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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：
10876727
负责人：
Eszter Boros
金额：
$ 14.22万
依托单位：
UNIVERSITY OF WISCONSIN-MADISON
依托单位国家：
美国
项目类别：
财政年份：
2023
资助国家：
美国
起止时间：
2023-08-23 至 2024-12-31
项目状态：
已结题

来源：
https://reporter.nih.gov/project-details/10876727
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.

精准医疗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，监测治疗反应识别癌症和健康组织界面的技术需要能够以比健康细胞更高的选择性照射癌细胞。这也需要光学成像探针可以选择性地照亮体内癌症。到目前为止，分子光学染料用于临床前和临床成像研究包括具有有限水溶性的亲脂性有机分子，主要是肝清除率曲线，处于“始终开启”状态。这些重大缺陷促使研究了表现出改善的水溶性和药代动力学的替代光学探针，仅在目标组织中产生信号的能力。在第一NIR（近红外）窗口中具有发射性质的发光镧系元素络合物提供了一种发光材料，高水溶性和生物相容性的亲脂性有机荧光团的替代物，清除轮廓。发光镧系元素的激发在250-350 nm的波长下最有效。而所得到的有效斯托克斯位移很大，短波长激发与第一生物光学成像窗口为550-1000 nm。这就避免了应用离散的发光镧系元素络合物作为光学探针用于体内成像应用。我们集团开创了将放射性核素的切伦科夫辐射（CR）应用于离散的镧系元素配合物CR是由同位素在电介质中发射带电粒子的情况下衰变产生的介质，并表现出低于400 nm的最大强度。我们已经证明了发光镧系元素天线复合物是切伦科夫辐射介导的能量转移（CRET）的理想受体。这里我们建议设计和实施靶向CRET镧系元素探针，以成像癌症异质性，多路复用，体内光学成像。