Hyperspectral Single Photon Imaging of Targeted Alpha-Emitters

靶向α-发射体治疗（达特）是一种新兴的癌症治疗方式。通过直接杀死癌症 细胞，它是不太容易发展的阻力。联合外照射放射治疗（XRT） 和TAT具有治疗全身性疾病的高潜力：XRT对少数患者有效。 大的肿瘤，达特用于小的、广泛扩散的转移。为了了解目标行为， 剂量反应，在临床前和早期临床研究中需要剂量测定信息。估计 剂量分布对于达特单独和与XRT组合的最佳计划是必不可少的。剂量知识 TAT的分布可以通过帮助选择最有可能接受治疗的患者来缩短临床试验 有效，并通过使用从以下研究中获得的毒性知识缩短I期剂量递增试验 XRT体验。放射性核素在体内的分布是估算达特剂量分布的前提。 对于α发射体来说，有几个重大的挑战。由于它们的高线性能量转移和产生的 致死性，通常使用低剂量。此外，光谱通常有许多低丰度的伽马射线 分布在很宽的能量范围内并结合特征X射线。典型的衰变链包括多个 子体放射性核素，重要的是要估计它们的活动分布。这些能力将是 通过具有高灵敏度以及高空间和能量分辨率的先进SPECT系统实现。在这 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 使用先进的光谱CZT成像探测器，提供出色的空间分辨率，高灵敏度， 以及这些放射性核素在大型动物体内的出色能量分辨率。为实现这一目标，我们将推动最前沿 的CZT探测器技术，比目前最先进的商用CZT伽马射线探测器技术领先一代。 探测器我们将联合收割机这种基于CZT的检测系统与新的合成复眼伽马 摄像头设计，实现Alpha-SPECT系统。我们将开发定量重建方法， 基于网络的界面，该系统估计母和子放射性核素的分布。最后， 我们将使用体模和大型动物成像研究评估系统和重建方法， 目前正在约翰霍普金斯开发的TAT来验证该系统。我们将市场准入， 通过约翰霍普金斯和Rapid， 有限责任公司，商业药物开发商。该项目不仅将作为一个关键步骤，使独特的光谱 SPECT成像能力的最终用户谁目前正在开发有针对性的放射性核素治疗，但它也 将有可能导致一个最先进的光谱CZT探测器平台，供研究界使用， 行业开发下一代临床SPECT仪器的应用超出了目标 放射性核素治疗。这个项目有一个明确的途径，以服务于更广泛的最终用户。

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.