Ultra-Low Count Quantitative SPECT for Alpha-Particle Therapies

用于 α 粒子治疗的超低计数定量 SPECT

• 批准号: 10446871
• 负责人: Abhinav K Jha
• 金额: $ 52.62万
• 依托单位: WASHINGTON UNIVERSITY
• 依托单位国家: 美国
• 财政年份: 2022
• 资助国家: 美国
• 起止时间: 2022-09-30 至 2026-06-30
• 项目状态: 未结题
• 来源: https://reporter.nih.gov/project-details/10446871
• 关键词: Acceleration; Actinium; Address; Alpha Particle Emitter; Alpha Particles; Anatomy; Androgen Antagonists; Biological Markers; Biopsy; Clinical; Clinical Trials; Collaborations; Collimator; Computer Models; Cytotoxic Chemotherapy; DCNU; Data; Daughter; Disease; Dose; Dose-Limiting; Engineering; Evaluation; Gamma Rays; Generations; Goals; Gold; Image; Intestinal Content; Intestines; Isotopes; Joints; Lesion; Measures; Methods; Modeling; Modernization; Noise; Organ; Outcome; Patients; Performance; Photons; Physics; Physiology; Process; Protocols documentation; Quality of life; Radiation; Radiation Oncology; Radiation Tolerance; Radiation therapy; Radioisotopes; Radiopharmaceuticals; Radium; Regimen; Resistance; Risk; Safety; Scanning; Schedule; Serum; Site; Skeleton; System; Techniques; Therapeutic; Thorium; Time; Treatment Protocols; Work; adverse event monitoring; base; bone; cancer cell; castration resistant prostate cancer; clinical efficacy; clinical imaging; clinical translation; clinically significant; clinically translatable; detector; drug development; drug efficacy; efficacy evaluation; first-in-human; imaging approach; imaging study; improved; improved outcome; individualized medicine; industry partner; innovation; men; non-invasive imaging; novel; particle therapy; radiation absorbed dose; reconstruction; simulation; single photon emission computed tomography; therapy outcome; treatment planning; tumor; uptake; virtual clinical trial

PROJECT SUMMARY: The overall goal of this project is to develop and comprehensively validate ultra-low count quantitative SPECT (ULC-QSPECT) methods for alpha particle radiopharmaceutical therapies (αRPTs), including in a first-in-man trial in patients with bone metastatic castration-resistant prostate cancer. αRPTs, such as those based on Actinium-225, Thorium-227 and approved Radium-223 isotopes, are an emerging class of cytotoxic therapies for patients with disseminated metastatic disease using internally administered alpha-particle emitting agents. Despite the great potential of these therapies, current αRPT regimens are not personalized, with administered activity dependent merely on mass, likely leading to non-optimal therapy. To address this challenge, there is a crucial unmet need for methods to measure the isotope uptake, and hence the absorbed radiation dose with these therapies, both at sites of disease and in vital dose-limiting organs. SPECT provides a clinically translatable mechanism to achieve this goal. However, a key challenge to SPECT-based quantification is that the administered activities in αRPTs are orders of magnitude lower than a typical SPECT scan, leading to ultra-low detected count levels. Conventional approaches to quantification that reconstruct the isotope distribution and estimate the regional uptake from reconstructed images are erroneous at these low count levels. To address this issue, we put forwards a novel computational ULC-QSPECT framework for regional activity estimation from αRPTs. These methods quantify regional uptake directly from projection data skipping the reconstruction step, and at the same time, extract the maximal possible information from the acquired projection data. For this purpose, we propose novel methods that accurately model the physics of imaging αRPTs, including stray- radiation-related noise, use data from multiple-energy windows, incorporate scatter-window photons for quantification, and process data in list-mode format. Our extensive preliminary data show that the proposed methods result in nearly unbiased uptake and variances close to the theoretical limit. We propose to further develop and rigorously evaluate these methods. Our proposed evaluations include studies over multiple scanners with different detectors and different collimator configurations. Further, our goal is clinical translation of these methods. Towards this goal, we propose to clinically evaluate these methods for measuring activity concentrations at sites of uptake of [223Ra]RaCl2 in men with castrate resistant prostate cancer. These methods will enable quantification of activity at disease sites in the skeleton as well as clearance through the intestine. The approach has direct relevance to patients as it achieves noninvasive imaging of low-administered activity therapies. Further, this proposal has substantial potential impact to improve both safety and efficacy of drug development efforts in this rapidly evolving space. Further, the methods developed in this proposal will strengthen the clinical utility of SPECT in managing patients with these therapies.

项目摘要： 该项目的总体目标是开发和全面验证超低计数定量SPECT （ULC-QSPECT）α粒子放射性药物疗法（αRPTS）的方法，包括 骨转移性持续性前列腺癌患者的试验。 αRpts，例如基于 Actinium-225，Thorium-227和批准的镭223同位素是一类新兴的细胞毒性疗法 对于使用内部施用的α粒子发射剂的传播转移性疾病的患者。 尽管这些疗法具有巨大的潜力，但当前的αRPT方案未经个性化，并给予 活动仅取决于质量，可能导致非最佳治疗。为了应对这一挑战，有一个 对测量同位素摄取的方法的关键需求，因此吸收的辐射剂量与 这些疗法，无论是在疾病部位还是在重要的剂量限制器官中。 SPECT提供临床翻译 实现这一目标的机制。但是，基于SPECT的量化的关键挑战是 αRPT中的施用活性比典型的SPECT扫描低几个数量级，导致超低 检测到计数水平。常规的数量方法，重建同位素分布和 在这些低计数水平下，从重建图像中估算区域吸收是错误的。解决 这个问题，我们提出了一个新颖的计算ULC-Qspect框架，用于从 αrpts。这些方法直接从投影数据跳过重建步骤中量化区域摄取， 同时，从获得的投影数据中提取最大可能的信息。为了这 目的，我们提出了新的方法，可以准确地模拟成像αRpps的物理学，包括流浪 与辐射相关的噪声，使用来自多能窗口的数据，并包含散点窗户照片 数量和以列表模式格式处理数据。我们广泛的初步数据表明提议 方法导致几乎没有偏见的吸收和差异接近理论极限。我们建议进一步 开发和严格评估了这些方法。我们提出的评估包括对多个的研究 带有不同检测器和不同准准仪配置的扫描仪。此外，我们的目标是临床翻译 这些方法。为了实现这一目标，我们建议在临床上评估这些方法以测量活动 castrate抗性前列腺癌男性的[223RA] RACL2摄取部位的浓度。这些方法 将实现骨骼中疾病部位的活动以及通过肠道清除。 该方法与患者具有直接相关性，因为它可以实现低管理活性的无创成像 疗法。此外，该提案对提高药物的安全性和效率具有巨大的潜在影响 在这个快速发展的空间中的发展工作。此外，本提案中开发的方法将 加强SPECT在管理这些疗法患者中的临床实用性。