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随着全球恶性肿瘤发病率的增加,恶性肿瘤的早期诊断和治疗已成为各相关领域的研究焦点,靶向诊断和治疗是以肿瘤的生物学特性为作用靶点,将诊断和治疗药物尽量限制在特定的靶细胞、组织或器官内,达到相对精确诊断和治疗的目的,同时又对正常细胞和组织器官无明显影响,在这个过程中寻找特异性靶点至关重要。整合素αvβ3(integrin αvβ3)作为重要的整合素家族成员,因其在肿瘤新生血管生成中的高度表达而成为研究重点。
以整合素αvβ3为靶点的肿瘤分子显像及靶向治疗
Integrins αvβ3 in molecular imaging and targeted therapy of neoplasms
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摘要: 整合素αvβ3是由两条多肽链组成的跨膜异二聚体糖蛋白,其高表达于肿瘤新生血管内皮细胞和部分肿瘤细胞表面,而在正常血管和组织表面不表达或低表达,其可通过介导细胞黏附来调控肿瘤血管新生,整合素αvβ3能够与体内外含精氨酸-甘氨酸-天冬氨酸序列的物质发生特异性结合。用不同的放射性核素标记,通过PET/CT、SPECT/CT、PET/MRI显像检测肿瘤整合素αvβ3受体的表达水平,在此研究基础上可将其作为肿瘤新生血管显像和肿瘤早期治疗的靶点。现将国内外关于整合素αvβ3靶向药物的设计、放射性核素的选择及相关药物的研究进展等进行综述。
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关键词:
- 新生血管化, 病理性 /
- 整合素αvβ3 /
- 放射性核素显像
Abstract: Integrin αvβ3 are heterodimeric transmembrane glycoproteins, consisting of two noncovalently bound transmembrane subunits. It had a high expression on the tumor but it does not expression on the surface of normal blood vessels or the normal organizations or only had a low level expression. It can regulate tumor angiogenesis by cell adhesion. The integrin αvβ3 can specifically recognize and combine with the peptides which containing tripeptide Arg-Gly-Asp(RGD). These RGD peptides are labeled with appropriate nuclide. The PET/CT, SPECT/CT and PET/MRI multimode imaging can be used to examine the tumor integrin αvβ3 expression level. Thus it can be used as a new target for the tumor angiogenesis imaging and therapy. There is a summary on the design of the integrin αvβ3 agents, the choice of appropriate radionuclides and the research direction of these agents. -
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