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，当带电粒子在介电介质（如组织）中运动速度超过光速时，会发射光子。最近，我们和其他人发现，由于切伦科夫效应，可测量的可见光在体内服用？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方式的发展，称为切伦科夫发光成像（CLI），它允许标记为？利用灵敏的电荷耦合器件（CCD）相机在体内对放射性核素进行成像。这对于具有重要治疗作用的临床前研究尤其有价值。-释放放射性核素，如90Y，在示踪剂剂量下使用任何其他体内成像技术都不容易成像。CLI还提供了一种快速、低成本、易于获取的方法来对小动物的PET放射性示踪剂进行成像。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，或者使用内窥镜或基于导管的体内设备。正在探索的另一种可能的应用是利用放射性示踪剂产生的丰富的蓝色/UV切伦科夫光作为组织内部光激活的内部光传递源，例如在光动力治疗和光激活药物传递中。本提案的目标是提供切伦科夫发光的定量理解，因为它适用于生物医学应用，并产生数据，作为指导小动物和分子成像和治疗界的切伦科夫转化应用开发的平台。具体目标是通过计算/模拟、模拟实验和体内研究的结合，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，并确定检测极限。利用光谱信息进行切伦科夫层析成像的能力，以及在涉及切伦科夫和生物发光信号的多模态研究中进行光谱分解的能力，也将被描述。最后，我们将通过切伦科夫效应估计放射性示踪剂传递到组织的光能，以确定该机制是否可行地用作光激活的内部激发源。这项工作的预期结果是通过系统管理放射性示踪剂详细了解可见切伦科夫辐射的产生、分布和传输，这将作为基于这一新观察到的现象开发生物医学应用的关键基础。

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. PUBLIC HEALTH RELEVANCE: Radiotracers commonly administered for medical imaging examinations in nuclear medicine have recently been observed to emit detectable amounts of visible light via the Cerenkov effect. This opens up new opportunities for in vivo imaging of diagnostic and therapeutic radionuclides using sensitive optical imaging cameras, especially in preclinical small-animal studies. There also are prospects for using this Cerenkov radiation to assist in delivering light-activated therapies deep inside the body without the use of an external laser. This research in this proposal seeks to determine the feasibility of using Cerenkov light fo both imaging and therapeutic applications.