One-step Radiosynthesis and Preclinical Evaluation of Molecular Tracer [¹⁸F]FEtO-CHC Targeting Monocarboxylate Transporters for PET Imaging in Tumor-bearing Mice.

IF 3 4区医学 Q2 RADIOLOGY, NUCLEAR MEDICINE & MEDICAL IMAGING

Molecular Imaging and Biology Pub Date : 2025-06-11 DOI:10.1007/s11307-025-02024-1

Dongmei Shi, Ling Liu, Di Zhang, Yuzhou Zheng, Wenhao Hu, Ping Wu, Xinzhong Hao, Haiyan Liu, Jie Gao, Jianguo Li, Zhifang Wu, Sijin Li, Hongliang Wang

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引用次数: 0

Abstract

Purpose: Monocarboxylate transporters (MCTs) play a pivotal role in tumor metabolic symbiosis, acid resistance, and metastatic progression. Herein, we report the development of [¹⁸F]FEtO-CHC, a novel MCTs-targeted positron emission tomography (PET) radiotracer, and systematically evaluate its potential for non-invasive tumor imaging.

Procedures: The radiosynthesis of [¹⁸F]FEtO-CHC and its non-radioactive analog was achieved through optimized precursor synthesis and fluorination protocols. Comprehensive in vitro characterization encompassed: radiochemical purity and stability assessments, cellular uptake kinetics and inhibition assays in MCT-expressing BxPC3 (pancreatic) and 4T1 (breast) cancer models, biodistribution and dynamic micro-PET/CT imaging in tumor-bearing murine models.

Results: [¹⁸F]FEtO-CHC, a CHC-derived radioligand, was synthesized via streamlined one-step radiosynthesis with 52.08 ± 6.74% decay-corrected yield (n=7), >99% radiochemical purity, and excellent stability. Cellular studies demonstrated MCTs-dependent uptake with significant suppression (>70%) by α-CHC competition. In vivo pharmacokinetics revealed favorable metabolic stability with dual hepatorenal clearance. Tumor uptake correlated with MCT expression levels, as confirmed by immunohistochemistry.

Conclusions: This study establishes an efficient one-step radiosynthetic approach for [¹⁸F]FEtO-CHC production and validates its specificity as a MCT-targeted PET probe, offering potential utility in tumor imaging with further structural optimization.

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靶向单羧酸转运体的FEtO-CHC分子示踪剂[18F]在载瘤小鼠PET成像中的一步放射合成及临床前评价。

目的：单羧酸转运蛋白（mct）在肿瘤代谢共生、耐酸和转移进展中起关键作用。在此，我们报道了[18F]FEtO-CHC的发展，这是一种新型的mcts靶向正电子发射断层扫描（PET）放射性示踪剂，并系统地评估了其在非侵入性肿瘤成像中的潜力。方法：通过优化前体合成和氟化方案，实现[18F]FEtO-CHC及其非放射性类似物的放射性合成。全面的体外表征包括：放射化学纯度和稳定性评估，表达mct的BxPC3（胰腺）和4T1（乳腺癌）模型的细胞摄取动力学和抑制试验，荷瘤小鼠模型的生物分布和动态微pet /CT成像。结果：[18F]FEtO-CHC是一种chc衍生的放射性配体，采用流线型一步放射合成方法合成，衰变校正产率（n=7）为52.08±6.74%，放射化学纯度为bb0 99%，稳定性良好。细胞研究显示mcts依赖性摄取被α-CHC竞争显著抑制（bbb70 %）。体内药代动力学显示具有良好的代谢稳定性和双肝肾清除。免疫组织化学证实，肿瘤摄取与MCT表达水平相关。结论：本研究建立了一种高效的一步合成[18F]FEtO-CHC的方法，并验证了其作为mct靶向PET探针的特异性，通过进一步的结构优化，在肿瘤成像中具有潜在的应用价值。

本文章由计算机程序翻译，如有差异，请以英文原文为准。

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来源期刊

Molecular Imaging and Biology 医学-核医学

CiteScore

6.90

自引率

3.20%

发文量

审稿时长

3 months

期刊介绍： Molecular Imaging and Biology (MIB) invites original contributions (research articles, review articles, commentaries, etc.) on the utilization of molecular imaging (i.e., nuclear imaging, optical imaging, autoradiography and pathology, MRI, MPI, ultrasound imaging, radiomics/genomics etc.) to investigate questions related to biology and health. The objective of MIB is to provide a forum to the discovery of molecular mechanisms of disease through the use of imaging techniques. We aim to investigate the biological nature of disease in patients and establish new molecular imaging diagnostic and therapy procedures. Some areas that are covered are: Preclinical and clinical imaging of macromolecular targets (e.g., genes, receptors, enzymes) involved in significant biological processes. The design, characterization, and study of new molecular imaging probes and contrast agents for the functional interrogation of macromolecular targets. Development and evaluation of imaging systems including instrumentation, image reconstruction algorithms, image analysis, and display. Development of molecular assay approaches leading to quantification of the biological information obtained in molecular imaging. Study of in vivo animal models of disease for the development of new molecular diagnostics and therapeutics. Extension of in vitro and in vivo discoveries using disease models, into well designed clinical research investigations. Clinical molecular imaging involving clinical investigations, clinical trials and medical management or cost-effectiveness studies.