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: 10471612
• 负责人: Jason S. Lewis
• 金额: $ 14.37万
• 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/10471612
• 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.

摘要 分子成像（MI）起源于需要更好地了解内部的基本分子通路 以非侵入性的方式。在过去的二十年里，有两个因素共同推动了 分子影像学在实验室和临床上的发展：（1）对分子影像学的认识增加， 疾病的分子机制和（2）体内成像技术的持续发展， 从改进的检测器到新颖的标记方法。我们已经建立了一个充满活力和最先进的 以实验室为基础的转化研究计划。刘易斯实验室产品组合位于各种 放射化学、癌症生物学、化学、药理学和工程学。我们的计划 已经证明，我们的工作不仅仅是生成一个“图像”，而且是非侵入性的， 定量测量癌症内的靶生物学。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和我们已经实现的癌症生物学的无与伦比的可视化，我们的 翻译我们调查结果的能力不能低估。我们的项目在临床翻译新的 成像剂，为人类癌症生物学提供新的见解。在R35的领域中，我们计划将重点放在 在三个主要领域的发现：（1）我们成功的成像剂可以转化为治疗诊断剂 能够通过非侵入性成像量化目标，同时提供伴随的致命性？(2)如何 我们的治疗诊断剂是否可以最佳地用于定量和非侵入性地询问和治疗肿瘤 异质性？(3)在常规和/或新型靶向治疗后，我们能否对癌症特异性 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的 方法来回答这些问题，使用一套综合的成像，化学，基因组学和癌症生物学 接近。因此，上述问题将具有更广泛的相关性，并将使我们能够解决 与成像、治疗和反应之间的相互作用相关的概念。