Hyperspectral Single Photon Imaging of Targeted Alpha-Emitters

靶向α-发射体治疗(TAT)是一种新兴的肿瘤治疗方法。通过直接杀死癌症 细胞它不太容易产生抗药性。外照射联合放射治疗(XRT) TATS在治疗系统性疾病方面具有很高的潜力：XRT对少数 大肿瘤，以及小的、广泛传播的转移瘤的TAT。要了解目标行为和 在临床前和早期临床研究中需要剂量响应、剂量学信息。估计的 剂量分布对于TAT单独和与XRT结合的最佳计划至关重要。关于剂量的知识 TATS的分销可以帮助选择最有可能治疗的患者，从而缩短临床试验 要有效，并通过使用从以下方法获得的毒性知识缩短第一阶段剂量递增试验 XRT体验。放射性核素在体内的分布是估算TAT剂量分布的前提。 对于阿尔法排放国来说，有几个重大挑战。由于它们的高线性能量传递和结果 致命性，通常使用低剂量。此外，该光谱通常有许多低丰度的伽马射线。 分布在广泛的能量范围内，结合特征的x射线。典型的衰减链包括多个 子体放射性核素，重要的是估计它们的活度分布。这些能力将是 采用先进的SPECT系统，具有高灵敏度、高空间和能量分辨率。在这 在这个项目中，我们将开发阿尔法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，提供卓越的空间分辨率、超高灵敏度、 这些放射性核素在大型动物身上的出色能量分辨率。为实现这一目标，我们将推动走在前列 CZT探测器技术领先当前最先进的商用CZT伽马射线一代 探测器。我们将把这种基于CZT的探测系统与新型合成复眼伽马结合起来 相机设计，实现了α-SPECT系统。我们将开发定量重建方法和 基于Web的界面，用于此系统估算母体和子核素的分布。最后， 我们将使用体模和大型动物成像研究来评估该系统和重建方法 目前约翰霍普金斯大学正在开发TAT，以验证该系统。我们将在市场上进入 该系统通过约翰·霍普金斯大学作为癌症研究社区的核心服务，并通过Rapid， 有限责任公司，商业药物开发商。这个项目不仅将成为带来独特光谱的关键一步 为目前正在开发靶向放射性核素疗法的终端用户提供SPECT成像能力，但它也 将潜在地导致一种最先进的光谱-CZT探测器平台，供研究界使用，并 业界正在开发新一代临床SPECT仪器，用于超出目标的应用 放射性核素疗法。这个专题项目有一条明确的途径，为更广泛的最终用户提供服务。

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.