膜联蛋白在肿瘤凋亡显像中的研究进展

目前的影像学检查方法尚不能在肿瘤治疗早期即对疗效进行有效判断,而活体凋亡显像能在细胞水平对肿瘤组织的改变进行早期、无创、动态监测,从而准确判断肿瘤细胞对化疗药物的反应。磷脂酰丝氨酸(PS)由细胞膜内侧翻转到细胞膜表面是细胞凋亡早期最具特征性的改变之一,这使得PS成为细胞凋亡显像的有效靶点。放射性核素标记的膜联蛋白可选择性与翻转到细胞膜表面的PS结合,从而可在体内对早期疗效进行判断。由于在有效的抗肿瘤治疗开始24 h后即可观察到大量的肿瘤细胞发生凋亡,因此活体凋亡显像有助于为临床个体化治疗方案的制订提供指导性意见。本文在临床前研究和临床试验两方面对膜联蛋白凋亡显像在抗肿瘤治疗早期疗效评价中的机制、应用、局限性及未来发展前景作一综述。

Advance in apoptosis imaging with annexins in tumor research

Current imaging methods can provide little helpful information about the tumor response to effective treatments in a very early stage.However,apoptosis imaging offers an early,noninvasive and dynamic way to monitor the therapy-induced cellular changes,and contributes to knowing the early response in vivo.One of the most prominent characteristics ot apoptosis is the externalization of phosphatidylserine（PS）,which resides predominantly in the inner leaflet of the plasma membrane in healthy cells.This feature has made PS a well target to image apoptosis.Radio labeled annexins have shown the ability to selectively combine with PS undergoing apoptosis in response to successful treatment in vivo.As abundant of apoptotic cancer cells can be shown 24 h after effective therapy,apoptosis imaging can help to provide instruction for individualized treatment in clinic.In this review we will provide an overview about the mechanism,applications,limitations,and future perspectives of the apoptosis imaging with annexins in tumor response to successful treatment in both preclinical experiments and clinical trials.