CAREER: Exploring Cherenkov Radiation for the In Situ Excitation of Discrete Luminescent Lanthanide Complexes

职业：探索切伦科夫辐射对离散发光稀土配合物的原位激发

• 批准号: 2337429
• 负责人: Eszter Boros
• 金额: $ 67.5万
• 依托单位: University of Wisconsin-Madison
• 依托单位国家: 美国
• 项目类别: Continuing Grant
• 财政年份: 2023
• 资助国家: 美国
• 起止时间: 2023-10-01 至 2025-10-31
• 项目状态: 未结题
• 来源: https://www.nsf.gov/awardsearch/showAward?AWD_ID=2337429&HistoricalAwards=false
• 关键词: CAREER; Exploring; Cherenkov; Radiation; Situ

Developing more sensitive and accurate diagnostic agents is an important step towards the faster and more accurate diagnosis of cancer. Agents that can be introduced to the body to produce a visual readout of the tissues of interest are called imaging probes. Certain imaging probes can specifically bind to tumor cells and emit light at specific wavelengths that can be detected by specialized imaging equipment. These probes are called targeted optical imaging probes. An ideal optical imaging probe can detect even a small population of cancer cells with high accuracy, deep under the surface of the skin. Currently, most current imaging probes require the presence of large amounts of superficially located tumor cells and therefore are not ideal optical imaging probes. Recently, Dr. Eszter Boros from Stony Brook University has developed a new approach to sensitive optical imaging probes that is based on the use of rare earth elements. In this project, Dr. Boros is working to optimize the properties of these radioactive imaging probes. The long-term goal of this research is to use these new optical imaging probes to visualize small amounts of tumor tissue deep under the skin. As an expert in work with radioactive agents, Dr. Boros is dedicated to educating the public about radioactivity and is actively engaged in developing outreach activities that educate high school students in a one-day laboratory course with the Institute for STEM Education about the significance of radioactivity in safety, energy, and medicine applications.With funding from the Chemical Structure, Dynamics and Mechanisms-B Program of the Chemistry Division, Dr. Eszter Boros from Stony Brook University is developing new discrete luminescent lanthanide complexes that can be efficiently excited with Cherenkov radiation emitted by radioactive isotopes utilized in nuclear medicine. This in situ excitation method paves the way for lanthanide-based optical imaging probes with enhanced depth penetration and improved biocompatibility. To maximize the excitation efficiency of the lanthanide-sensitizing antenna, density functional theory (DFT)-supported molecular designs of discrete terbium and europium complexes are synthesized that enable the incorporation of intramolecular, Cherenkov-emissive radiolabels. In addition to improving the excitation efficiency of terbium(III) complexes, the synthesis of new bifunctional chelators is pursued to incorporate sensitizing antennas with a more ideal energy match for europium(III) excited states. The ability of these optimized probes to visualize specific cell surface-receptors in vitro is used as a proof-of-concept for the feasibility of Cherenkov-radiation mediated excitation of lanthanide based optical probes. As a radiochemist dedicated to educating the public about radioactivity, Dr. Boros is developing an outreach activity in the form of a full day, hands-on Nuclear and Radiochemistry science module for high school students with the Institute for STEM Education at Stony Brook University.This award reflects NSF's statutory mission and has been deemed worthy of support through evaluation using the Foundation's intellectual merit and broader impacts review criteria.

开发更灵敏，更准确的诊断剂是朝着更快，更准确诊断癌症的重要一步。可以引入人体以产生感兴趣组织的视觉读数的药物称为成像探针。某些成像探针可以特异性结合肿瘤细胞，并在可以通过专用成像设备检测到的特定波长处发出光。 这些探针称为靶向光学成像探针。理想的光学成像探针甚至可以在皮肤表面深处以高精度检测到少量的癌细胞。目前，大多数当前的成像探针都需要大量的表面肿瘤细胞，因此不是理想的光学成像探针。最近，来自Stony Brook University的Eszter Boros博士开发了一种新的方法来基于使用稀土元素的使用敏感光学成像探针。在这个项目中，Boros博士正在努力优化这些放射性成像探针的特性。这项研究的长期目标是使用这些新的光学成像探针可视化皮肤深处的少量肿瘤组织。 As an expert in work with radioactive agents, Dr. Boros is dedicated to educating the public about radioactivity and is actively engaged in developing outreach activities that educate high school students in a one-day laboratory course with the Institute for STEM Education about the significance of radioactivity in safety, energy, and medicine applications.With funding from the Chemical Structure, Dynamics and Mechanisms-B Program of the Chemistry Division, Dr. Eszter Boros from Stony Brook University is developing new离散发光的灯笼复合物可以通过在核医学中使用的放射性同位素发出的Cherenkov辐射有效激发。这种原位激发方法为基于兰烷的光学成像探针铺平了道路，并具有增强的深度穿透和提高的生物相容性。为了最大程度地提高灯笼敏感天线的激发效率，合成了离散terbium和Europium复合物的密度功能理论（DFT）支持的分子设计，可以合成，从而掺入分子内分子，Cherenkov-Cherenkov- cherenkov- cherenkov- cherenkov-cherenkov--和Cherenkov。除了提高Terbium（III）配合物的激发效率外，还要选择新的双功能螯合剂的合成，以将敏感性的天线与Europium（III）激发态更理想的能量匹配结合起来。这些优化探针在体外可视化特定细胞表面受体受体的能力被用作概念概念，以证明基于兰谷的光学探针的Cherenkov辐射介导的激发的可行性。作为一名致力于向公众提供放射性教育的放射性化学家，Boros博士正在以全天的形式开发一项宣传活动，动手实践核和放射化学科学模块，该模块在斯托尼·布鲁克大学（Stony Brook University）的STEM教育研究所（Stony Brook University）的高中学生中。该奖项颁发了NSF的法定任务，反映了通过评估基金会的支持者，并通过基金会的范围进行了评估和宽广的支持。