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

开发更灵敏、更准确的诊断试剂是实现更快、更准确的癌症诊断的重要一步。可以被引入体内以产生感兴趣的组织的视觉读数的试剂被称为成像探针。某些成像探针可以特异性地与肿瘤细胞结合，并发出特定波长的光，这些光可以被专门的成像设备检测到。这些探针被称为定向光学成像探针。一个理想的光学成像探针可以高精度地探测到皮肤表面下的一小群癌细胞。目前，大多数成像探针需要存在大量表面定位的肿瘤细胞，因此不是理想的光学成像探针。最近，来自石溪大学的Eszter Boros博士开发了一种基于稀土元素使用的灵敏光学成像探针的新方法。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性能。这项研究的长期目标是使用这些新的光学成像探针来可视化皮肤深处的少量肿瘤组织。作为与放射性制剂合作的专家，Boros博士致力于教育公众有关放射性的知识，并积极参与开发外展活动，与STEM教育研究所一起在为期一天的实验室课程中教育高中生关于放射性在安全，能源和医学应用中的重要性。来自石溪大学的Eszter Boros博士在化学部门化学结构、动力学和机制b项目的资助下，正在开发新的离散发光镧系化合物，这种化合物可以有效地用核医学中使用的放射性同位素发出的切伦科夫辐射激发。这种原位激发方法为增强深度穿透性和改善生物相容性的镧系光学成像探针铺平了道路。为了最大限度地提高镧系元素敏化天线的激发效率，在密度泛函理论（DFT）支持下，合成了离散铽和铕配合物的分子设计，使分子内切伦科夫发射放射性标签能够结合。除了提高铽（III）配合物的激发效率外，还寻求合成新的双功能螯合剂，以使敏化天线与铕（III）激发态的能量匹配更理想。这些优化的探针在体外可视化特定细胞表面受体的能力被用作切伦科夫辐射介导的镧系光探针激发的可行性的概念证明。作为一名致力于教育公众有关放射性的放射化学家，Boros博士正在为石溪大学STEM教育研究所的高中生开发一项全天实践核与放射化学科学模块的推广活动。该奖项反映了美国国家科学基金会的法定使命，并通过使用基金会的知识价值和更广泛的影响审查标准进行评估，被认为值得支持。

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.