# Tau Imaging with [F-18]AV-1451: Considerations for Performance across the Spectrum of Disease Severity

> **NIH NIH P01** · UNIVERSITY OF PITTSBURGH AT PITTSBURGH · 2020 · $290,301

## Abstract

Project-4 Summary/Abstract:
 Much enthusiasm has centered on the recently developed positron emission
tomography (PET) radiotracers designed to be selective for tau deposits. Initial results are encouraging in that
these compounds bind to Alzheimer's disease (AD) brain in a manner consistent with tau pathology. However,
several important questions remain for all of the tau tracers including: 1) the spectrum of tau pathology to which
they bind (i.e., AD vs. non-AD tau deposits); 2) the identity of off-target (non-tau) binding; and 3) the accuracy of
commonly used analysis methods across the full spectrum of severity of tau pathology. The first two issues are
best addressed by postmortem studies and we will address these in Project-3. The latter issue is best addressed
by in vivo pharmacokinetic studies and we will do that in Project-4. The key issue addressed in Project-4 is whether
the commonly employed short acquisition time (i.e., 80-100 min after bolus injection of [F-18]AV-1451) followed by
analysis using tissue ratios (TR) yields values directly proportional to the number of tau binding sites across
the full range of pathology. This proportionality requires a steady-state period during which a “stable” measure of
TR can be obtained. There is evidence that this may not be true for [F-18]AV-1451 - especially at the high-end of
tau pathology (see preliminary data). We will address this issue by using the same detailed, fully dynamic (FD)
pharmacokinetic analysis approach that we used to characterize PiB. The FD method does not rely on equilibrium
between compartments (i.e., tissues or blood), but instead obtains quantitative binding measures by fitting a
pharmacokinetic model (with arterial blood as input) to the tissue kinetics allowing accurate quantitation of tracer
binding across the full spectrum of pathology. Thus, the FD method can serve as a standard of truth to assess
the veracity of simplified methods. In Project-4, we will compare FD measures with 80-100 min bolus-TR measures
across a wide range of [F-18]AV-1451 retention levels to determine if the bolus-TR method accurately reflects tau
load at the high-end. We will also use the FD data to generate: 1) a simplified reference tissue model (SRTM) and
2) parameters for a bolus-plus-constant-infusion (B+I) method – a technique to achieve stable TR when a bolus
injection cannot. We will then determine whether the SRTM and B+I measures approximate FD measures better
than bolus-TR. Because arterial FD methods are not routinely performed, even in research centers, we will attempt
to translate the findings from our FD analysis to improved and widely-applicable methods by identifying: 1) a
mathematical correction for the bolus-TR outcome measure; 2) a SRTM with improved performance relative to
bolus-TR; and 3) a B+I method also with improved performance. We will study this same phenomenon in 24-month
change in tracer retention. While we use [F-18]AV-1451 in Projects-1 and -2 in a way that is ...

## Key facts

- **NIH application ID:** 9927990
- **Project number:** 5P01AG025204-15
- **Recipient organization:** UNIVERSITY OF PITTSBURGH AT PITTSBURGH
- **Principal Investigator:** WILLIAM E KLUNK
- **Activity code:** P01 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2020
- **Award amount:** $290,301
- **Award type:** 5
- **Project period:** — → 2022-04-30

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/9927990

## Citation

> US National Institutes of Health, RePORTER application 9927990, Tau Imaging with [F-18]AV-1451: Considerations for Performance across the Spectrum of Disease Severity (5P01AG025204-15). Retrieved via AI Analytics 2026-05-27 from https://api.ai-analytics.org/grant/nih/9927990. Licensed CC0.

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