The molecular imaging decoding human 组织 in health and disease

简介: In order to bring new medicines to patients faster and more effectively, we have to improve our understanding of the diseases we want to treat. 利用先进的分子成像技术-最近由质谱技术推动-澳门第一赌城在线娱乐的科学家能够深入和详细地探测和分析组织样本，这在以前是不可能的. By harnessing the incredible powers of AI and machine learning, 完整的分子复杂性终于可以被破译，并且已经揭示了有可能从根本上改变未来药物发现和开发的见解.

How molecular understanding of diseases is helping evaluate drug safety

现代药物发现的关键是能够尽可能详细地了解澳门第一赌城在线娱乐的化合物在细胞水平上对人体组织的影响. In other words, exactly what our candidate drugs are doing in a patient’s body. 几十年来,, scientists have used the traditional techniques of histology and histopathology, staining 组织 samples and looking for particular cellular morphologies, markers and signals on microscope slides. To work out where drug molecules go within the body (biodistribution), previously the only available option was autoradiography, 这是一种昂贵且费力的无线电标记方法，仅能对单个目标进行图像分布.

现在, 一套创新技术构成了澳门第一赌城在线娱乐先进的分子成像能力，使澳门第一赌城在线娱乐在了解疾病过程和评估药物疗效和安全性方面的能力有了巨大的飞跃. These technologies let us probe every 组织 sample – whether from patient biopsies, animal models or advanced cell cultures – in unprecedented depth. 将这些非凡的探测能力与人工智能(AI)和机器学习令人难以置信的分析和解释能力相结合，意味着澳门第一赌城在线娱乐可以在寻找未知和意外的过程中以开放的心态探索未知领域.

Navigating the human body’s molecular complexity with mass spectrometry imaging

In this field, advances in mass spectrometry imaging (MSI) have been the real game changer. 澳门第一赌城在线娱乐现在可以用质谱仪同时测量单个分子的质量, to visualise their spatial distributions – whether peptides, 蛋白质, 脂质, endogenous metabolites or drug molecules – within the microenvironment of a 组织, 为它们之间的相互关系提供了重要线索，使澳门第一赌城在线娱乐能够更好地评估化合物的安全性和有效性.

Mass spectrometry itself is of course not new. Utilised in many areas of research and development, it relies on the process of ionisation: turning 组织 samples into gaseous form. MSI的特殊之处在于组织样品在电离之前没有均匀(混合). 而不是, it is snap-frozen and ionised directly from its intact surface, so that each molecule’s original position is known. 整个样品一次扫描几微米，分析每个离散位置，形成澳门第一赌城在线娱乐最终生成的图像中的一个像素. This provides a wealth of digital information.

Creating a ‘Google Earth’ view

当今先进的分子成像技术——尤其是微星成像技术——意味着澳门第一赌城在线娱乐现在可以绘制出有史以来最详细的分子图谱. 就像谷歌地球一样，软件可以将地球的卫星视图缩小到单个街道和建筑物的3D视图, our new imaging capabilities allow us to zoom in and out from the micro to the macro level and back. 澳门第一赌城在线娱乐的质谱仪甚至可以让澳门第一赌城在线娱乐通过窗户看到沙发在哪里.

Every molecule we detect has its own map, pieced together by tens of thousands of images from different perspectives. 澳门第一赌城在线娱乐可以“看到”药物分子, 生物标志物和组织微环境同时进行，并从基因组和分子的角度到细胞的角度检查图像, 组织, 器官和患者水平. Vast datasets are generated from healthy, 患病和药物处理过的组织样本，然后可以通过人工智能和机器学习技术挖掘这些样本，以发现模式, connections and relationships at a level of complexity far greater than ever before, turning information into insights and insights into knowledge. 

Armed with this knowledge we’ll be more equipped to design safe and effective drugs, develop optimal drug delivery methods, work out appropriate dosing and monitor disease progression. Using these approaches, we are already uncovering new insights such as:

• 这是对肠道微生物产生的代谢物如何在帕金森病等神经系统疾病中发挥作用的首次机制描述¹
• The mechanism of nutrient sensing and utilisation in lung metastasis² 结肠直肠癌³
• A novel 3D lung adenocarcinoma model that can mimic the 在活的有机体内 组织 and the tumour microenvironmennt⁴
• 临床前成像以探索肿瘤候选药物穿过血脑屏障的渗透及其对脑肿瘤生长的影响⁵
• 纳米药物分布的高分辨率3D可视化为肿瘤血管和微环境对纳米药物定位的影响提供了有价值的见解⁶

The Cancer Research UK ‘Grand Challenge’

AstraZeneca is part of an innovative five-year multi-centre, 多学科合作，旨在绘制恶性肿瘤分子景观的最详细的地图.

Funded by Cancer Research UK (CRUK), 这项“大挑战”由国家物理实验室的约瑟芬·邦奇教授领导，该联盟包括弗朗西斯·克里克研究所的主要科学家, the Beatson Institute in Glasgow, the University of 剑桥 and many others.

该团队的数据库将向全世界的研究人员开放，其创建方法也将标准化, best-practice guidance for deployment of the latest technologies.

与学术界合作是澳门第一赌城在线娱乐突破科学界限、推动疾病发现和理解、帮助澳门第一赌城在线娱乐创造下一代治疗方法的关键.

参考文献

1. 微生物衍生的肉毒碱模拟物是以前未知的肠脑轴通讯介质- 2020年3月11日;6(11):eaax6328. doi: 10.1126 / sciadv.aax6328. 
2. ilc2驱动的先天免疫检查点机制拮抗NK细胞在肺中的抗转移功能- 2020 Sep;21(9):998-1009. doi: 10.1038/s41590-020-0745-y
3. The amino acid transporter SLC7A5 is required for efficient growth of KRAS-mutant colorectal cancer. Nat Genet 53, 16-26 (2021). http://doi.org/10.1038/s41588-020-00753-3
4.  聚合三维细胞培养模型的多模态质谱成像表征- 2020年9月15日;92(18):12538-12547. doi: 10.1021 / acs.analchem.0c02389. 
5. 奥西替尼与其他EGFR TKIs的血脑屏障(BBB)通透性的临床前比较- 2020年10月7日;临床.1871.2019. doi: 10.1158/1078-0432.ccr - 19 - 1871. 
6. High-resolution 3D visualization of nanomedicine distribution in tumors - 2020 Jan 1;10(2):880-897. doi: 10.7150 / thno.37178.