Cherenkov luminescence mediated excitation of discrete lanthanide optical probes

精密医学需要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。识别癌症和健康组织界面的技术需要 照亮癌细胞的能力比健康细胞具有特殊的选择性。这也需要光学 可以选择性地照亮体内癌症的成像探针。到目前为止，分子光学染料用于 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， 主要是肝脏清除情况，处于“始终打开”状态。这些重大缺陷促使 具有更好的水溶性和药代动力学的替代光学探针的研究 仅在感兴趣的目标组织中产生信号的能力。 在第一近红外(近红外)窗口中具有发射性质的发光稀土络合物提供了 以肝脏为主的亲脂性有机荧光团的高水溶性和生物相容性替代 净空纵断面。在250-350 nm波长范围内，稀土发光材料的激发效率最高。而当 由此产生的有效斯托克斯位移很大，短波长激发与 第一个550-1000 nm的生物光学成像窗口。这阻碍了离散的应用 到目前为止，发光稀土络合物作为光学探针用于活体成像应用。我们的团队已经 率先将放射性核素的切伦科夫辐射(CR)应用于离散原子的原位激发 稀土络合物。铬是由带电粒子在介质中发射时衰变的同位素产生的。 介质，在400 nm以下表现出最大强度。我们已经证明了发光的稀土元素 天线复合体是切伦科夫辐射介导的能量转移(CRET)的理想受体。在这里，我们 建议设计和实施有针对性的稀土元素探针，以成像癌症异质性 多路传输，体内光学成像。

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.