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

A1 Refereed original research article in a scientific journal

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

Authors: Zhuang, Xiaoqing; Kunnas, Jonne; Ekwe, David; Bakay, Emel; Dillemuth, Pyry; Liljenbäck, Heidi; Iqbal, Imran; Rajander, Johan; Low, Philip S.; Knuuti, Juhani; Rosenholm, Jessica M.; Saraste, Antti; Roivainen, Anne; Li, Xiang-Guo

Publisher: American Chemical Society (ACS)

Publication year: 2025

Journal: ACS Omega

Article number: acsomega.5c10157

ISSN: 2470-1343

eISSN: 2470-1343

DOI: https://doi.org/10.1021/acsomega.5c10157

Publication's open availability at the time of reporting: Open Access

Publication channel's open availability : Open Access publication channel

Web address : https://doi.org/10.1021/acsomega.5c10157

Self-archived copy’s web address: https://research.utu.fi/converis/portal/detail/Publication/506381648

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.

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Funding information in the publication:
This work was supported by research grants from the State Research Funding of Turku University Hospital (11009), the Turku University Foundation, the Finnish Cultural Foundation, the Sigrid Jusélius Foundation, the Finnish Cancer Foundation, the Tampere Tuberculosis Foundation, the Finnish Foundation for Cardiovascular Research, and the Research Council of Finland (Funding Decisions 368560 and 350117). This research was also partially supported by the InFLAMES Research Flagship (Funding Decisions 337531, 337530, 359346, and 357910), which is funded under the Research Council of Finland’s Finnish Flagship Program.