Hyperspectral Single Photon Imaging of Targeted Alpha-Emitters

目标阿尔法发射器的高光谱单光子成像

• 批准号: 10633193
• 负责人: Yong Du
• 金额: $ 58.21万
• 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: 2021-07-01 至 2025-03-31
• 项目状态: 未结题
• 来源: https://reporter.nih.gov/project-details/10633193
• 关键词: 3-Dimensional; Academia; Acceleration; Actinium; Alpha Particles; Animals; Area; Behavior; Biological Response Modifier Therapy; Canada; Canis familiaris; Characteristics; Clinical; Clinical Research; Clinical Trials; Collaborations; Communities; Complex; Custom; DCNU; Data; Daughter; Detection; Development; Diagnostic; Discipline of Nuclear Medicine; Distributional Activity; Dose; Engineering; Ensure; External Beam Radiation Therapy; Family suidae; Gamma Cameras; Gamma Rays; Generations; Goals; Growth; Image; Industry; Industry Collaboration; Interdisciplinary Study; Isotopes; Knowledge; Letters; Linear Energy Transfer; Manufacturer; Marketing; Measures; Medical Imaging; Memorial Sloan-Kettering Cancer Center; Methods; Modality; Monkeys; Neoplasm Metastasis; Online Systems; Organ; Oryctolagus cuniculus; Parents; Pathway interactions; Patient Selection; Performance; Pharmaceutical Preparations; Pharmacologic Substance; Phase; Photons; Physics; Polishes; Predisposition; Radioisotopes; Radionuclide Imaging; Radionuclide therapy; Radiopharmaceuticals; Research; Research Personnel; Resistance development; Resolution; Roentgen Rays; Services; System; Systemic disease; Techniques; Technology; Therapeutic; Tissue imaging; Toxic effect; Universities; Work; animal imaging; anticancer research; cancer cell; cancer therapy; clinical imaging; clinical translation; compound eye; design; detection platform; detector; dosimetry; experience; flexibility; image reconstruction; imaging capabilities; imaging detector; imaging study; imaging system; improved; in vivo; instrumentation; manufacture; next generation; novel; pre-clinical; reconstruction; response; single photon emission computed tomography; success; targeted imaging; technology development; tumor; web based interface

Targeted alpha-emitter therapy (TAT) is an emerging modality in the cancer therapy. By directly killing cancer cells it is less susceptible to development of resistance. Combination of external beam radiation therapy (XRT) and TATs have a high potential for treatment of systemic disease: the XRT is effective for a small number of large tumors, and the TAT for small, widely disseminated metastases. To understand the targeting behavior and dose response, dosimetry information is required in preclinical and early-stage clinical studies. Estimates of the dose distribution are essential for optimal planning of TAT alone and combined with XRT. Knowledge of the dose distribution from TATs could shorten clinical trials by helping select patients for whom the therapy is most likely to be effective, and by shortening Phase 1 dose escalation trials by using knowledge of toxicities obtained from XRT experience. The distribution of the radionuclide in vivo is a prerequisite for estimating TAT dose distribution. For alpha emitters, there are several significant challenges. Due to their high linear energy transfer and resulting lethality, low doses are commonly used. Also, the spectrum typically has many low-abundance gamma rays spread over a wide energy range combined with characteristic x-rays. Typical decay chains include multiple daughter radionuclides, and it is important to estimate their activity distributions. These capabilities would be enabled by an advanced SPECT system with high sensitivity and high spatial and energy resolution. In this project, we will develop the Alpha-SPECT system, a novel scanner aimed at imaging of these radionuclides. It uses advanced spectroscopic CZT imaging detectors to provide excellent spatial resolution, ultrahigh sensitivity, and excellent energy resolution of these radionuclides in large animals. To achieve this, we will push the forefront of CZT detector technology a generation ahead of the current state-of-art commercial CZT-based gamma-ray detectors. We will combine this CZT-based detection system with the novel synthetic compound-eye gamma camera design to realize the Alpha-SPECT system. We will develop quantitative reconstruction methods and web-based interface for this system to estimate the distribution of the parent and daughter radionuclides. Finally, we will evaluate the system and reconstruction method using phantom and large animal imaging studies using TATs that are currently under development at Johns Hopkins to validate the system. We will market access to the system as a core service to the cancer research community through Johns Hopkins and, through Rapid, LLC, to commercial drug developers. This project will not only serve as a critical step to bring the unique spectral SPECT imaging capability to end users who are currently developing targeted radionuclide therapies, but it also will potentially lead to a state-of-art spectral-CZT detector platform for use by the research community and industry in developing the next generation clinical SPECT instrumentations for applications beyond targeted radionuclide therapies. This prosed project has a clear pathway to serve a much broader spectrum of end-users.

