Alpha-emitter Imaging for Dosimetry and Treatment Planning

用于剂量测定和治疗计划的阿尔法发射体成像

• 批准号: 10713710
• 负责人: Yong Du
• 金额: $ 45.04万
• 依托单位: JOHNS HOPKINS UNIVERSITY
• 依托单位国家: 美国
• 财政年份: 2023
• 资助国家: 美国
• 起止时间: 2023-09-19 至 2028-08-31
• 项目状态: 未结题
• 来源: https://reporter.nih.gov/project-details/10713710
• 关键词: 3-Dimensional; Address; Adopted; Alpha Particle Emitter; Alpha Particles; Area; Biological Response Modifier Therapy; Characteristics; Clinical; Clinical Trials; Collaborations; Complex; Data; Data Collection; Daughter; Development; Diagnostic Imaging; Diagnostic Procedure; Discipline of Nuclear Medicine; Disseminated Malignant Neoplasm; Distributional Activity; Dose; Drug Kinetics; Gamma Rays; Goals; Histologic; Image; Knowledge; Linear Energy Transfer; Maximum Tolerated Dose; Measures; Methodology; Methods; Modality; Modeling; Monitor; Organ; Outcome; PET/CT scan; Patient Selection; Patient-Focused Outcomes; Patients; Phase; Photons; Physics; Procedures; Program Research Project Grants; Property; Protocols documentation; Radiobiology; Radioisotopes; Radiopharmaceuticals; Resistance; Surface; System; Techniques; Testing; Time; Tissues; Toxic effect; Treatment Efficacy; Treatment Protocols; Uncertainty; Validation; Work; X-Ray Computed Tomography; absorption; animal data; animal-assisted therapy; cancer cell; cancer therapy; chemotherapy; clinical practice; cost; design; dosimetry; image reconstruction; imaging modality; improved; improved outcome; in vivo; individualized medicine; member; optical spectra; patient population; patient response; patient screening; quantitative imaging; reconstruction; response; screening; single photon emission computed tomography; therapy outcome; treatment optimization; treatment planning; tumor

Radiopharmaceutical therapy with α-particle emitters (αRPT) is a highly effective cancer therapy modality; it delivers potent alpha-particle radiation to cancer cells and is therefore not susceptible to resistance seen with most other cancer therapies. It is also unique in that alpha-emitters also emit photons that can be imaged by nuclear medicine modalities. This allows for patient-specific treatment planning and optimization of patient therapy. These unique features of αRPT have not been used, however, because αRPT is so effective that the activity used to treat patient is too low to be imaged with conventional nuclear medicine imaging methods. In this project we will develop and implement accurate single photon emission computed tomography (SPECT) imaging methods that overcome this limitation. Our hypothesis is that enabling quantitative αRPT imaging and making it convenient so that it is widely adopted will improve the outcome of patients treated with αRPT. The distribution of the radionuclide in vivo is a prerequisite for estimating the absorbed dose distributions needed to plan and optimize αRPT’s. There are several significant challenges to imaging the distribution of α-emitters in patients. Due to their high linear energy transfer (LET) and resulting lethality, low administered activities are used. Typical decay chains include multiple daughter radionuclides that emit photons, and it is important to also determine their activity distribution. Also, the photon emission spectrum for α-emitters typically has many low-abundance gamma rays spread over a wide energy range. These properties have made imaging-based dosimetry difficult; the imaging that has been performed has not been quantitatively rigorous. We propose to develop imaging reconstruction methods applicable to clinical SPECT systems that will account for the complex imaging physics and allow for validated quantitative SPECT imaging of αRPT for accurate dosimetry calculations. The overall goal is to incorporate such quantitative SPECT imaging into a clinically implementable imaging workflow that can provide accurate dosimetry for treatment planning and efficacy monitoring. Our group, in collaboration with members of a Hopkins startup company, Radiopharmaceutical Imaging and Dosimetry, LLC (Rapid), have already made considerable progress on SPECT imaging of αRPT agents. In Aim1, we will extend this work to develop quantitative reconstruction methods for SPECT imaging of alpha emitters that produce accurate measures of activity distribution for dosimetry which will also be useful for SPECT diagnostic imaging in general. Another challenge for imaging αRPT is the requirement that patients return for several imaging sessions to obtain the needed pharmacokinetics in normal organs and tumors. Thus, in Aim 2 we will investigate the trade-off between number of imaging time-points and the accuracy of dosimetry. In Aim 3 we will apply the developed imaging method and statistically analyze the relationships between quantitative image measures, dosimetry, dose-response, and therapy outcome. In Aim 4, we consider several potential surrogate radionuclides and assess their utility for pre-therapy dosimetry.

用α-粒子发射器（αRPT）进行放射药物治疗是一种高效的癌症治疗方式。 向癌细胞提供潜在的α粒子辐射 大多数其他癌症疗法。这也是独一无二的，因为α发射器还发出可以成像的照片 核医学方式。这允许患者特定的治疗计划和优化患者 治疗。但是，尚未使用这些αRPT的独特特征，因为αRPP是如此有效 用于治疗患者的活动太低，无法用常规的核医学成像方法成像。在这个 项目我们将开发和实施准确的单光子发射计算机断层扫描（SPECT）成像 克服这一限制的方法。我们的假设是启用定量αRPT成像并使其成为 方便以使其被广泛采用将改善用αRPT治疗的患者的结果。分布 体内radiuclide是估计计划和计划所需的吸收剂量分布的先决条件 优化αRPT。想象患者α发射体的分布存在一些重大挑战。 由于它们的高线性能量转移（LET）和产生的致死性，因此使用低施用活性。典型的 衰减链包括发射照片的多个女儿放射线，也必须确定 他们的活动分布。同样，α发射体的光子发射光谱通常具有许多低丰度 伽玛射线散布在广泛的能量范围内。这些特性使基于成像的剂量法变得困难。 进行的成像尚未定量严格。我们建议开发成像 适用于临床SPECT系统的重建方法，该方法将解释复杂的成像物理学 并允许对αRPT进行验证的定量SPECT成像，以进行准确的剂量计算。总体 目标是将这种定量SPECT成像纳入可以实现的临床实现成像工作流程中 为治疗计划和有效监测提供准确的剂量测定法。我们的小组与 Hopkins创业公司，RadioPharmaceutical Imaging和Dosimetry，LLC（Rapid）的成员已有 已经在αRPT药物的SPECT成像上取得了长足的进步。在AIM1中，我们将把这项工作扩展到 开发定量重建方法，用于对α发射器进行SPECT成像，从而产生准确的 剂量测定的活性分布度量，这也可用于SPECT诊断成像。 成像αRPT的另一个挑战是，患者要求进行多个成像课程以获得 正常器官和肿瘤中所需的药代动力学。在目标2中，我们将调查权衡取舍 在成像时间点的数量和剂量法的准确性之间。在AIM 3中，我们将应用开发的 成像方法和统计分析定量图像测量，剂量测定法之间的关系 剂量反应和治疗结果。在AIM 4中，我们考虑了几种潜在的替代射射线层和 评估其疗程前剂量测定的效用。