# Metal-Mediated C-H Radiofluorination for Rapid Access to PET Imaging Agents

> **NIH NIH R00** · UNIVERSITY OF PENNSYLVANIA · 2024 · $249,000

## Abstract

Project Summary/Abstract 
Fluorine is an essential constituent of many commercial molecules, including (radio)pharmaceuticals, 
agrochemicals, and functional materials. Fluorine-19 ( stable isotope) is routinely introduced into 
pharmaceuticals to modulate pharmacological properties. Many positron emission tomography (PET) 
imaging agents are labeled with fluorine-18 (radioactive isotope) for studying and monitoring disease, 
evaluating drug-target engagements, and enriching clinical trials of therapeutics. Critically, PET is continually 
used to improve disease detection, treatment, and prevention, which is fundamentally consistent with the 
mission of NIBIB. Despite progress in developing fluorine-18 imaging agents for these applications, more 
robust, efficient, and reproducible radiosyntheses are required to support and expedite tracer discovery and 
meet the urgent demand for radiopharmaceuticals from the healthcare and pharmaceutical industries. 
Therefore, the primary focus of this proposal is to overcome challenges associated with radiofluorination by 
inventing radiolabeling methods that support the design of PET imaging agents. Specifically, the central claim 
is that fluorine-18 labeled organic molecules can be rapidly accessed by designing zinc-mediated and metal-free amide C-H radiofluorination radiolabeling reactions. Zinc is an abundant, inexpensive, and non-toxic 
element that facilitates a-amido C-H radiofluorination reactions, albeit inefficiently, with a limited scope. Over 
the K99 phase, the candidate collected rigorous preliminary data demonstrating that amide C-H 
radiofluorination reactions are possible, and this award will study, refine, optimize, and showcase this protocol 
for PET biomedical imaging applications. Specifically, the ROO proposal is divided into three aims: Aim 1 is 
to develop a fully optimized amide C-H radiofluorination protocol that delivers stereochemically enriched 
fluorine-18 labeled amides containing a broad range of valuable fluoroalkyl functional groups. Aim 2 is to 
demonstrate the feasibility of new amide C-H radiofluorination reactions with bioactive PET imaging scaffolds 
on a commercial radiosynthesis module for clinical production Aim 3 is to prepare and assess the stability of 
multiple representative therapeutics containing fluorine-18 labeled amides. Ultimately, the enhancement of 
PET imaging technology, as described in this proposal, is expected to fundamentally alter the current 
(radio)synthetic fluorination paradigm and expedite radiofluorination, providing unrealized and rapid access 
to fluorine-18 labeled pharmaceuticals that support the improvement of patient outcomes and a reduction in 
healthcare costs for the American people in the long term. Broadly, this project will provide new opportunities 
to merge radiochemistry and organic/organometallic chemistry, supporting the development of a world-leading radiosynthetic methods program at the University of Pennsylvania.

## Key facts

- **NIH application ID:** 11142019
- **Project number:** 4R00EB031564-03
- **Recipient organization:** UNIVERSITY OF PENNSYLVANIA
- **Principal Investigator:** Jay Samuel Wright
- **Activity code:** R00 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2024
- **Award amount:** $249,000
- **Award type:** 4N
- **Project period:** 2024-09-01 → 2027-08-31

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/11142019

## Citation

> US National Institutes of Health, RePORTER application 11142019, Metal-Mediated C-H Radiofluorination for Rapid Access to PET Imaging Agents (4R00EB031564-03). Retrieved via AI Analytics 2026-05-24 from https://api.ai-analytics.org/grant/nih/11142019. Licensed CC0.

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