# Development of a Novel PET Tracer for Imaging Microglial Function in Alzheimer's Disease

> **NIH NIH F30** · STANFORD UNIVERSITY · 2023 · $40,363

## Abstract

SUMMARY
Alzheimer’s disease (AD) is the most common form of dementia and a major cause of death in adults over 65.
Unfortunately, advancements in early diagnosis and treatment development have been hindered by a paucity of
sensitive biomarkers enabling detection of early, functionally relevant, neuromolecular changes: Although data
from genome wide association studies have revealed genes relating to a loss of healthy innate immune function
as a major risk factor for AD, there remains a need for biomarkers to investigate neuro-immune function
preceding and during the development of this disease. Positron Emission Tomography (PET) is an extremely
sensitive molecular imaging modality well suited to studying such biomarkers, with established utility for non-
invasive in vivo interrogation of biochemical processes. Existing PET biomarkers of neuroinflammation (e.g., the
translocator protein 18 kDa [TSPO], CB2, CSF1R, P2X7) suffer from significant drawbacks including a poorly
elucidated functional role and/or expression across multiple cell types in the central nervous system (CNS).
Within the CNS, the adenosine diphosphate receptor P2Y12R is expressed exclusively on microglia, the innate
immune effector cells of the CNS, and drives chemotaxis and morphological changes associated with microglial
activation. Generally considered a biomarker of homeostatic microglia, P2Y12 expression has been
demonstrated to decrease in both acute (e.g., lipopolysaccharide challenge) and chronic (e.g., AD)
neuroinflammation. Postmortem human brain tissue from advanced AD patients demonstrated a global
reduction in P2Y12R expression and a near total absence of P2Y12R expression on microglia surrounding
amyloid-beta plaques. Despite being an extremely well characterized pharmacological target, there are currently
no CNS-penetrable P2Y12R PET tracers. Aiming to address this unmet need, I identified clinical drug candidate
AZD1283 as a promising possible PET tracer. Recently, I devised a strategy to radiolabel this molecule with
carbon-11 (t1/2=20.4 min), synthesized [11C]AZD1283 and showed it to be highly stable in vitro in human plasma.
Here, I will compare [11C]AZD1283 with TSPO PET tracer [11C]DPA-713 for their ability to measure alterations
in microglia in two murine models of neuroinflammation (Aim 1). Additionally, I will assess the translational
potential of [11C]AZD1283 through imaging healthy non-human primates and in vitro autoradiography of human
AD brain tissue (Aim 2). The experience gained by pursuing these aims will allow me to develop a skillset directly
applicable to future independent research developing tracers and therapies that target the immune system. I will
conduct this work under the mentorship of Michelle James, PhD, a world expert in neuroinflammation PET, with
additional mentorship from Thomas Montine, MD, PhD, the chair of Pathology at Stanford. Their mentorship, in
conjunction with the excellent training environment and resources available to m...

## Key facts

- **NIH application ID:** 10834001
- **Project number:** 5F30AG074633-02
- **Recipient organization:** STANFORD UNIVERSITY
- **Principal Investigator:** Isaac Mackenzie Jackson
- **Activity code:** F30 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2023
- **Award amount:** $40,363
- **Award type:** 5
- **Project period:** 2022-09-09 → 2024-09-08

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/10834001

## Citation

> US National Institutes of Health, RePORTER application 10834001, Development of a Novel PET Tracer for Imaging Microglial Function in Alzheimer's Disease (5F30AG074633-02). Retrieved via AI Analytics 2026-05-24 from https://api.ai-analytics.org/grant/nih/10834001. Licensed CC0.

---

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