Synthesis and evaluation of small-molecule imaging agents

小分子显像剂的合成与评价

• 批准号: 8763576
• 负责人: Martin Schnermann
• 金额: $ 109.05万
• 依托单位: DIVISION OF BASIC SCIENCES - NCI
• 依托单位国家: 美国
• 资助国家: 美国
• 起止时间: 至
• 项目状态: 未结题
• 来源: https://reporter.nih.gov/project-details/8763576
• 关键词: Area; Biological Factors; Biological Process; Biology; Cells; Chemicals; Clinical Trials; Collaborations; Development; Evaluation; FDA approved; Fluorescence; Goals; Image; Indocyanine Green; Life; Link; Malignant Neoplasms; Medicine; Microscopy; Molecular; New Agents; Pharmaceutical Chemistry; Property; Role; Staging; Techniques; cancer diagnosis; cancer therapy; chemical stability; cyanine; design; fluorophore; imaging modality; improved; in vivo; interest; optical imaging; small molecule

The discovery and implementation of molecularly targeted imaging modalities has progressed considerably in recent years. Our interest centers on the design and synthesis of near-IR fluorophores, which are employed extensively in microscopy and in vivo optical imaging. One such agent, indocyanine green, is FDA approved and currently involved in over 100 active clinical trials, including over 20 for cancer diagnosis. Despite a central role in modern biology and medicine, the compounds employed in near-IR fluorescence techniques have changed little in recent decades. Using molecular design concepts borrowed from related fields (e.g. medicinal chemistry and natural product synthesis), we seek to develop new agents with improved utility for cancer-related imaging. Specifically, we are developing near-IR fluorophores, especially in the cyanine class, with improved fluorescence properties and chemical stability. At this stage, the focus of the lab centers on the development of concise, modular synthetic approaches to target molecules. We have identified a new target-fluorophore linking strategy that imparts dramatically improved stability. The compounds we prepare will be applied in a variety of contexts to enable improved readout of biological processes, particularly in the area of cancer diagnosis. We have developed key collaborations (Mitchell and Krishna) to enable our small molecule synthesis-oriented group to evaluate our agents in in vivo settings.

近年来，分子靶向成像方式的发现和实施取得了长足的进展。我们的兴趣集中在近红外荧光团的设计和合成上，这些荧光团广泛用于显微镜和体内光学成像。其中一种药剂是吲哚烷绿色，已获得FDA批准，目前参与了100多次活跃的临床试验，其中包括20多个用于癌症诊断。尽管在现代生物学和医学中起着核心作用，但近几十年来，近红外荧光技术中采用的化合物几乎没有改变。使用从相关领域借用的分子设计概念（例如药物化学和天然产物合成），我们试图开发具有改善与癌症相关成像的实用性的新代理。具体而言，我们正在开发近红外荧光团，尤其是在氰基类别中，具有改善的荧光性能和化学稳定性。在此阶段，实验室的重点集中在简明的，模块化的合成方法的靶向分子上。我们已经确定了一种新的目标 - 荧光团连接策略，该策略可显着提高稳定性。我们准备的化合物将在各种情况下应用，以改善生物学过程的读数，尤其是在癌症诊断领域。我们已经开发了关键的合作（Mitchell和Krishna），以使我们的小分子合成群体能够在体内环境中评估我们的代理。