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Integrin alpha(v)beta(3) and RGD-based radiopharmaceuticals

机译：整联蛋白alpha（v）beta（3）和基于RGD的放射性药物

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摘要

Positron emission tomography combined with computed tomography (PET/CT) using RGD-based radiopharmaceuticals allows quantification of tumour expression of integrin alpha(v)beta(3) in vivo. Integrins and, in particular, integrin alpha(v)beta(3) are involved in numerous physiologic and pathologic processes, including angiogenesis. RGD-based radiopharmaceuticals targeting integrin 043, expressed by activated endothelial cells, have been developed in order to quantify angiogenesis. However, integrin a 133 is also frequently expressed by tumour cells and/or tumour microenvironment cells, e.g., bone marrow derived cells and osteoclasts in bone. Upregulation of integrin alpha(v)beta(3) by tumour cells promotes cell survival, proliferation, invasion, metastasis and resistance to treatment. Therefore, the PET signal related to RGD-based radiopharmaceuticals may not reflect angiogenesis only. Moreover, tumours may develop mechanisms other than angiogenesis to ensure blood supply such as vascular mimicry, vessel co-option and intussusceptive angiogenesis that might not be assessed with RGD PET/CT. In the setting of treatment assessment, a drop of the RGD PET signal certainly means tumour response (endothelial and/or tumour cell apoptosis and/or vessel normalisation). On the other hand, a stable or increased RGD PET signal may be related to absence of response or upregulation of integrin alpha(v)beta(3) in adaptative response to therapy, promoting resistance. This review illustrates the complexity of the role of integrin alpha(v)beta(3) in oncology and its role in non-oncologic diseases such as osteoarthtitis and cardiovascular diseases. (C) 2015 Elsevier Masson SAS. All rights reserved.
机译：正电子发射断层扫描与计算机断层扫描（PET / CT）结合使用基于RGD的放射性药物，可以定量体内整合素α（v）beta（3）的肿瘤表达。整联蛋白，尤其是整联蛋白α（v）beta（3）参与许多生理和病理过程，包括血管生成。为了定量血管生成，已经开发出了以RGD为基础的放射性药物，该药物靶向由活化的内皮细胞表达的整联蛋白043。然而，整联蛋白a 133也经常由肿瘤细胞和/或肿瘤微环境细胞例如骨髓来源的细胞和骨中的破骨细胞表达。肿瘤细胞对整联蛋白α（v）β（3）的上调促进细胞存活，增殖，侵袭，转移和对治疗的抵抗力。因此，与基于RGD的放射性药物相关的PET信号可能不仅仅反映血管生成。此外，肿瘤可能会发展除血管生成以外的其他机制来确保血液供应，例如可能无法通过RGD PET / CT评估的血管模仿，血管共存选择和肠套叠血管生成。在治疗评估的背景下，RGD PET信号下降肯定意味着肿瘤反应（内皮和/或肿瘤细胞凋亡和/或血管正常化）。另一方面，RGD PET信号的稳定或增加可能与对治疗的适应性反应中无应答或整联蛋白alpha（v）beta（3）上调有关，从而增强了抵抗力。这项审查说明了整合素α（v）beta（3）在肿瘤中的作用及其在非肿瘤疾病（如骨关节炎和心血管疾病）中的作用的复杂性。 （C）2015 Elsevier Masson SAS。版权所有。

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  • 来源
    《Medecine Nucleaire》 |2016年第1期|41-54|共14页
  • 作者

    Withofs N.; Hustinx R.;

  • 作者单位

    CHU Liege, Dept Med Phys, Nucl Med & Oncol Imaging Div, B35 Domaine Univ Sart Tilman, B-4000 Liege, Belgium;

    CHU Liege, Dept Med Phys, Nucl Med & Oncol Imaging Div, B35 Domaine Univ Sart Tilman, B-4000 Liege, Belgium;

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  • 正文语种 eng
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  • 关键词

    RGD; PET; Integrin; Angiogenesis;

    机译：RGD;PET;整合素;血管生成;

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