# Diversifying Radiochemistry Toward Practical Approaches for the Synthesis and Application of Imaging Agents

> **NIH NIH F31** · UNIVERSITY OF TEXAS DALLAS · 2021 · $46,036

## Abstract

Positron Emission Tomography (PET) is a high precision imaging tool for early disease diagnosis and treatment
efficacy monitoring. A continuous demand for new imaging agents and the absence of practical, robust, selective
methods for their synthesis calls for expanding the existing radiochemistry technologies. In Specific Aim I we
propose a new prosthetic group approach toward 18F incorporation. Fluorine-18 is preferred for its favorable
positron emission properties and longer half-life (t1/2 = 110 min), so imaging agents can be produced remotely
and distributed to hospitals. A traditional radiofluorination of complex molecules by late-stage functional group
interconversion is limited by challenging synthesis of each precursor. The alternative approaches relying on
direct C–H activation methodologies are at their nascent stages. They exhibit low radiochemichal yields (RCY)
and innate substrate control of the fluorination sites, which can be restrictive to target binding. Low selectivity,
common to this approach, might result in inseparable isomer mixtures, thus preventing the clinical use of these
PET imaging probes due to FDA regulations. The prosthetic group approach, despite requiring one extra step,
offers perfect fluorine site-selectivity. Our proposed prosthetic method features robust fluorination at easily
accessible terminal olefins followed by rapid C–C bond formation toward the synthesis of diverse radiofluorinated
compounds. If successful, it would allow unprecedented access to the use of aromatic, heteroaromatic, and
aliphatic groups bearing desirable functionalities for PET imaging. In Specific Aim II we propose the application
of visible light-induced palladium chemistry toward rapid hybrid 11C-methyl radical addition to produce
radiomethylated imaging agents. Carbon-11 has a much shorter half-life than fluorine-18 (t1/2 = 20 min), so
radiotracer synthesis is extremely challenging. The current methods for 11C-incorporation rely on methylation,
with nucleophilic substitution of heteroatoms as the most common strategy. Coupling reactions are much less
developed though stoichiometric approaches have been reported. It is expected that our hybrid radical approach
could improve methods for rapid methylation toward 11C-labeled PET imaging agents. In Specific Aim III we will
apply the proposed methods under development toward the synthesis of a library of agents to target HIF2α and
tau prions. The most important applications of PET imaging concern early diagnosis and treatment progression
monitoring of cancer and neurodegenerative diseases. Based on the structural features of published inhibitors
and radioligands, we selected two potential applications of our proposed methods: HIF2α, a transcription factor
selectively found in certain malignancies, whose expression is a negative prognosis; and tau protein, a hallmark
of neurodegenerative diseases, such as Alzheimer’s Disease. The “cold” chemistry will be carried out at The
University of Tex...

## Key facts

- **NIH application ID:** 10216180
- **Project number:** 5F31GM139395-02
- **Recipient organization:** UNIVERSITY OF TEXAS DALLAS
- **Principal Investigator:** Mónica Rivas
- **Activity code:** F31 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2021
- **Award amount:** $46,036
- **Award type:** 5
- **Project period:** 2020-08-01 → 2022-07-31

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/10216180

## Citation

> US National Institutes of Health, RePORTER application 10216180, Diversifying Radiochemistry Toward Practical Approaches for the Synthesis and Application of Imaging Agents (5F31GM139395-02). Retrieved via AI Analytics 2026-05-24 from https://api.ai-analytics.org/grant/nih/10216180. Licensed CC0.

---

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