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首页> 美国卫生研究院文献>MedChemComm >Studies towards elucidating the potential of 5101520-tetrakis(p-carboxy-methyleneoxyphenyl)porphyrin as a theranostic agent for applications in PET and PDT
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Studies towards elucidating the potential of 5101520-tetrakis(p-carboxy-methyleneoxyphenyl)porphyrin as a theranostic agent for applications in PET and PDT

机译：阐明5101520-四（对-羧基-亚甲氧基苯基）卟啉作为兽药的潜力在PET和PDT中的应用研究

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Porphyrins, owing to their inherent tendency to accumulate in tumorous lesions, are considered suitable for developing agents for theranostic applications involving tumor diagnosis and targeted tumor therapy. The aim of the present work is to study the potential of a porphyrin derivative namely, 5,10,15,20-tetrakis(p-carboxymethyleneoxyphenyl)porphyrin (SPTA) as a theranostic agent for applications in positron emission tomography (PET) and photodynamic therapy (PDT). SPTA was synthesized in-house following a three-step reaction process and characterized by using spectroscopic techniques, viz. UV-vis, FT-IR, 1H-NMR and 13C-NMR spectroscopy, as well as by mass spectrometry. SPTA was labeled with 68Ga, a generator produced PET radioisotope, and the radiolabeled product was characterized by HPLC. The 68Ga-SPTA complex was prepared with a radiochemical purity of >95% under optimized conditions. The diagnostic potential of 68Ga-SPTA was evaluated by cell uptake studies in two different tumor cell lines (HT1080 and A549) which revealed the affinity of 68Ga-SPTA towards the cancer cells. Biodistribution studies carried out in Swiss mice bearing fibrosarcoma tumors exhibited the accumulation of the radiotracer in the tumor. The therapeutic potential of SPTA was evaluated by determining its photo-cytotoxicity employing the MTT assay in HT1080 and A549 cell lines using three different light doses, which indicated the significant cytotoxicity of SPTA in the presence of light. The present study indicates the possible potential of SPTA in radionuclide imaging as well as in photodynamic therapy (PDT) thus confirming the promising theranostic nature of this porphyrin derivative.
机译：卟啉由于其固有的在肿瘤性病变中蓄积的趋势，被认为适合用于涉及肿瘤诊断和靶向肿瘤治疗的治疗学应用的显影剂。本工作的目的是研究一种卟啉衍生物，即5,10,15,20-四（对-羧亚甲基氧基苯基）卟啉（SPTA）作为治疗诊断剂的潜力，可用于正电子发射断层扫描（PET）和光动力治疗（PDT）。 SPTA经过三步反应过程在内部合成，并使用分光镜技术进行了表征。紫外可见光谱，傅立叶变换红外光谱， 1 H-NMR和 13 C-NMR光谱以及质谱法。 SPTA用发生器产生的PET放射性同位素 68 Ga标记，并通过HPLC对放射性标记的产物进行表征。在优化条件下制备了 68 Ga-SPTA配合物，其放射化学纯度> 95％。通过在两种不同的肿瘤细胞系（HT1080和A549）中的细胞摄取研究评估了 68 Ga-SPTA的诊断潜力，这揭示了 68 Ga-SPTA对肿瘤的亲和力。癌细胞。在患有纤维肉瘤肿瘤的瑞士小鼠中进行的生物分布研究表明，放射性示踪剂在肿瘤中蓄积。通过使用三种不同光剂量的HT1080和A549细胞系中的MTT分析，通过测定SPTA的光细胞毒性来评估SPTA的治疗潜力，这表明SPTA在光照下具有明显的细胞毒性。本研究表明SPTA在放射性核素成像以及光动力疗法（PDT）中的潜在潜力，从而证实了该卟啉衍生物的有前景的治疗学性质。

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