Alpha-emitter Imaging for Dosimetry and Treatment Planning

带α粒子发射器的放射药物治疗(αRPT)是一种高效的癌症治疗方式；它 向癌细胞传递强大的阿尔法粒子辐射，因此不容易产生耐药性 大多数其他癌症疗法。它的独特之处还在于，阿尔法发射器也发射光子，这些光子可以通过 核医学模式。这样就可以制定针对患者的治疗计划并优化患者 心理治疗。然而，αRPT的这些独特功能尚未被使用，因为αRPT是如此有效，以至于 用于治疗患者的活性太低，无法用传统的核医学成像方法进行成像。在这 我们将开发和实施精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 方便，广泛采用，将改善αRPT治疗患者的预后。分布情况 放射性核素在体内的分布是估计计划和 优化αRPT。对患者体内α发射体的分布进行成像有几个重大挑战。 由于它们的高线性能量转移(LET)和由此产生的致命性，使用了低剂量的活动。典型 衰变链包括多个发射光子的子体放射性核素，重要的是还要确定 它们的活动分布。此外，α发射体的光子发射光谱通常具有许多低丰度 伽马射线分布在很大的能量范围内。这些特性使得基于成像的剂量测量变得困难； 已经进行的成像在数量上并不严格。我们建议开发成像技术 适用于临床SPECT系统的重建方法将考虑复杂的成像物理 并允许对αRPT进行经过验证的定量SPECT成像，以进行准确的剂量计算。整体而言 目标是将这种定量SPECT成像纳入临床可实施的成像工作流程中，该工作流程可以 为治疗计划和疗效监测提供准确的剂量学。我们的团队，与 霍普金斯创业公司放射性药物成像和剂量测定有限责任公司(Rapid)的成员 在α显像剂的SPECT成像方面已经取得了长足的进展。在Aim1中，我们将把这项工作扩展到 开发用于α发射体SPECT成像的定量重建方法，以产生准确的 用于剂量测定的活度分布的测量，通常对SPECT诊断成像也是有用的。 αRPT成像的另一个挑战是要求患者返回多次成像会话以获得 正常器官和肿瘤所需的药代动力学。因此，在目标2中，我们将研究权衡 成像时间点数目与剂量测量精度之间的关系。在目标3中，我们将应用开发的 成像方法，并统计分析定量图像测量、剂量学、 剂量反应和治疗结果。在目标4中，我们考虑了几种潜在的替代放射性核素和 评估它们在治疗前剂量测定中的作用。

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.