Annotating Cancer Biology through Non-Invasive Molecular Imaging

摘要 分子成像(MI)起源于需要更好地了解体内的基本分子途径 以一种非侵入性的方式。在过去的二十年里，两个因素共同作用，推动了 分子成像在实验室和临床上的进展：(1)对分子成像的认识增加 疾病的分子机制和(2)活体成像技术的持续发展，测距 从改进的检测器到新的标记方法。我们已经建立了一个充满活力和最先进的 以实验室为基础的翻译研究计划。刘易斯实验室的产品组合位于各种 学科--放射化学、癌症生物学、化学、药理学和工程学。我们的节目有 已经证明，我们的工作不仅仅是为了产生一种“形象”，而且是为了非侵入性和 定量测量癌症内的靶生物学。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 翻译我们的发现的能力不能被低估。我们的项目在新词的临床翻译方面表现出色 显像剂，为人类癌症生物学提供新的见解。在这款R35的领域里，我们计划专注于 关于三个主要领域的发现：(1)我们成功的显像剂能否转化为治疗药物 有能力通过非侵入性成像来量化目标，同时提供伴随的杀伤力？(2)如何 我们的治疗药物能否被优化配置，以定量和非侵入性地询问和治疗肿瘤 异质性？(3)在传统和/或新的靶向治疗之后，我们能想象癌症特异性吗？ 提供即时和实时反应预测的途径？我们将利用最新的发现和新的 使用一套综合的成像、化学、基因组和癌症生物学来回答这些问题的方法 接近了。因此，上面提出的问题将具有更广泛的相关性，并将使我们能够处理 与成像、治疗和反应之间的相互作用相关的概念。

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.