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

Abstract

<p>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 <em>in vitro</em> and <em>in vivo</em> stability, rapid blood clearance, and minimal bone uptake in mice and rats. <em>In vitro</em> 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 <em>in vivo</em> stability, and target-specific binding support further development of [¹⁸F]FNA–folate as a promising PET imaging agent for inflammatory diseases.<br></p>