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

单光子发射计算机断层扫描(SPECT)是目前应用最广泛的核医学成像技术。 原则上，它可以成像任何衰变导致光子发射的放射性核素。有200多个 具有适用于医学成像的物理特性(半衰期、光子能量和产额)的光子发射器 SPECT。在很大程度上，由于仪器设备的限制，只有12种左右的药物用于医学。我们建议 开发一种SPECT系统，它将极大地增加可能成为 医学成像。我们基于CZT的系统将使可成像光子能量的范围扩大一倍；改善 光子能量分辨率以及两倍以上的空间分辨率(在140keV和4至7千伏时为1.5%比10% 分别为10至15 mm)。灵敏度将提高10倍以上。当前SPECT成像 技术不能满足最近的和潜在的变革性进展的临床需求 放射药物治疗、声学治疗和精确医学。这些临床进展需要成像 它是严格定量的，具有高空间分辨率，可以同时成像一种以上的放射性核素。 这些功能必须在当前成像时间的一小部分内提供。我们已经选择了设计规格 为了满足阿尔法粒子放射药物治疗的高要求成像需求 发射器(αRpt)。阿尔法发射器通过一个包括多个子体的复杂方案进行衰变； 令人难以置信的强大，以至于治疗在亚GBQ管理的活动水平是有效的。剂量学和， 因此，高空间分辨率下的定量精度是至关重要的。我们将建立并描述“阿尔法-- SPECT“相机通过以下具体目标：1.研制大面积三维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的构建块 进行α-SPECT检查。2.将基于CZT的探测系统与合成复眼伽马相机相结合 设计实现了一个紧凑的探测系统，在45厘米的宽视场内具有超高分辨率 直径环。3.开发适合于高密度的定量多同位素重建方法 Alpha-SPECT的性能。4.评估系统在幻影和大型动物中的性能 临床前研究。5.使用该系统进行转移性前列腺癌病变和正常组织的剂量测量 用~(223)Re治疗的患者。这项提议是建立在无与伦比的 仪器开发能力(孟博士)，加上在执行 用于多维图像生成的高级算法(Frey和Du博士)，将应用于 剂量学要求(Sgouros博士)找到一种新的、有希望的治疗方法，将高度有效的辐射传递到 播散性癌细胞。除了推动拟议应用程序的特定临床场景之外， 将实施的成像仪器技术是构建成像的重要第一步 该仪器将服务于肿瘤学以及心脏病学和神经病学更广泛的临床需求。

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.