# Molecular Chemiluminescence Probes for Imaging of Amyloid beta in Animal Models

> **NIH NIH R01** · MASSACHUSETTS GENERAL HOSPITAL · 2024 · $823,551

## Abstract

The highly exciting results from the recent clinical trial of Lecanemab for Alzheimer’s disease (AD) reignite
tremendous enthusiasm for AD drug development. Lecanemab is the first drug to meet all the clinical endpoints
without controversy over the past decades. However, compared to other diseases like cancer, the progress in
AD drug development, both in clinical and preclinical stages, lags behind. The number of AD therapeutics under
preclinical discovery is unquestionably dwarfed by the number of cancer drugs at similar stages. Several high-
throughput imaging methods, such as bioluminescence imaging, have significantly accelerated drug discovery
for cancer research. However, such a high-throughput imaging method is not readily available for AD drug
discovery. In this proposal, we plan to develop “smart” (turn-on) chemiluminescence probes that can enable
high-throughput imaging for preclinical AD research.
 “Smart” (turn-on) fluorescence imaging has been routinely used for in vitro, cellular, and in vivo imaging. In
contrast, the exploration of smart chemiluminescence imaging has been limited due to its low sensitivity and
dependence on reactive oxygen species (ROS) or enzyme activity. To address these challenges, we have
developed a novel chemiluminescence probe called ADLumin-1. Through extensive validation, we have
confirmed that ADLumin-1 exhibits turn-on chemiluminescence upon interaction with amyloid beta (Aβ) species,
resulting in a remarkable 216-fold increase in intensity in vitro. Notably, ADLumin-1 does not rely on ROS or
enzyme activity, distinguishing it from other chemiluminescence probes. In vivo two-photon imaging indicated
that ADLumin-1 was highly specific for Ab deposits. In vivo whole-brain imaging showed that ADLumin-1
provided a 1.80-fold higher signal from 5-month-old transgenic AD (5xFAD) mice than that from the age-matched
wild-type mice. Our recent study has further shown that ADLumin-1 enables high-throughput chemiluminescence
imaging, as evidenced by imaging 30 mice within 30 minutes with a $100 imaging fee in a longitudinal therapeutic
study. Additionally, our preliminary results have showcased the feasibility of optical 3D brain imaging using our
chemiluminescence probe, opening up incredible possibilities for future AD research.
 This proposal aims to advance the development of ADLumin-X probes through in vitro and in vivo validation,
with the ultimate objective of employing the most effective probe for high-throughput monitoring of therapeutic
interventions in experimental AD drug studies. Our overarching goal is to offer accessible, highly sensitive, and
cost-effective “PET-like” optical imaging methods for expediting preclinical AD drug development.

## Key facts

- **NIH application ID:** 10884628
- **Project number:** 1R01AG083759-01A1
- **Recipient organization:** MASSACHUSETTS GENERAL HOSPITAL
- **Principal Investigator:** Chongzhao Ran
- **Activity code:** R01 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2024
- **Award amount:** $823,551
- **Award type:** 1
- **Project period:** 2024-06-01 → 2029-03-31

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/10884628

## Citation

> US National Institutes of Health, RePORTER application 10884628, Molecular Chemiluminescence Probes for Imaging of Amyloid beta in Animal Models (1R01AG083759-01A1). Retrieved via AI Analytics 2026-05-25 from https://api.ai-analytics.org/grant/nih/10884628. Licensed CC0.

---

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