025
• Last Verified: September 1, 2025

More Information

Terms related to this study

• Additional Relevant MeSH Terms: Mental Disorders; Neurocognitive Disorders; Cognition Disorders; Cognitive Dysfunction; ((18)F)PI-2620
• Other Study ID Numbers: 833864

Drug and device information, study documents

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