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）是最通用的核医学成像方式。 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 具有适用于医学成像的物理特性（半衰期、光子能量和产率）的光子发射器， SPECT。在很大程度上由于仪器的限制，只有12个左右用于医学。我们建议 开发一个SPECT系统，这将大大增加可能成为候选者的放射性核素的数量。 医学成像我们的基于CZT的系统将使可成像光子能量的范围增加一倍; 光子能量分辨率和空间分辨率超过两倍（1.5%对10%，在140 keV和4至7 vs分别为10至15 mm）。灵敏度将提高10倍以上。当前SPECT成像 技术不符合最近和潜在的变革性进展的临床需求， 放射性药物治疗、治疗诊断学和精确医学。这些临床进展需要成像， 严格定量，具有高空间分辨率，并可同时对一种以上放射性核素成像。 这些功能必须在当前成像时间的一小部分提供。我们选择了设计规格 对于该装置来说，满足使用α粒子的放射性药物治疗的高要求的成像需求 发射体（αRPT）。α-发射体通过一个复杂的方案衰变，该方案包括多个子体; 令人难以置信的效力，使得治疗在低于GBq的施用活性水平下有效。剂量测定和， 因此，在高空间分辨率下的定量准确性是至关重要的。我们将建立并描述“阿尔法- SPECT”相机通过以下具体目的：1.研制了大面积三维CZT成像光谱仪， 能够提供前所未有的能量分辨率;这个探测器平台将是基本的构建块 阿尔法SPECT。2.将基于CZT的检测系统与合成复眼伽马相机联合收割机相结合 设计实现了一个紧凑的检测系统，在45 cm的宽视场内具有100%的分辨率 直径环。3.开发定量多同位素重建方法， Alpha-SPECT的性能。4.在体模和大型动物中评价系统性能 临床前研究。5.将该系统用于转移性前列腺癌的病变和正常组织剂量测定 用镭-223（Xofigo）治疗的患者。该提案是建立在一个无与伦比的伙伴关系， 仪器开发能力（孟博士），加上尖端的能力，在实施 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（斯古罗斯博士）一种新的和有前途的治疗，提供高度有效的辐射， 扩散的癌细胞除了推动拟议应用的特定临床场景外， 将要实施的成像仪器技术是建立成像系统的重要的第一步 这将为肿瘤学以及心脏病学和神经病学提供更广泛的临床需求。

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.