d'Orchymont Faustine, Holland Jason P
University of Zurich, Department of Chemistry, Winterthurerstrasse 190, CH-8057, Zurich, Switzerland.
Commun Chem. 2023 Jun 1;6(1):107. doi: 10.1038/s42004-023-00906-5.
Dual-modality imaging agents featuring both a radioactive complex for positron emission tomography (PET) and a fluorophore for optical fluorescence imaging (OFI) are crucial tools for reinforcing clinical diagnosis and intraoperative surgeries. We report the synthesis and characterisation of bimodal mechanically interlocked rotaxane-based imaging agents, constructed via the cucurbit[6]uril CB[6]-mediated alkyne-azide 'click' reaction. Two synthetic routes involving four- or six-component reactions are developed to access asymmetric rotaxanes. Furthermore, by using this rapid and versatile approach, a peptide-based rotaxane targeted toward the clinical prostate cancer biomarker, prostate-specific membrane antigen (PSMA), and bearing a Ga-radiometal ion complex for positron emission tomography and fluorescein as an optically active imaging agent, was synthesised. The chemical and radiochemical stability, and the cellular uptake profile of the radiolabelled and fluorescent rotaxane was evaluated in vitro where the experimental data demonstrate the viability of using an asymmetric rotaxane platform to produce dual-modality imaging agents that specifically target prostate cancer cells.
兼具用于正电子发射断层扫描（PET）的放射性复合物和用于光学荧光成像（OFI）的荧光团的双模态成像剂，是加强临床诊断和术中手术的关键工具。我们报告了通过葫芦[6]脲CB[6]介导的炔烃-叠氮化物“点击”反应构建的基于双模态机械互锁轮烷的成像剂的合成与表征。开发了两条涉及四组分或六组分反应的合成路线来制备不对称轮烷。此外，通过使用这种快速且通用的方法，合成了一种基于肽的轮烷，该轮烷靶向临床前列腺癌生物标志物前列腺特异性膜抗原（PSMA），并带有用于正电子发射断层扫描的镓放射性金属离子复合物和作为光学活性成像剂的荧光素。在体外评估了放射性标记和荧光轮烷的化学和放射化学稳定性以及细胞摄取情况，实验数据证明了使用不对称轮烷平台生产特异性靶向前列腺癌细胞的双模态成像剂的可行性。
