Quantitative Evaluation of Cerenkov Luminescence for Imaging and Therapy

描述（由申请人提供）：切伦科夫辐射是一种现象，其中当带电粒子在诸如组织的电介质中以比光速更快的速度移动时发射可见光子。最近，我们和其他人发现，由于切伦科夫效应，在体内给药后产生了可测量的可见光。向小动物释放放射性核素。此外，产生可检测信号所需的注射活性的量与小动物分子成像应用一致。这一观察结果导致了一种新的混合分子成像模式的发展，称为切伦科夫发光成像（CLI），它允许用？发射放射性核素，使用灵敏的电荷耦合器件（CCD）照相机在体内成像。这对于具有重要治疗作用的临床前研究尤其有价值。发射放射性核素，例如90 Y，其不能使用任何其它体内成像技术在示踪剂剂量下容易地成像。CLI还提供了一种快速，低成本，易于获得的方法来成像PET放射性示踪剂在小动物。切伦科夫发光的转化机会也存在。CLI可能用于皮肤、眼睛和口腔，或使用体内的内窥镜或基于导管的设备。正在探索的另一种可能的应用是使用由放射性示踪剂产生的丰富的蓝色/UV切伦科夫光作为用于光活化的组织内部深处的内部光递送源，例如在光动力治疗和光活化药物递送中。该提案的目标是提供对Cerenkov发光的定量理解，因为它适用于生物医学应用，并产生数据，作为指导分子成像和治疗界开发小动物和翻译Cerenkov应用的平台。具体目标是通过计算/模拟、体模实验和体内研究的组合，获得对切伦科夫信号和光谱的详细定量理解。我们将比较两种不同的相机技术检测弱切伦科夫信号的性能，并确定检测限。利用光谱信息的能力，切伦科夫层析成像，并在多模态研究，涉及切伦科夫和生物发光信号的光谱解混，也将被表征。最后，我们将估计通过切伦科夫效应由放射性示踪剂传递到组织的光能，以确定这种机制是否可以可行地用作光活化的内部激发源。这项工作的预期成果是详细了解系统管理的放射性示踪剂的可见切伦科夫辐射的生产，分布和运输，这将作为一个重要的基础上，开发基于这种新观察到的现象的生物医学应用。

DESCRIPTION (provided by applicant): Cerenkov radiation is a phenomenon in which optical photons are emitted when a charged particle moves faster than the speed of light in a dielectric medium such as tissue. Recently we, and others, have discovered that measurable visible light due to the Cerenkov effect is produced in vivo following administration of ?-emitting radionuclides to small animals. Furthermore, the amounts of injected activity required to produce a detectable signal are consistent with small animal molecular imaging applications. This observation has led to the development of a new hybrid molecular imaging modality known as Cerenkov luminescence imaging (CLI) that allows the spatial distribution of biomolecules labeled with ?-emitting radionuclides to be imaged in vivo using sensitive charge-coupled device (CCD) cameras. This is especially valuable for preclinical studies with important therapeutic ?-emitting radionuclides, such as 90Y, that cannot readily be imaged at tracer doses using any other in vivo imaging technique. CLI also provides a fast, low-cost, readily accessible approach to image PET radiotracers in small animals. Translational opportunities for Cerenkov luminescence also exist. CLI might be possible for skin, eye and oral cavity, or using endoscopic or catheter-based devices inside the body. Another possible application that is being explored is to use the abundant blue/UV Cerenkov light produced by radiotracers as a source of internal light delivery deep inside tissues for photoactivation, for example in photodynamic therapy and photoactivated drug delivery. The goal of this proposal is to provide a quantitative understanding of Cerenkov luminescence as it applies to biomedical applications and to produce data that serves as a platform for guiding the development of small-animal and translational Cerenkov applications by the molecular imaging and therapeutics community. The specific aims address obtaining a detailed quantitative understanding of Cerenkov signals and spectra that can be measured from tissues through a combination of computation/simulation, phantom experiments and in vivo studies. We will compare the performance of two different camera technologies for the detection of weak Cerenkov signals, and determine detection limits. The ability to exploit spectral information for Cerenkov tomography, and for spectral unmixing in multimodal studies that involve both Cerenkov and bioluminescence signals, also will be characterized. Finally, we will estimate the light energy delivered to tissues by radiotracers via the Cerenkov effect, to determine if this mechanism can feasibly be used as a source of internal excitation for photoactivation. The anticipated outcome of this work is a detailed understanding of the production, distribution and transport of visible Cerenkov radiation by systemically-administered radiotracers, that will serve as a critical foundation on which to develop biomedical applications based on this newly-observed phenomenon.