18F-AV-1451 High Resolution Autopsy Study

NCT02350634 | Completed Phase 1 Results

• 1 other identifier: 18F-AV-1451-A13
• Study Type: interventional
• Target: 3
• Locations: 1 country
• Sites: 2

Brief Summary

The study is designed to examine the relationship between imaging results detected on a 18F-AV-1451 PET scan and pathology found at autopsy within six months of imaging.

Conditions

Alzheimer's Disease

Outcome Measures

Primary Outcomes (7)

• Relationship of Flortaucipir Scan and Pathology - Whole Cortical Composite Region

  Correlation between flortaucipir standard uptake value ratio (SUVr) and neuropathology at autopsy. SUVr measurements for the analysis consisted of whole cortical global quantitation of the PET scan from 82 FreeSurfer-defined regions of interest (ROIs). Values were normalized to the brainstem to obtain the SUVr. Neuropathology was measured by immunohistology using AT8 antibody. Spearman correlation coefficient was calculated. Spearman correlation coefficients range from -1 to +1. A value of -1 indicates perfect negative correlation, and a value of +1 indicates a perfect positive correlation.

  autopsy within 6 months of scan

• Relationship of Flortaucipir Scan and Pathology - Frontal Composite Region

  Correlation between flortaucipir standard uptake value ratio (SUVr) and neuropathology at autopsy. SUVr measurements for the analysis consisted of frontal composite region quantitation of the PET scan regions of interest (ROIs). Values were normalized to the brainstem to obtain the SUVr. Neuropathology was measured by immunohistology using AT8 antibody. Spearman correlation coefficient was calculated. Spearman correlation coefficients range from -1 to +1. A value of -1 indicates perfect negative correlation, and a value of +1 indicates a perfect positive correlation.

  autopsy within 6 months of scan

• Relationship of Flortaucipir Scan and Pathology - Parietal Composite Region

  Correlation between flortaucipir standard uptake value ratio (SUVr) and neuropathology at autopsy. SUVr measurements for the analysis consisted of parietal composite region quantitation of the PET scan regions of interest (ROIs). Values were normalized to the brainstem to obtain the SUVr. Neuropathology was measured by immunohistology using AT8 antibody. Spearman correlation coefficient was calculated. Spearman correlation coefficients range from -1 to +1. A value of -1 indicates perfect negative correlation, and a value of +1 indicates a perfect positive correlation.

  autopsy within 6 months of scan

• Relationship of Flortaucipir Scan and Pathology - Cingulate Composite Region

  Correlation between flortaucipir standard uptake value ratio (SUVr) and neuropathology at autopsy. SUVr measurements for the analysis consisted of cingulate composite region quantitation of the PET scan regions of interest (ROIs). Values were normalized to the brainstem to obtain the SUVr. Neuropathology was measured by immunohistology using AT8 antibody. Spearman correlation coefficient was calculated. Spearman correlation coefficients range from -1 to +1. A value of -1 indicates perfect negative correlation, and a value of +1 indicates a perfect positive correlation.

  autopsy within 6 months of scan

• Relationship of Flortaucipir Scan and Pathology - Temporal Composite Region

  Correlation between flortaucipir standard uptake value ratio (SUVr) and neuropathology at autopsy. SUVr measurements for the analysis consisted of temporal composite region quantitation of the PET scan regions of interest (ROIs). Values were normalized to the brainstem to obtain the SUVr. Neuropathology was measured by immunohistology using AT8 antibody. Spearman correlation coefficient was calculated. Spearman correlation coefficients range from -1 to +1. A value of -1 indicates perfect negative correlation, and a value of +1 indicates a perfect positive correlation.

  autopsy within 6 months of scan

• Relationship of Flortaucipir Scan and Pathology - Occipital Composite Region

  Correlation between flortaucipir standard uptake value ratio (SUVr) and neuropathology at autopsy. SUVr measurements for the analysis consisted of occipital composite region quantitation of the PET scan regions of interest (ROIs). Values were normalized to the brainstem to obtain the SUVr. Neuropathology was measured by immunohistology using AT8 antibody. Spearman correlation coefficient was calculated. Spearman correlation coefficients range from -1 to +1. A value of -1 indicates perfect negative correlation, and a value of +1 indicates a perfect positive correlation.

