# [18F]Fluoronicotinic-Acid-Conjugated Folate as a Novel Candidate Positron Emission Tomography Tracer for Inflammation

## TL;DR

This paper introduces a new PET imaging agent, [18F]FNA–folate, that can detect folate receptor expression in inflammatory diseases.

## Contribution

The novel [18F]FNA–folate tracer shows potential for imaging folate receptors in inflammation with high specificity and stability.

## Key findings

- The radiotracer demonstrated excellent in vitro and in vivo stability and rapid blood clearance in animal models.
- It showed focal and intense uptake in heart tissue from a rat model of myocardial infarction, indicating macrophage folate receptor binding.
- The radiosynthesis process is straightforward, supporting further development for clinical use in inflammatory diseases.

## Abstract

Folate receptors are clinically relevant targets, as
evidenced
by therapeutic agents, including mirvetuximab soravtansine-gynx, an
antibody–drug conjugate recently approved for cancer treatment.
In this study, we report the development of a novel positron emission
tomography (PET) imaging agent, [18F]­fluoronicotinic-acid-conjugated
folate ([18F]­FNA–folate), for the evaluation of
folate receptor expression. The [18F]­FNA–folate
was synthesized via the N-acylation of an amino-functionalized folate
derivative with [18F]­FNA 4-nitrophenyl ester under mild
reaction conditions. The resulting radiotracer exhibited excellent in vitro and in vivo stability, rapid blood
clearance, and minimal bone uptake in mice and rats. In vitro tissue binding studies using heart sections from an experimental
rat model of myocardial infarction demonstrated focal, intense, and
heterogeneous uptake of [18F]­FNA–folate, and the
binding specificity to macrophage folate receptors was confirmed.
The straightforward radiosynthesis, excellent in vivo stability, and target-specific binding support further development
of [18F]­FNA–folate as a promising PET imaging agent
for inflammatory diseases.