# Development of sensitive PET tracers of pan-Amyloid-beta species for Alzheimer's disease

> **NIH NIH R01** · MASSACHUSETTS GENERAL HOSPITAL · 2024 · $826,732

## Abstract

The recent FDA approval of Leqembi (Lecanemab) for Alzheimer’s disease (AD) has spurred great optimism,
and this approval also likely opens a door for preventive treatment for AD. However, currently available PET
tracers have limited capacity for this preventive purpose. More sensitive new PET tracers are highly desirable.
Amyloid beta (A), is an appealing AD biomarker, as significant initial deposits of A precede Tau pathology.
Accordingly, the 2018 A/T/N Research Framework published by NIA-AA (National Institute of Ageing and
Alzheimer’s Association) suggests that As are the earliest biomarkers for AD before the appearance of
irreversible neurologic syndromes.
A species can be categorized into soluble and insoluble species. Studies show that soluble Aβs, such as
oligomers, are more neurotoxic than insoluble deposits (fibrils and plaques) and serve as biomarkers for pre-
symptomatic stages of AD. In fact, abnormal A levels in brains appear 30 years before symptoms are observed
in humans. Unfortunately, the first-generation (1stG) A PET probes are insensitive and only marginally detect
abnormal A deposits ~ 5 years before clinical AD syndrome diagnosis. This leaves a 25-year gap for which AD
will progress undetectable. The intrinsic limitation of the 1stG PET tracers is their insensitivity to soluble As, the
best biomarker for pre-symptomatic AD. Preliminary results from the PI’s group over the past ten years suggest
that this intrinsic limitation can be overcome with CRANAD-Xs, a series of probes capable of detecting not only
insoluble Aβs but also soluble Aβs in vitro and in vivo. In this application, we propose to adapt our fluorescent
CRANAD-X probes into sensitive Aβ PET tracers to fill the 25-year gap. Expected long-term impact. The
proposed A PET tracers will allow more sensitive detection vs. 1stG PET tracers and consequentially allow
identification of AD patients at an earlier pre-symptomatic stage that is likely more responsive to treatment.

## Key facts

- **NIH application ID:** 10805697
- **Project number:** 1R01AG085562-01
- **Recipient organization:** MASSACHUSETTS GENERAL HOSPITAL
- **Principal Investigator:** Chongzhao Ran
- **Activity code:** R01 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2024
- **Award amount:** $826,732
- **Award type:** 1
- **Project period:** 2023-12-15 → 2028-11-30

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/10805697

## Citation

> US National Institutes of Health, RePORTER application 10805697, Development of sensitive PET tracers of pan-Amyloid-beta species for Alzheimer's disease (1R01AG085562-01). Retrieved via AI Analytics 2026-05-24 from https://api.ai-analytics.org/grant/nih/10805697. Licensed CC0.

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