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.

精密医学需要可视化解剖细胞以实现诊断的工具，促进手术切除，并监测治疗反应。鉴定癌症和健康组织界面的技术需要对健康细胞具有特殊选择性照明癌细胞的能力。这也需要光学可以在体内选择性地阐明癌症的成像问题。迄今为止，用于分子光学染料用于临床前和临床成像研究由亲脂有机分子组成，水溶性有限，主要是肝清除概况，以“始终处于”状态为单位。这些重要的缺点动机研究替代的光学问题，暴露了改善水溶性和药代动力学与仅在感兴趣的目标时间内产生信号的能力。发光的灯笼复合物在第一个NIR（近红外）窗口中具有发射特性高度水溶性和生物相容性的替代品，可替代亲脂有机荧光团，主要是肝清除概况。发光灯笼的激发在250-350 nm的波长下最有效。尽管由此产生的有效的斯托克斯移位很大，短波长兴奋与不兼容 550–1000 nm的第一个生物学光学成像窗口。这阻止了离散的应用发光灯笼复合物作为迄今为止体内成像应用的光学问题。我们的小组有率先应用了放射线的Cherenkov辐射（CR）用于原位兴奋灯笼复合物。 Cr是由在带电颗粒发射下腐烂的同位素产生的培养基和最大强度低于400 nm。我们已经证明了发光的灯笼天线复合物是Cherenkov辐射介导的能量转移（CRET）的理想受体。在这里，我们提议设计和实施目标CRET灯笼问题，以形象形象癌症异质性体内多路复用，光学成像。