Synthesis, radiolabeling, and evaluation of 68Ga-labeled aminoquinoxaline derivative as a potent PFKFB3-targeted PET tracer

Frontiers in Chemistry

Chemistry

Feijing Su¹  Rui Huang²  Xiaoai Wu³  Honghai Yin³  Yixuan Ma⁴  Yi Wu⁴  Feng Chen⁵  Qian Liu⁶ 

[1]Core Facilities of West China Hospital, Sichuan University, Sichuan, China

[2]Department of Neurology, Sichuan Academy of Medical Science and Sichuan Provincial People’s Hospital, Chengdu, China

[3]Department of Nuclear Medicine, Laboratory of Clinical Nuclear Medicine, National Clinical Research Center for Geriatrics, West China Hospital, Sichuan University, Chengdu, China

[4]Key Laboratory of Prevention and Treatment of Cardiovascular and Cerebrovascular Diseases, Ministry of Education, Gannan Medical University, Ganzhou, China

[5]Suzhou Medical College of Soochow University, Suzhou, Jiangsu, China

[6]Department of Pediatric Surgery, The First Affiliated Hospital of Gannan Medical University, Ganzhou, Jiangxi, China

[7]Key Laboratory of Prevention and Treatment of Cardiovascular and Cerebrovascular Diseases, Ministry of Education, Gannan Medical University, Ganzhou, China

[8]Jiangxi Provincial Clinical Research Center for Vascular Anomalies, The First Affiliated Hospital of Gannan Medical University, Ganzhou, Jiangxi, China

[9]Suzhou Medical College of Soochow University, Suzhou, Jiangsu, China

[10]Jiangxi Provincial Clinical Research Center for Vascular Anomalies, The First Affiliated Hospital of Gannan Medical University, Ganzhou, Jiangxi, China

[11]Integrated Chinese and Western Medicine Institute for Children Health & Drug Innovation, Jiangxi University of Chinese Medicine, Nanchang, Jiangxi, China

[12]Jiangxi Key Laboratory of TCM for Prevention and Treatment on Hemangioma, Nanchang, Jiangxi, China

关键词: PFKFB3;    radiolabeled compounds;    inhibitors;    PET tracers;    PET;   

DOI  :  10.3389/fchem.2023.1158503

 received in 2023-02-04, accepted in 2023-03-09,  发布年份 2023

来源: Frontiers

【 摘 要 】

Glycolysis, as a multi-step oxidation process, plays important roles in the energy supply for living cells, including malignant tumor cells. Recent studies have revealed that 6-phosphofructo-2-kinase/fructose-2,6-biphosphatase 3 (named PFKFB3), a bifunctional enzyme in glycolysis, is upregulated in a variety of malignant solid tumors and has been regarded as a potential biomarker for the diagnosis and treatment of tumor patients. Based on the structure of selective PFKFB3 inhibitors, we designed and synthesized a radio-metal radiolabeled small molecule, 68Ga-5, which also showed potent selectivity in enzymatic and biochemical tests (with an IC50 value of 12.5 nM). According to further in vitro and in vivo evaluations, 68Ga-5 showed promising properties as a PET ligand, and selective accumulation in PFKFB3-positive tumors was observed in PET images (with max SUV values of 0.60). Our results indicated that radio-metal radiolabeled aminoquinoxaline derivative, as represented by 68Ga-5, held the potential to be developed as selective PFKFB3-targeted PET tracers, and further investigation and optimization would also be required for this scaffold.

【 授权许可】

Unknown   
Copyright © 2023 Chen, Wu, Ma, Yin, Su, Huang, Wu and Liu.