  autopsy within 6 months of scan

• Relationship of Flortaucipir Scan and Pathology - Limbic Composite Region

  Correlation between flortaucipir standard uptake value ratio (SUVr) and neuropathology at autopsy. SUVr measurements for the analysis consisted of limbic composite region quantitation of the PET scan regions of interest (ROIs). Values were normalized to the brainstem to obtain the SUVr. Neuropathology was measured by immunohistology using AT8 antibody. Spearman correlation coefficient was calculated. Spearman correlation coefficients range from -1 to +1. A value of -1 indicates perfect negative correlation, and a value of +1 indicates a perfect positive correlation.

  autopsy within 6 months of scan

Study Arms (1)

Autopsy Cohort

EXPERIMENTAL

End-of-life subjects (life expectancy \< 6 months) consenting to brain donation at autopsy. Subjects will receive a single IV bolus injection of 370 MBq(10 mCi) of flortaucipir F18.

Drug: Flortaucipir F18

Interventions

Flortaucipir F18 DRUG

Subjects will receive a single IV bolus injection of 370 megabecquerel (MBq) (10 millicurie \[mCi\]) of flortaucipir.

Also known as: [F-18]T807, 18F-AV-1451

Autopsy Cohort

Eligibility Criteria

• Age: 60 Years - 89 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• Projected life expectancy ≤ 6 months

You may not qualify if:

• Primary brain tumor, known metastases to the brain, central nervous system lymphoma
• Major, focal structural brain lesion
• Aggressively being treated with life sustaining measures
• Clinically significant infectious disease
• History of risk factors for Torsades de Pointes or are currently taking medication known to cause QT prolongation
• Have received or participated in a trial with investigational medications in the past 30 days
• Females of childbearing potential who are pregnant or not using adequate contraception

Sponsors & Collaborators

• Avid Radiopharmaceuticals: lead

Study Sites (2)

Banner Alzheimer's Institute

Phoenix, Arizona, 85006, United States

Location

University of California, San Francisco

San Francisco, California, 94121, United States

Location

Related Publications (1)

• Ushizima D, Chen Y, Alegro M, Ovando D, Eser R, Lee W, Poon K, Shankar A, Kantamneni N, Satrawada S, Junior EA, Heinsen H, Tosun D, Grinberg LT. Deep learning for Alzheimer's disease: Mapping large-scale histological tau protein for neuroimaging biomarker validation. Neuroimage. 2022 Mar;248:118790. doi: 10.1016/j.neuroimage.2021.118790. Epub 2021 Dec 20.

  PMID: 34933123 BACKGROUND

MeSH Terms

Conditions

Alzheimer Disease

Interventions

7-(6-fluoropyridin-3-yl)-5H-pyrido(4,3-b)indole

Condition Hierarchy (Ancestors)

Dementia; Brain Diseases; Central Nervous System Diseases; Nervous System Diseases; Tauopathies; Neurodegenerative Diseases; Neurocognitive Disorders; Mental Disorders

Limitations and Caveats

The original intent of the protocol was to assess relationships between in vivo flortaucipir PET signal and tau pathology at a higher resolution than the Free Surfer ROIs, such as voxel-wise. Higher resolution could potentially offer more precise insights into tracer distribution patterns. However, the analysis was constrained by challenges in acquiring a complete set of pathology images from collaborators and unanticipated technical challenges in image processing.

Results Point of Contact

• Title: Medical Director
• Organization: Avid Radiopharmaceuticals, Inc.

AVD_Clinical_Ops@lists.lilly.com

215-298-0700

Study Officials

• Medical Director

  Avid Radiopharmaceuticals, Inc.

  STUDY DIRECTOR

Publication Agreements

• PI is Sponsor Employee: No
• Restrictive Agreement: Yes

Study Design

• Study Type: interventional
• Phase: phase 1
• Allocation: NA
• Masking: NONE
• Purpose: DIAGNOSTIC
• Intervention Model: SINGLE GROUP
• Sponsor Type: INDUSTRY
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: January 8, 2015
• First Posted: January 30, 2015
• Study Start: November 26, 2016
• Primary Completion: June 16, 2017
• Study Completion: June 16, 2017
• Last Updated: June 10, 2025
• Results First Posted: June 10, 2025

Record last verified: 2025-05

Locations

US (2)