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（癌症放射性核素治疗）目的的 2 发射放射性核素通常能量足以在组织中放射性衰变后产生切伦科夫光。我们证明，这些2-粒子产生的光水平足以使用敏感的电荷耦合器件（CCD）相机在小鼠体内外部检测这些放射性核素，从而能够使用广泛使用的光学成像系统对2-发射放射性核素的分布进行体内成像。我们建议进一步表征和优化切伦科夫光在小动物体内分子成像中的使用，特别是涉及放射性核素疗法治疗癌症的应用。我们还将展示如何使用切伦科夫成像通过光学成像系统对 PET 放射性示踪剂的分布进行成像。研究将集中于三种放射性核素：18F（纯2-发射体）、90Y（纯2-发射体）和131I（同时发射2-粒子和伽马射线）。 90Y和131I在临床上均用作治疗性放射性核素。我们还建议开发 3 维切伦科夫发光断层扫描，并表明这与标准生物发光断层扫描有密切的关系。这项工作的意义在于，它首次允许对 90Y 等纯 2 发射放射性核素的分布进行灵敏的体内成像，并且还允许在简单且广泛使用的光学成像系统上对正电子发射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，并且可能具有某些临床应用，用于监测涉及 2 发射放射性核素的治疗，其中可以通过内窥镜到达目标部位。 公共卫生相关性： 用于诊断（正电子发射断层扫描）和治疗（癌症放射性核素治疗）目的的 2 发射放射性核素在组织中发生放射性衰变后会产生切伦科夫光。我们证明，光水平足以使用敏感的电荷耦合器件（CCD）相机进行外部检测，从而能够使用广泛使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，它允许对纯 2 发射放射性核素（例如 90Y）的分布进行灵敏的体内成像，并且还允许在简单的光学成像系统上对正电子发射放射性示踪剂进行成像。

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.