Development of a novel radiofluorinated riboflavin probe for riboflavin receptor-targeting PET imaging

Jindian Li; Juno Van Valkenburgh; Jianyang Fang; Deliang Zhang; Yingxi Chen; Quan Chen; Guorong Jia; Austin Z. Chen; Xianzhong Zhang; Kai Chen

Pharmacological Research (Sep 2022)

Development of a novel radiofluorinated riboflavin probe for riboflavin receptor-targeting PET imaging

Jindian Li,
Juno Van Valkenburgh,
Jianyang Fang,
Deliang Zhang,
Yingxi Chen,
Quan Chen,
Guorong Jia,
Austin Z. Chen,
Xianzhong Zhang,
Kai Chen

Affiliations

Jindian Li: Department of Radiology, Keck School of Medicine, University of Southern California, 2250 Alcazar Street, CSC-135D, Los Angeles, CA 90033, USA; Center for Molecular Imaging and Translational Medicine, School of Public Health, Xiamen University, Xiamen 361102, China
Juno Van Valkenburgh: Department of Radiology, Keck School of Medicine, University of Southern California, 2250 Alcazar Street, CSC-135D, Los Angeles, CA 90033, USA
Jianyang Fang: Center for Molecular Imaging and Translational Medicine, School of Public Health, Xiamen University, Xiamen 361102, China
Deliang Zhang: Center for Molecular Imaging and Translational Medicine, School of Public Health, Xiamen University, Xiamen 361102, China
Yingxi Chen: Center for Molecular Imaging and Translational Medicine, School of Public Health, Xiamen University, Xiamen 361102, China
Quan Chen: Department of Radiology, Keck School of Medicine, University of Southern California, 2250 Alcazar Street, CSC-135D, Los Angeles, CA 90033, USA
Guorong Jia: Department of Radiology, Keck School of Medicine, University of Southern California, 2250 Alcazar Street, CSC-135D, Los Angeles, CA 90033, USA
Austin Z. Chen: Department of Radiology, Keck School of Medicine, University of Southern California, 2250 Alcazar Street, CSC-135D, Los Angeles, CA 90033, USA
Xianzhong Zhang: Center for Molecular Imaging and Translational Medicine, School of Public Health, Xiamen University, Xiamen 361102, China; Corresponding authors.
Kai Chen: Department of Radiology, Keck School of Medicine, University of Southern California, 2250 Alcazar Street, CSC-135D, Los Angeles, CA 90033, USA; Corresponding authors.

Journal volume & issue: Vol. 183
p. 106395

Abstract

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Riboflavin receptor 3 (RFVT3) is a key protein in energetic metabolism reprogramming and is overexpressed in multiple cancers involved in malignant proliferation, angiogenesis, chemotherapy resistance, and immunosuppression. To enable non-invasive real-time quantification of RFVT3 in tumors, we sought to develop a suitable PET probe that would allow specific and selective RFVT3 imaging in vivo. A novel radiofluorinated riboflavin probe (18F-RFTA) based on riboflavin was synthesized and characterized in terms of radiochemical purity, hydrophilicity, binding affinity, and stability. Positron emission tomography (PET) imaging of 18F-RFTA was performed in U87MG tumor-bearing mice. Immunohistochemistry staining was carried out to determine the expression of RFVT3 in U87MG tumors. 18F-RFTA was characterized by high radiochemical purity and RFVT3 binding affinity, and remarkable stability in vitro and in vivo. Small-animal PET imaging with 18F-RFTA revealed significantly higher uptake in RFVT3-expressing U87MG tumors than in muscle. In conclusion, we have developed the first radiofluorinated riboflavin-based PET probe that is suitable for imaging RFVT3-positive tumors. The new target/probe system can be leveraged for extensive use in the diagnosis and treatment of RFVT3 overexpressing diseases, such as oncologic, cardiovascular, and neurodegenerative diseases.

Published in Pharmacological Research

ISSN: 1096-1186 (Online)
Publisher: Elsevier
Country of publisher: United Kingdom
LCC subjects: Medicine: Therapeutics. Pharmacology
Website: https://www.sciencedirect.com/journal/pharmacological-research

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