Annotating Cancer Biology through Non-Invasive Molecular Imaging

通过非侵入性分子成像注释癌症生物学

• 批准号: 9816661
• 负责人: Jason S. Lewis
• 金额: $ 107.76万
• 依托单位: SLOAN-KETTERING INST CAN RESEARCH
• 依托单位国家: 美国
• 财政年份: 2019
• 资助国家: 美国
• 起止时间: 2019-09-04 至 2026-08-31
• 项目状态: 未结题
• 来源: https://reporter.nih.gov/project-details/9816661
• 关键词: Address; Area; Biology; Cancer Biology; Chemicals; Chemistry; Clinic; Development; Diagnosis; Discipline; Disease; Engineering; Foundations; Genomics; Human; Image; Imagery; Imaging technology; Label; Laboratories; Malignant Neoplasms; Measures; Medical Imaging; Methodology; Methods; Molecular; Monitor; Organism; Pathway interactions; Pharmacology; Phenotype; Radiochemistry; Techniques; Time; Tissues; Translating; Treatment outcome; Work; anatomic imaging; base; cancer imaging; cancer therapy; clinical translation; detector; imaging agent; improved; in vivo imaging; insight; molecular imaging; new therapeutic target; non-invasive imaging; novel; pre-clinical; predicting response; programs; response; theranostics; translational research program; tumor heterogeneity

ABSTRACT Molecular imaging (MI) originated in the need to better understand the fundamental molecular pathways inside organisms in a noninvasive manner. Over the past two decades, two factors have acted in concert to fuel the ascent of molecular imaging in both the laboratory and the clinic: (1) an increased understanding of the molecular mechanisms of disease and (2) the continued development of in vivo imaging technologies, ranging from improved detectors to novel labeling methodologies. We have established a vibrant and state-of-the-art laboratory-based translational research program. The Lewis lab portfolio is situated at the intersection of various disciplines – radiochemistry, cancer biology, chemistry, pharmacology and engineering. Our program has already demonstrated that our work is not just to generate an “image” but also to non-invasively and quantitatively measure target biology within a cancer. Even with the extensive preclinical advances in cancer imaging that we have accomplished and the unparalleled visualization of cancer biology we have achieved, our ability to translate our findings cannot be understated. Our program has excelled in the clinical translation of new imaging agents, providing new insights into cancer biology in humans. In the realms of this R35 we plan to focus on three main areas of discovery: (1) Can our successful imaging agents be transformed into theranostic agents with the ability to quantify the target through non-invasive imaging while providing concomitant lethality? (2) How can our theranostic agents be optimally deployed to quantitatively and non-invasively interrogate and treat tumor heterogeneity? (3) Following conventional and/or novel targeted therapies, can we image cancer-specific pathways to provide immediate and real-time predictors of response? We will exploit recent findings and novel methods to answer these questions, using an integrated set of imaging, chemical, genomic and cancer biology approaches. As such, the questions posed above will be of more general relevance and will allow us to address concepts related to the interactions between imaging, therapy, and response.

抽象的 分子成像 (MI) 起源于更好地了解内部基本分子通路的需要 以非侵入方式生物体。过去二十年来，有两个因素共同作用，推动了 分子成像在实验室和临床中的进步：（1）加深了对分子成像的了解 疾病的分子机制以及（2）体内成像技术的持续发展，包括 从改进的检测器到新颖的标记方法。我们建立了一个充满活力且最先进的 基于实验室的转化研究计划。刘易斯实验室组合位于各种领域的交叉点 学科——放射化学、癌症生物学、化学、药理学和工程学。我们的程序有 已经证明，我们的工作不仅仅是生成“图像”，而且是非侵入性和 定量测量癌症内的目标生物学。即使癌症的临床前研究取得了广泛的进展 我们已经完成的成像以及我们已经实现的癌症生物学无与伦比的可视化，我们的 转化我们的发现的能力不可低估。我们的项目在新药物的临床转化方面表现出色 成像剂，为人类癌症生物学提供新的见解。我们计划重点关注 R35 的领域 三个主要发现领域：（1）我们成功的成像剂能否转化为治疗诊断剂 是否有能力通过非侵入性成像量化目标，同时提供伴随的杀伤力？ (2) 如何 我们的治疗诊断药物能否最佳地部署来定量、非侵入性地询问和治疗肿瘤 异质性？ (3) 在传统和/或新型靶向治疗之后，我们可以对癌症特异性进行成像吗？ 提供即时和实时反应预测的途径？我们将利用最近的发现和新颖的 使用成像、化学、基因组和癌症生物学的综合方法来回答这些问题 接近。因此，上述问题将具有更普遍的相关性，并使我们能够解决 与成像、治疗和反应之间相互作用相关的概念。