# Development of next generation of α2δ-1 PET tracers for neuroimaging

> **NIH NIH K99** · MASSACHUSETTS GENERAL HOSPITAL · 2022 · $91,102

## Abstract

Abstract/summary
PET imaging can be potentially used to quantify biochemical processes underlying pain and drug addiction
mechanisms at molecular level by detecting the expression level of α2δ-1 receptor. Due to the low CNS
permeability of the first generation of α2δ-1 PET tracers (see preliminary data), the lesion cannot be detected by
PET imaging. This proposal is focused on the development of the next generation of α2δ-1 PET tracers, which
are expected to show high CNS uptake and be more suitable for neuroimaging. In order to achieve the high CNS
permeability, two categories of tracers, namely trans-4-[18F]fluorogabapentin prodrug (Aim 1A) and novel
pyrazolopyridazine α2δ-1 radiotracer (Aim 1B), are proposed. The proposed PET tracers will be first screened
in heathy mice. The promising candidates with good CNS permeability and pharmacokinetic properties will be
fully characterized in health rats, and healthy non-human primates (NHPs) (Aim 2). We will also explore the
applications of newly designed tracers in animal models of pain and animal models of drug addiction such as
spinal nerve ligation (SNL) rats and ethanol dependence mice, respectively (Aim 3). We hypothesize these
tracers will show moderate to high CNS permeability and enable the detection of PET signal changes that
correlate with the neuropathic pain and drug addiction progression. The proposed project will provide necessary
data for a future clinical study.

## Key facts

- **NIH application ID:** 10507390
- **Project number:** 1K99EB033407-01
- **Recipient organization:** MASSACHUSETTS GENERAL HOSPITAL
- **Principal Investigator:** Yu-Peng ZHOU
- **Activity code:** K99 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2022
- **Award amount:** $91,102
- **Award type:** 1
- **Project period:** 2022-08-15 → 2024-06-30

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/10507390

## Citation

> US National Institutes of Health, RePORTER application 10507390, Development of next generation of α2δ-1 PET tracers for neuroimaging (1K99EB033407-01). Retrieved via AI Analytics 2026-05-25 from https://api.ai-analytics.org/grant/nih/10507390. Licensed CC0.

---

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