# PET PROBES FOR IMAGING THE VESICULAR ACETYLCHOLINE TRANSPORTER

> **NIH NIH R01** · WASHINGTON UNIVERSITY · 2020 · $586,784

## Abstract

A. Project Summary/Abstract
Vesicular acetylcholine transporter (VAChT) is a reliable biomarker for studying the loss of cholinergic neurons
and synapses. Cholinergic deficits are associated with impairment in memory, motor function and cognitive
functions. A PET tracer for clinical imaging of VAChT will provide a critical noninvasive tool to measure
cholinergic deficits and assess disease severity of patients with Alzheimer disease, Parkinson disease,
progressive supranuclear palsy (PSP) and other dementias. It can also be used to monitor the efficacy of
cholinergic therapies in neurological diseases. Under our previously funded R01 for the discovery of PET
imaging agents for imaging the VAChT, we developed [18F]VAT and [11C]TZ659. Both have high potency (Ki ≤
1.0 nM) and selectivity for VAChT versus sigma receptors (>1000-fold) and showed promise in rodent and
nonhuman primate studies. More importantly, by the end of the five year funding period, we completed imaging
dosimetry studies in nonhuman primates, rodent toxicity studies, and the SOP for automated production of
[18F]VAT in our cGMP facilities. Approval of our eIND, IRB and RDRC applications for [18F]VAT enabled a pilot
PET imaging in eight healthy human subjects that demonstrated: (a) high reproducibility and reliability of
[18F]VAT production in the cGMP facility; (b) no observable adverse effects in research subjects; (c) high
specificity for the VAChT-enriched striatal region with target: non-target ratio of 6.0; and (d) favorable kinetic
with high striatal accumulation 20 min post-injection, and rapid washout from non-target cerebellar hemispheres.
Therefore, the goal of this R01 renewal is to focus on translational studies of [18F]VAT in healthy control subjects
to provide key measures of radiation dosimetry, variability within and between subjects, age-dependence and
sex-dependence. These validation studies will provide the basis for future investigations of pathologic
conditions. In addition, we will use nonhuman primates pre-treated with a D2 dopamine receptor agonist or
antagonist to investigate their impact on brain VAChT expression assessed by PET with [18F]VAT. Finally, we
will determine the feasibility of quantitatively imaging VAChT in patients with PSP-RS and compare the in vivo
PET findings to in vitro autoradiography studies using [3H]VAT for postmortem brain tissues from cases with
autopsy proven PSP.

## Key facts

- **NIH application ID:** 9930641
- **Project number:** 5R01NS075527-09
- **Recipient organization:** WASHINGTON UNIVERSITY
- **Principal Investigator:** Zhude Tu
- **Activity code:** R01 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2020
- **Award amount:** $586,784
- **Award type:** 5
- **Project period:** 2011-06-15 → 2022-05-31

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/9930641

## Citation

> US National Institutes of Health, RePORTER application 9930641, PET PROBES FOR IMAGING THE VESICULAR ACETYLCHOLINE TRANSPORTER (5R01NS075527-09). Retrieved via AI Analytics 2026-05-24 from https://api.ai-analytics.org/grant/nih/9930641. Licensed CC0.

---

*[NIH grants dataset](/datasets/nih-grants) · CC0 1.0*