放射性核素标记耐久霉素细胞凋亡显像的研究进展

Development of Radiolabeled Duramycin for Apoptosis Imaging

  • 摘要: 细胞凋亡是细胞死亡的一种重要形式,广泛存在于多种生理和病理过程中。细胞凋亡早期,胞膜内的磷脂酰乙醇胺(Phosphatidylethanolamine,PE)会翻转到细胞膜外表面,这一特征可以作为凋亡显像的靶点。耐久霉素(Duramycin)可与PE特异性结合,以放射性核素对耐久霉素进行标记后,可以利用核医学分子影像的手段,实现对细胞凋亡的活体无创检测。活体凋亡显像能在细胞水平上对肿瘤组织的改变进行早期、无创、动态的监测,从而准确判断肿瘤细胞对治疗药物的反应,有助于为临床个体化治疗方案的制定提供指导性意见。本文对放射性标记耐久霉素用于细胞凋亡显像的原理进行了总结和阐述,就近年来在凋亡显像示踪剂种类、制备及纯化方法、生物分布特征及其在肿瘤治疗早期疗效评估等方面的研究进展进行了综述,并对放射性核素标记耐久霉素的临床应用前景进行了展望。

     

    Abstract: Cell apoptosis, or programmed cell death, is an important form of cell death, which extensively exists in the physiological and pathological processes of the formation and progression of many diseases. The ubiquitous presence of externalized phosphatidylethanolamine (PE) on apoptosis cells makes it an attractive target for in vivo molecular imaging of apoptosis. Apoptosis imaging provides a noninvasive and dynamic approach to monitor the therapy induced cellular changes in tumor, thus it is valuable in the evaluation of early tumor response to anticancer therapy, and may serve as a helpful tool for individualized treatment in clinical practice. Duramycin is a peptide that binds to PE with high affinity in the nanomolar range. Preclinical studies had shown the potential of radiolabeled duramycin for imaging of cell apoptosis associated with PE exposure. In this review, principles of apoptosis detection, preparation, purification and biodistribution characteristics of radiolabeled duramycin were summarized. Preclinical applications of 99mTc-HYNIC-Duramycin for the non-invasive imaging of cell apoptosis in response evaluation of tumors at early stage were specifically emphasized.

     

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