# Novel Catalytic Methods for Efficient Radiolabeling of Un-activated Arene Compounds Supplement

> **NIH NIH R01** · UNIV OF NORTH CAROLINA CHAPEL HILL · 2021 · $386,477

## Abstract

Abstract
 Positron emission tomography (PET) is a powerful and rapidly developing technology that plays key roles
in medical imaging, including the research of Alzheimer’s disease. Despite the exceptional promise of PET
imaging, the availability of PET agents is limited in many situations due to the lack of efficient and simple labeling
methods to modify biologically active small molecules/drugs. Based on the highly innovative photoredox systems
described by the Nicewicz group, Li, Wu and Nicewicz have made the first breakthrough on direct arene C–H
fluorination with 18F- that allows direct conversion of drugs to PET agents; followed by SNAr radiofluorination that
could precisely control the radiofluorination position on aromatic substrates. This new method indeed provide us
access to agents that are previously challenging or impossible to synthesize. Based on the Nucleophilic Aromatic
Substitution we just developed, initial success was made on the synthesis of innovative PET agents for synapse
density imaging. Affecting 6 million people in the USA, Alzheimer’s disease (AD) is increasingly viewed as a
malignancy that progressed from preclinical AD, to mild cognitive impairment (MCI), and to AD. Because
synapses are crucial for cognitive function, synaptic loss has been observed as a promising prognosis marker
in AD patients. The ability to monitor synaptic density in vivo would therefore be important in AD patient
management. Based on the critical need of synapse density imaging and our initial success, we will validate the
new agents in normal and AD animals in this supplement. The success of this approach could not only lead to
new PET agents for AD patients, but also increase the availability of the PET agent due to simpler and milder
reaction conditions. Two aims are proposed here. In Aim 1, we will establish the radiochemistry of 18F-UCB
agents for synapse density imaging. In order to make the agent widely available to the field with low cost, we will
also develop LED light based synthetic method for our UCB agents. In Aim 2, we will characterize the sensitivity
of our 18F-UCB agent in normal and AD mice. In summary, photoredox reactions are entirely new methods for
the incorporation of [18F]F into aromatic compounds. The mild conditions coupled with easy access to the
required precursors will allow for the unprecedented access to novel aromatic [18F] PET tracers for use in
neurology. The goal of this supplement is to develop and validate innovative PET agents to image synaptic loss
in AD model based on our newly developed labeling method.

## Key facts

- **NIH application ID:** 10288052
- **Project number:** 3R01EB029451-02S1
- **Recipient organization:** UNIV OF NORTH CAROLINA CHAPEL HILL
- **Principal Investigator:** Zibo Li
- **Activity code:** R01 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2021
- **Award amount:** $386,477
- **Award type:** 3
- **Project period:** 2020-05-01 → 2024-01-31

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/10288052

## Citation

> US National Institutes of Health, RePORTER application 10288052, Novel Catalytic Methods for Efficient Radiolabeling of Un-activated Arene Compounds Supplement (3R01EB029451-02S1). Retrieved via AI Analytics 2026-05-25 from https://api.ai-analytics.org/grant/nih/10288052. Licensed CC0.

---

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