In Vivo Optical Imaging of Beta-Emitting Radionuclides using Cerenkov Radiation

描述(由申请人提供)： 用于诊断(正电子发射断层扫描，PET)和治疗(癌症的放射性核素治疗)目的的2-发射放射性核素通常具有足够的能量，在组织中的放射性衰变后产生切伦科夫光。我们证明，这些2-粒子产生的光级足以使用灵敏的电荷耦合器件(CCD)相机在老鼠体内对这些放射性核素进行外部检测，从而能够使用广泛可用的光学成像系统在体内成像2-发射放射性核素的分布。我们建议进一步表征和优化切伦科夫光在活体小动物分子成像中的使用，特别是在涉及放射性核素疗法治疗癌症的应用中。我们还将展示如何使用切伦科夫成像来使用光学成像系统对PET放射性示踪剂的分布进行成像。研究将集中在三种放射性核素上，18F(纯2-粒子发射体)，90Y(纯2-发射体)和131I(同时发射2-粒子和伽马射线)。~(90)Y和~(131)I都是临床上使用的治疗性核素。我们还提出了发展三维切伦科夫发光层析成像，并表明这与标准的生物发光层析成像有密切的关系。这项工作的意义在于，它首次允许在体内灵敏地成像纯2发射放射性核素(如90Y)的分布，并允许在简单且广泛可用的光学成像系统上对发射正电子的放射性示踪剂进行成像。我们认为切伦科夫光成像将成为临床前分子成像和治疗研究的一种强大的新成像方法，并可能在监测涉及2发射放射性核素的治疗方面有一定的临床应用，其中靶点可以通过内窥镜进入。 公共卫生相关性： 2-用于诊断(正电子发射断层扫描)和治疗(癌症中的放射性核素治疗)目的的放射性核素在组织中的放射性衰变后产生切伦科夫光。我们证明，使用灵敏的电荷耦合器件(CCD)相机进行外部探测时，光级足以用于外部探测，因此可以使用广泛可用的光学成像系统对这些放射性核素的分布进行成像。这一发现的意义在于，它允许在体内灵敏地成像纯2发射放射性核素的分布，如90Y，它还允许在简单的光学成像系统上成像发射正电子的放射性示踪剂。

DESCRIPTION (provided by applicant): 2-emitting radionuclides used for diagnostic (positron emission tomography, PET) and therapeutic (radionuclide therapy in cancer) purposes are typically energetic enough to produce Cerenkov light subsequent to their radioactive decay in tissue. We demonstrate that the light levels produced by these 2- particles are sufficient for external detection of these radionuclides in a mouse using a sensitive charge- coupled device (CCD) camera, thus enabling the distribution of 2-emitting radionuclides to be imaged in vivo using widely available optical imaging systems. We propose to further characterize and optimize the use of Cerenkov light for in vivo small animal molecular imaging, especially for applications involving radionuclide therapies to treat cancer. We also will show how Cerenkov imaging can be used to image the distribution of PET radiotracers using an optical imaging system. Studies will focus on three radionuclides, 18F (a pure 2+ emitter), 90Y (a pure 2- emitter) and 131I (emits both 2--particles and gamma rays). Both 90Y and 131I are clinically used as therapeutic radionuclides. We also propose to develop 3-dimensional Cerenkov luminescence tomography, and show that this has a close relationship to standard bioluminescence tomography. The significance of this work is that for the first time, it allows the distribution of pure 2-emitting radionuclides such as 90Y to be imaged sensitively in vivo, and it also permits the imaging of positron-emitting radiotracers on simple, and widely available optical imaging systems. We think imaging of Cerenkov light will be a powerful new imaging methodology for preclinical molecular imaging and therapeutic studies, and may have certain clinical applications for monitoring therapies involving 2-emitting radionuclides where the target sites can be accessed endoscopically. PUBLIC HEALTH RELEVANCE: 2-emitting radionuclides used for diagnostic (positron emission tomography) and therapeutic (radionuclide therapy in cancer) purposes produce Cerenkov light subsequent to their radioactive decay in tissue. We demonstrate that the light levels are sufficient for external detection using a sensitive charge-coupled device (CCD) camera, thus enabling the distribution of these radionuclides to be imaged using widely available optical imaging systems. The significance of this discovery is that it allows the distribution of pure 2-emitting radionuclides, such as 90Y, to be imaged sensitively in vivo, and it also permits the imaging of positron-emitting radiotracers on simple optical imaging systems.