Legumain-Triggered Macrocyclization of Radiofluorinated Tracer for Enhanced PET Imaging,Bioconjugate Chemistry

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Legumain-Triggered Macrocyclization of Radiofluorinated Tracer for Enhanced PET Imaging
Bioconjugate Chemistry ( IF 4.0 ) Pub Date : 2024-04-10 , DOI: 10.1021/acs.bioconjchem.4c00128
Xiaoqing Gao _{1,

2} , Qianhui Wang _{1,

2} , Xiaofeng Yang _{1,

2} , Jing Fang ₂ , Huirong Li ₂ , Hongjie Xi ₂ , Jianguo Lin ₂ , Ling Qiu _{1,

2}

Affiliation

Enhancing the accumulation and retention of small-molecule probes in tumors is an important way to achieve accurate cancer diagnosis and therapy. Enzyme-stimulated macrocyclization of small molecules possesses great potential for enhanced positron emission tomography (PET) imaging of tumors. Herein, we reported an ¹⁸F-labeled radiotracer [¹⁸F]AlF-RSM for legumain detection in vivo. The tracer was prepared by a one-step aluminum-fluoride-restrained complexing agent ([¹⁸F]AlF-RESCA) method with high radiochemical yield (RCY) (88.35 ± 3.93%) and radiochemical purity (RCP) (>95%). More notably, the tracer can be transformed into a hydrophobic macrocyclic molecule under the joint action of legumain and reductant. Simultaneously, the tracer could target legumain-positive tumors and enhance accumulation and retention in tumors, resulting in the amplification of PET imaging signals. The enhancement of radioactivity enables PET imaging of legumain activity with high specificity. We envision that, by combining this highly efficient ¹⁸F-labeled strategy with our intramolecular macrocyclization reaction, a range of radiofluorinated tracers can be designed for tumor PET imaging and early cancer diagnosis in the future.

中文翻译：

Legumain 触发的放射性氟化示踪剂大环化，用于增强 PET 成像

增强小分子探针在肿瘤中的积累和保留是实现准确癌症诊断和治疗的重要途径。酶刺激的小分子大环化在增强肿瘤的正电子发射断层扫描（PET）成像方面具有巨大潜力。在此，我们报道了一种 ¹⁸F 标记的放射性示踪剂 [¹⁸F]AlF-RSM，用于体内豆类检测。采用一步法氟化铝抑制络合剂（[¹⁸F]AlF-RESCA）法制备示踪剂，放射化学产率（RCY）（88.35 ± 3.93%）和放射化学纯度（RCP）（>95%）。更值得注意的是，示踪剂可以在豆类和还原剂的共同作用下转化为疏水性大环分子。同时，示踪剂可以靶向豆科生物阳性肿瘤并增强肿瘤中的积累和保留，从而放大 PET 成像信号。放射性的增强使豆类活性的 PET 成像具有高度特异性。我们设想，通过将这种高效的 ¹⁸F 标记策略与我们的分子内大环化反应相结合，可以设计一系列放射性氟化示踪剂，用于未来的肿瘤 PET 成像和早期癌症诊断。

更新日期：2024-04-10

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