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）是用途最广泛的核医学成像方式。 原则上，它可以成像任何腐烂导致光子排放的放射线。有200多个 具有物理特性（半衰期，光子能量和产量）的光子发射器适用于使用医学成像 SPECT。在很大程度上，由于仪器的限制，医学中只有12个左右。我们建议 开发一个SPECT系统，该系统将大大扩大可能是候选者的放射线数量 医学成像。我们的基于CZT的系统将使成像光子能量的范围两倍。改善 Phototon能量分辨率以及空间分辨率超过两个以上（140 KEV的1.5％vs 10％，4至7 分别为10至15毫米）。灵敏度将提高超过10倍。当前的SPECT成像 技术不符合近期和潜在变革性进步的临床要求 放射药物治疗，治疗和精度医学。这些临床进步需要成像 严格定量，具有很高的空间分辨率，并且可以轻松成像多个放射线。 这些功能必须在当前成像时间的一小部分中提供。我们选择了设计规格 为了使设备满足α粒子的放射药物治疗的高度苛刻的成像需求 发射器（αRPT）。阿尔法发言人通过一个复杂的计划衰减，其中包括多个女儿；代理人是 令人难以置信的潜力使得治疗在亚GBQ施用的活性水平上有效。剂量法和 因此，在高空间分辨率下的定量准确性至关重要。我们将构建和描述“ alpha- 通过以下特定目的通过SPECT”摄像机：1。开发一个大面积3-D CZT成像光谱计 能够提供前所未有的能源分辨率；该检测器平台将是基本的构建块 对于alpha-spect。 2。将基于CZT的检测系统与合成化合物伽马相机结合起来 设计以实现在45厘米的广阔视野上具有超高分辨率的紧凑型检测系统 直径环。 3。开发针对高的定量多相关重建方法 Alpha-spect的性能能力。 4。评估幻像和大动物的系统性能 临床前研究。 5。在转移性前列腺癌中使用该系统进行病变和正常组织剂量法 接受镭223（XOFIGO）治疗的患者。该提案建立在无与伦比的合作伙伴关系基础上 仪器开发能力（Meng博士），再加上实施的尖端能力 多维图像生成的高级算法（Frey and du博士）将应用于 一种新的和承诺治疗的剂量测定要求（Sgouros博士），该治疗给高度潜在的辐射提供 传播癌细胞。除了推动拟议应用程序的特定临床情况之外 将实施的成像仪器技术是构建成像的重要第一步 可以在肿瘤学以及心脏病学和神经病学方面满足更广泛的临床需求的仪器。