靶向α发射体疗法（TAT）是癌症治疗中的一种新兴方式。直接杀死癌症 细胞不易产生耐药性。结合外照射放射治疗 (XRT) TAT 具有治疗全身性疾病的巨大潜力：XRT 对少数患者有效 大肿瘤的 TAT 和小而广泛播散的转移瘤的 TAT。了解目标行为并 临床前和早期临床研究需要剂量反应、剂量测定信息。的估计 剂量分布对于单独 TAT 以及与 XRT 结合的最佳规划至关重要。剂量知识 TAT 的分发可以帮助选择最有可能接受治疗的患者，从而缩短临床试验时间 为了有效，并通过利用从以下来源获得的毒性知识来缩短第一阶段剂量递增试验 XRT 经验。放射性核素在体内的分布是估计 TAT 剂量分布的先决条件。 对于阿尔法发射体来说，存在几个重大挑战。由于它们的高线性能量传递和由此产生的 致死率高，常用低剂量。此外，光谱通常有许多低丰度伽马射线 与特征 X 射线相结合，分布在很宽的能量范围内。典型的衰变链包括多个 子放射性核素，估计它们的活度分布很重要。这些能力将是 由具有高灵敏度、高空间和能量分辨率的先进 SPECT 系统实现。在这个 项目中，我们将开发 Alpha-SPECT 系统，这是一种旨在对这些放射性核素进行成像的新型扫描仪。它 采用先进的光谱CZT成像探测器，提供优异的空间分辨率、超高灵敏度、 这些放射性核素在大型动物体内具有出色的能量分辨率。为了实现这一目标，我们将走在最前沿 CZT 探测器技术比当前最先进的基于 CZT 的商用伽马射线领先一代 探测器。我们将把这种基于 CZT 的检测系统与新型合成复眼伽马相结合 相机设计实现Alpha-SPECT系统。我们将开发定量重建方法和 该系统基于网络的界面来估计母体和子体放射性核素的分布。最后， 我们将使用模型和大型动物成像研究来评估系统和重建方法 约翰霍普金斯大学目前正在开发 TAT 来验证该系统。我们将进入市场 该系统作为通过约翰霍普金斯大学和Rapid为癌症研究界提供的核心服务， LLC，商业药物开发商。该项目不仅是带来独特光谱的关键一步 SPECT 成像能力为目前正在开发靶向放射性核素疗法的最终用户提供，但它也 可能会产生一个最先进的光谱 CZT 探测器平台，供研究界使用 行业正在开发下一代临床 SPECT 仪器，用于超出目标的应用 放射性核素疗法。这个项目有一个明确的途径来服务更广泛的最终用户。

项目成果

Experimental Evaluation of a 3-D CZT Imaging Spectrometer for Potential Use in Compton-Enhanced PET Imaging.

3-D CZT 成像光谱仪在康普顿增强 PET 成像中的潜在用途的实验评估。

• 发表时间: 2023-01
• 作者: Jin, Yifei;Streicher, Michael;Yang, Hao;Brown, Steven;He, Zhong;Meng, Ling
• 通讯作者: Meng, Ling

Experimental validation of a rodent PET scanner prototype based on a single LYSO crystal tube.

基于单个 LYSO 晶体管的啮齿动物 PET 扫描仪原型的实验验证。

• 发表时间: 2022-07
• 作者: Freire, Marta;Gonzalez;Cañizares, Gabriel;Rezaei, Ahmadreza;Nuyts, Johan;Berr, Stuart S;Williams, Mark B;Benlloch, Jose M;Gonzalez, Antonio J
• 通讯作者: Gonzalez, Antonio J