High Energy and Spatial Resolution Multi-Isotope SPECT Imaging of Targeted Alpha-Emitters and their Daughters

目标α发射体及其子体的高能量和空间分辨率多同位素 SPECT 成像

• 批准号: 10470322
• 负责人: Yong Du
• 金额: $ 71.74万
• 依托单位: JOHNS HOPKINS UNIVERSITY
• 依托单位国家: 美国
• 财政年份: 2021
• 资助国家: 美国
• 起止时间: 2021-09-01 至 2026-05-31
• 项目状态: 未结题
• 来源: https://reporter.nih.gov/project-details/10470322
• 关键词: 3-Dimensional; Algorithms; Alpha Particle Emitter; Animals; Area; Automobile Driving; Caliber; Canada; Cancer Patient; Cardiology; Characteristics; Clinical; Clinical Research; Communicable Diseases; Communities; Complex; Consent; Coupled; DCNU; Daughter; Development; Devices; Diagnosis; Discipline of Nuclear Medicine; Distributional Activity; Dose; Ensure; Evaluation; Fostering; Gamma Cameras; Gamma Rays; Generations; Grant; Growth; Half-Life; Image; Imaging technology; Industry; Institutional Review Boards; Interdisciplinary Study; Investigation; Isotopes; Knowledge; Lead; Lesion; Manufacturer Name; Medical Imaging; Medicine; Metastatic Prostate Cancer; Methods; Modality; Neurology; Normal tissue morphology; Oncology; Organ; Parents; Patients; Performance; Photons; Physics; Property; Protocols documentation; Radiation; Radiation exposure; Radioisotopes; Radiopharmaceuticals; Radium; Research; Research Personnel; Resolution; Rheumatology; Roentgen Rays; Role; Scheme; System; Techniques; Technology; Thick; Time; Toxic effect; Universities; base; bone; cancer cell; cancer therapy; clinical imaging; clinical translation; compound eye; design; detection platform; detector; dosimetry; experience; image reconstruction; imaging modality; improved; instrumentation; kidney cortex; next generation; precision medicine; preclinical study; quantitative imaging; reconstruction; routine imaging; single photon emission computed tomography; standard of care; success; targeted imaging; theranostics; treatment planning; tumor; uptake

Single photon emission computed tomography (SPECT) is the most versatile nuclear medicine imaging modality. In principle, it can image any radionuclide whose decay leads to photon emissions. There are more than 200 photon emitters with physics properties (half-life, photon energy and yield) appropriate for medical imaging using SPECT. In large part due to instrumentation constraints, only 12 or so are used in medicine. We propose to develop a SPECT system that will vastly expand the number of radionuclides that could be candidates for medical imaging. Our CZT-based system will double the range of imageable photon energies; improve the photon energy resolution and also the spatial resolution more than two-fold (1.5% vs 10% at 140 keV and 4 to 7 vs 10 to 15 mm respectively). The sensitivity will be increased more than 10-fold. Current SPECT imaging technology does not meet the clinical demands of recent and potentially transformative advances in radiopharmaceutical therapy, theranostics and precision medicine. These clinical advances require imaging that is rigorously quantitative, has a high spatial resolution and can simultaneously image more than one radionuclide. These capabilities must be offered at a fraction of current imaging times. We have chosen design specifications for the device to meet the highly demanding imaging needs of radiopharmaceutical therapy with alpha-particle emitters (αRPT). Alpha-emitters decay via a complex scheme that includes multiple daughters; the agents are incredibly potent such that treatment is effective at sub GBq administered activity levels. Dosimetry and, therefore quantitative accuracy at high spatial resolution is essential. We will build and characterize the “alpha- SPECT” camera via the following specific aims: 1. Develop a large area 3-D CZT imaging-spectrometer that is capable of providing an unprecedented energy resolution; this detector platform will be the basic building block for alpha-SPECT. 2. Combine the CZT-based detection system with a synthetic compound-eye gamma camera design to achieve a compact detection system with ultrahigh resolution over a wide field of view in a 45 cm diameter ring. 3. Develop quantitative multi-isotope reconstruction methods that are tailored to the high performance capability of Alpha-SPECT. 4. Evaluate system performance in phantoms and in large animal preclinical studies. 5. Use the system for lesion and normal tissue dosimetry in metastatic prostate cancer patients treated with Radium-223 (Xofigo). The proposal is founded on a partnership of unparalleled instrumentation development capability (Dr. Meng), coupled with cutting-edge capability in implementing advanced algorithms for multi-dimensional image generation (Drs. Frey and Du) that will be applied to the dosimetry demands (Dr. Sgouros) of a new and promising treatment that delivers highly potent radiation to disseminated cancer cells. Beyond the specific clinical scenario that is driving the proposed application, the imaging instrumentation technology that will be implemented is a significant first step to building imaging instrumentation that will serve much broader clinical needs in oncology and also in cardiology and neurology.

单光子发射计算机断层扫描 (SPECT) 是最通用的核医学成像方式。 原则上，它可以对任何衰变导致光子发射的放射性核素进行成像。有超过200个 具有适合医学成像的物理特性（半衰期、光子能量和产量）的光子发射器 SPECT。很大程度上由于仪器限制，只有 12 种左右用于医学。我们建议 开发一种 SPECT 系统，该系统将大大增加可能成为候选的放射性核素的数量 医学成像。我们基于 CZT 的系统将使可成像光子能量范围加倍；改善 光子能量分辨率和空间分辨率超过两倍（1.5% vs 10%，140 keV 和 4 至 7 分别为 10 至 15 毫米）。灵敏度将提高10倍以上。当前 SPECT 成像 技术不能满足近期和潜在变革性进展的临床需求 放射药物治疗、治疗诊断学和精准医学。这些临床进展需要成像 是严格定量的，具有高空间分辨率，可以同时对多种放射性核素进行成像。 这些功能必须以当前成像时间的一小部分提供。我们选择了设计规格 使设备能够满足α粒子放射性药物治疗的高要求成像需求 发射器（αRPT）。阿尔法发射体通过包含多个子体的复杂方案衰减；代理人是 令人难以置信的效力，使得治疗在低于 GBq 的活动水平下有效。剂量测定和， 因此，高空间分辨率下的定量精度至关重要。我们将构建并表征“阿尔法- SPECT”相机通过以下具体目标： 1. 开发大面积 3-D CZT 成像光谱仪 能够提供前所未有的能量分辨率；该探测器平台将成为基本构建块 用于 α-SPECT。 2. 将基于 CZT 的检测系统与合成复眼伽马相机相结合 旨在实现 45 厘米宽视野内具有超高分辨率的紧凑型检测系统 直径环。 3. 开发适合高通量的定量多同位素重建方法 Alpha-SPECT 的性能能力。 4. 评估模型和大型动物中的系统性能 临床前研究。 5. 使用该系统对转移性前列腺癌的病变和正常组织进行剂量测定 接受 Radium-223 (Xofigo) 治疗的患者。该提案建立在无与伦比的合作伙伴关系的基础上 仪器仪表开发能力（孟博士），加上尖端的实施能力 用于多维图像生成的高级算法（Frey 和 Du 博士）将应用于 剂量测定需要（Sgouros 博士）一种新的、有前途的治疗方法，可以向患者提供高效的辐射 扩散的癌细胞。除了推动所提出的应用程序的特定临床场景之外， 将要实施的成像仪器技术是构建成像的重要第一步 仪器将满足肿瘤学、心脏病学和神经学领域更广泛的临床需求。