Cherenkov luminescence mediated excitation of discrete lanthanide optical probes

切伦科夫发光介导的离散镧系元素光学探针的激发

基本信息

批准号：
10380890
负责人：
Eszter Boros
金额：
$ 4.45万
依托单位：
STATE UNIVERSITY NEW YORK STONY BROOK
依托单位国家：
美国
项目类别：
财政年份：
2021
资助国家：
美国
起止时间：
2021-04-01 至 2023-05-31
项目状态：
已结题

来源：
https://reporter.nih.gov/project-details/10380890
关键词：
Affinity Bilateral Binding Biodistribution Biological Bombesin Bombesin Receptor Carcinoma in Situ Cells Characteristics Charge Chemicals Cherenkov Radiation Clinical Complex Diagnosis Disease Disease Marker Dose Drug Kinetics Dyes Embryo Energy Transfer Europium Evaluation Excision Exhibits FOLH1 gene Generations Goals Hepatic Human In Situ In Vitro Investigation Ions Isotopes LNCaP Lanthanoid Series Elements Malignant Neoplasms Maximum Tolerated Dose Mediating Modeling Mole the mammal Molecular Monitor Mus Nature Operative Surgical Procedures Optics PC3 cell line Positron Positron-Emission Tomography Property Radioactive Radioisotopes Radiolabeled Signal Transduction Source Technology Terbium Tissues Toxic effect Tumor Markers Urea Visualization Visualization software Water analog biomaterial compatibility cancer cell cancer heterogeneity cancer imaging cancer therapy chromophore clinical imaging design detection limit fluorodeoxyglucose fluorophore imaging probe imaging study improved in vivo in vivo imaging in vivo optical imaging interest kidney cell lipophilicity luminescence multiplexed imaging optical imaging particle polypeptide precision medicine preclinical imaging prevent prostate cancer cell line quantum radiotracer treatment response tumor tumor xenograft uptake water solubility

项目摘要

Precision medicine requires tools that visualize diseased cells to enable diagnosis, facilitate surgical resection, and monitor therapeutic response. Technologies to identify the interface of cancer and healthy tissues require the ability to illuminate cancer cells with exceptional selectivity over healthy cells. This also requires optical imaging probes that can selectively illuminate cancer in vivo. To date, molecular optical dyes utilized for preclinical and clinical imaging studies are comprised of lipophilic organic molecules with limited water solubility, predominantly hepatic clearance profile, residing in an “always on” state. These significant drawbacks motivate investigation of alternative optical probes that exhibit improved water solubility and pharmacokinetics paired with the ability to produce signal only in the target tissues of interest. Luminescent lanthanide complexes with emissive properties in the first NIR (near-infrared) window provide a highly water soluble and biocompatible alternative to lipophilic organic fluorophores with predominantly hepatic clearance profiles. Excitation of luminescent lanthanides is most efficient at wavelengths of 250–350 nm. While the resulting, effective Stokes-shift of is conveniently large, the short-wavelength excitation is incompatible with the first biological optical imaging window of 550–1000 nm. This has prevented application of discrete luminescent lanthanide complexes as optical probes for in vivo imaging applications to date. Our group has pioneered the application of Cherenkov radiation (CR) of radionuclides for the in situ excitation of discrete lanthanide complexes. CR is produced by isotopes decaying under emission of charged particles in dielectric media and exhibits a maximum intensity below 400 nm. We have demonstrated that luminescent lanthanide antenna complexes are ideal acceptors for Cherenkov radiation-mediated energy transfer (CRET). Here, we propose to devise and implement targeted CRET lanthanide probes to image cancer heterogeneity with multiplexed, optical imaging in vivo.

精准医学需要能够可视化病变细胞的工具，以实现诊断、促进手术切除、并监测治疗反应需要识别癌症和健康组织界面的技术。与健康细胞相比，能够以优异的选择性照射癌细胞。这也需要光学。迄今为止，分子光学染料可用于选择性地照亮体内癌症。临床前和临床成像研究由水溶性有限的亲脂性有机分子组成，主要是肝脏清除率，处于“始终开启”状态。研究表现出改善的水溶性和药代动力学的替代光学探针仅在感兴趣的目标组织中产生信号的能力。在第一个 NIR（近红外）窗口中具有发射特性的发光稀土配合物提供了高度水溶性和生物相容性，可替代亲脂性有机荧光团（主要为肝脏）发光镧系元素的激发在 250–350 nm 的波长下最有效。由此产生的有效斯托克斯位移非常大，短波长激发与第一个 550-1000 nm 的生物光学成像窗口阻碍了离散技术的应用。迄今为止，我们的团队已经将发光稀土配合物作为体内成像应用的光学探针。率先应用放射性核素的切伦科夫辐射（CR）来原位激发离散 CR 是由同位素在电介质中带电粒子发射下衰变产生的。介质并表现出低于 400 nm 的最大强度。天线复合体是切伦科夫辐射介导能量转移（CRET）的理想受体。建议设计并实施靶向 CRET 镧系元素探针，以利用以下方法对癌症异质性进行成像：体内多重光学成像。