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: 10249950
• 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/10249950
• 关键词: Address; Area; Biology; Cancer Biology; Chemicals; Chemistry; Clinic; Development; Diagnosis; Discipline; Disease; Engineering; Foundations; Genomics; Human; Image; 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; Visualization; 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途径 生物体以无创的方式。在过去的二十年中，有两个因素共同采取了行动，以助长 实验室和诊所的分子成像的上升：（1）对 疾病的分子机制和（2）体内成像技术的持续发展，范围 从改进的探测器到新型标记方法。我们已经建立了一个充满活力和最先进的 基于实验室的翻译研究计划。刘易斯实验室投资组合位于各种交集 学科 - 放射化学，癌症生物学，化学，药理学和工程。我们的计划有 已经证明我们的工作不仅是为了生成“图像”，而且是非侵入性的 定量测量癌症中的靶向生物学。即使在癌症方面取得了广泛的临床前进展 我们已经完成的成像以及我们已经实现的癌症生物学的无与伦比的可视化 翻译我们的发现的能力不能低估。我们的计划在新的临床翻译方面非常出色 成像剂，提供有关人类癌症生物学的新见解。在此R35领域，我们计划集中精力 在发现的三个主要领域：（1）我们成功的成像剂可以转化为theranoticatic剂 具有通过非侵入性成像来量化目标的能力，同时提供伴随的杀伤力？ （2）如何 我们的治疗剂可最佳地部署到定量和非侵入性询问和治疗肿瘤 异质性？ （3）遵循常规和/或新颖的靶向疗法，我们可以对癌症特异性图像成像 提供响应的立即和实时预测指标的途径？我们将利用最新发现和新颖 使用一组集成的成像，化学，基因组和癌症生物学的方法来回答这些问题 方法。因此，上面的问题将具有更普遍的相关性，并使我们能够解决 与成像，治疗和反应之间的相互作用有关的概念。