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

开发更灵敏和更准确的诊断试剂是朝着更快和更准确的癌症诊断迈出的重要一步。可以被引入体内以产生感兴趣组织的可视读数的试剂被称为成像探针。某些成像探针可以与肿瘤细胞特异性结合，并在特殊成像设备可以检测到的特定波长发出光。这些探针被称为靶向光学成像探针。理想的光学成像探头甚至可以高精度地探测皮肤表面深处的一小部分癌细胞。目前，大多数成像探头需要大量位于表面的肿瘤细胞存在，因此不是理想的光学成像探头。最近，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测器的新方法。在这个项目中，博罗斯博士致力于优化这些放射性成像探测器的性能。这项研究的长期目标是使用这些新的光学成像探测器来可视化皮肤深处的少量肿瘤组织。作为放射性试剂工作的专家，Boros博士致力于教育公众有关放射性的知识，并积极参与开展外展活动，在STEM教育研究所为期一天的实验室课程中教育高中生放射性在安全、能源和医学应用中的重要性。在化学系化学结构、动力学和机制B项目的资助下，来自石溪大学的Eszter Boros博士正在开发新的离散发光稀土络合物，该络合物可以通过用于核医学的放射性同位素发出的切伦科夫辐射有效地激发。这种原位激发方法为增强深度穿透和改善生物相容性的稀土光学成像探针铺平了道路。为了最大限度地提高稀土敏化天线的激发效率，在密度泛函理论(DFT)的支持下，合成了离散的Tb和Eu配合物的分子设计，使分子内的切伦科夫辐射标记得以并入。除了提高Tb(III)配合物的激发效率外，人们还致力于合成新的双功能螯合剂，以将敏化天线与Eu(III)激发态更理想的能量匹配结合在一起。这些优化的探针在体外显示特定的细胞表面受体的能力被用作切伦科夫辐射介导的稀土光学探针激发的可行性的概念验证。作为一名致力于教育公众放射性知识的放射化学家，Boros博士正在与石溪大学STEM教育研究所合作，为高中生开发一项为期一天的亲身实践核与放射化学科学模块的外展活动。该奖项反映了NSF的法定使命，并通过使用基金会的智力优势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.