A high sensitivity gamma camera using a combination of Compton reconstruction and source proximity for in-vivo imaging of Ac-225

结合康普顿重建和源邻近技术的高灵敏度伽玛相机，用于 Ac-225 体内成像

• 批准号: 10704759
• 负责人: Javier Caravaca Rodriguez
• 金额: $ 79.2万
• 依托单位: UNIVERSITY OF CALIFORNIA, SAN FRANCISCO
• 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/10704759
• 关键词: Acceleration; Acute Myelocytic Leukemia; Adoption; Algorithms; Alpha Particles; Animals; Attention; Beta Particle; Biodistribution; CdZnTe; Cells; Clinical; Collection; DNA; Daughter; Dedications; Deposition; Detection; Development; Devices; Disease; Dose; Drug Kinetics; Event; Gamma Cameras; Gamma Rays; Goals; Head; Hour; Human; Hybrids; Image; Imaging Device; Imaging Techniques; Isotope Therapy; Isotopes; Lesion; Linear Energy Transfer; Location; Malignant Neoplasms; Malignant neoplasm of pancreas; Malignant neoplasm of prostate; Medical; Medical Imaging; Modality; Motivation; Mus; Organ; Outcome; Patients; Pharmaceutical Preparations; Pharmacologic Substance; Property; Radiation therapy; Radioactive; Radioisotopes; Radiopharmaceuticals; Resolution; Safety; Signal Transduction; Solid; Source; Specific qualifier value; Specificity; System; Techniques; Technology; Thick; Time; Tissues; Toxic effect; Translating; Treatment Efficacy; absorption; animal imaging; cancer radiation therapy; cancer therapy; carcinogenicity; castration resistant prostate cancer; clinical application; design; detection sensitivity; detector; imaging capabilities; imaging system; improved; in vivo; in vivo imaging; interest; millimeter; multimodality; novel; performance tests; pre-clinical; preclinical study; prevent; prototype; quantitative imaging; reconstruction; response; simulation; single photon emission computed tomography; success

Project Summary (Abstract) We propose to build a novel gamma imaging device based on the combination of Compton and proximity reconstructions in order to achieve unprecedented sensitivities that will enable in vivo imaging of biodistributions of 225Ac, a promising Targeted Alpha Therapy (TAT) isotope. TAT has demonstrated a remarkable efficacy and specificity for cancer radiotherapy. This is due to the high linear energy transfer and the short free path of alpha particles that result in a higher and more localized energy deposition than that of beta particles. 225Ac is a very promising alpha-emitter that has successfully shown excellent results on the treatment of a number of malignancies, namely, metastatic castration-resistant prostate cancer, pancreatic cancer and acute myeloid leukemia. A key aspect of TAT is the targeting radiopharmaceutical that transports the 225Ac to the carcinogenic cells, preventing free isotopes from delivering a highly toxic radioactive dose to healthy tissue. However, development of novel radiopharmaceuticals is currently limited by the inability of commercial imaging systems to detect 225Ac in vivo. As a result, their pharmacokinetics cannot be fully understood in clinical applications, delaying their FDA approval and hindering the wide adoption of TAT. 225Ac and its daughters can be imaged through the detection of the gamma rays emitted in their decay chain, but the main challenge of this technique (and the reason why current gamma ray imaging systems are not suitable for this task) is that the gamma ray emission activity is extremely low due to the very small doses injected in human patients (0.1MBq/kg) and in preclinical studies (1MBq/kg in mice) to prevent a morbid toxicity. In this scenario, an apparatus with a high gamma ray detection sensitivity is necessary in order to provide images with exposures no longer than a few minutes. We plan to achieve this unprecedented sensitivity by designing a dedicated gamma camera that integrates Compton and proximity imaging in a multi-modality system. These techniques have been successfully in medical imaging applications, but they have never been combined in the same device in order to improve sensitivity and image quality at the same time. To achieve this goal, we propose to quantitatively image Ac-225 in vivo the first time with a Cadmium Zinc Telluride dual-head camera that enables both Compton and proximity imaging. To reach this goal we plan to 1) assemble Compton and proximity gamma camera; 2) develop a multi- modality reconstruction algorithm for Compton and proximity imaging; 3) demonstrate in vivo imaging of 225Ac with the final prototype and perform first in vivo pharmacokinetics study of two 225Ac radiopharmaceuticals, providing a proof of principle in pre-clinical conditions using phantoms and mice. The outcome from this project will be a prototype gamma camera able to image distributions of 225Ac TAT radiopharmaceuticals in-vivo (and potentially other TAT isotopes), and thus, enabling the complete study of their pharmacokinetics to accelerate their development. With our system, we expect to increase the understanding and confidence in TAT.

项目摘要（摘要） 我们提出建立一种基于康普顿和邻近度相结合的新型伽马成像装置 重建，以实现前所未有的灵敏度，这将使生物分布的体内成像 225 Ac是一种有前途的靶向α治疗（达特）同位素。达特已显示出显著的疗效， 对癌症放疗的特异性。这是由于高的线性能量转移和α的短自由程 比β粒子导致更高和更局部化的能量沉积的粒子。225 AC是一个非常 有前途的α-发射体，已成功地显示出良好的结果，对治疗的一些 恶性肿瘤，即转移性去势抵抗性前列腺癌、胰腺癌和急性骨髓性白血病 白血病达特的一个关键方面是靶向放射性药物，其将225 Ac转运至致癌物质。 细胞，防止游离同位素将高毒性放射性剂量传递到健康组织。然而，在这方面， 新型放射性药物的开发目前受到商业成像系统 在体内检测225 Ac。因此，在临床应用中不能完全理解它们的药代动力学， 拖延了FDA的批准，阻碍了达特的广泛采用。225 Ac及其子体可以成像 通过探测衰变链中释放的伽马射线，但这项技术的主要挑战是 (and当前的伽马射线成像系统不适合于该任务的原因）是伽马射线 由于在人类患者中注射的剂量非常小（0.1MBq/kg）， 临床前研究（1 MBq/kg小鼠），以防止病态毒性。在这种情况下，具有高的 伽马射线检测灵敏度是必需的，以便提供曝光不长于几个 分钟我们计划通过设计专用伽马相机来实现这种前所未有的灵敏度， 在多模态系统中集成了康普顿和邻近成像。这些技术已经成功地 但它们从未组合在同一设备中，以提高 图像质量和灵敏度同时提高。为了实现这一目标，我们建议定量成像Ac-225 在体内首次使用碲锌镉双头摄像头， 显像为了实现这一目标，我们计划1）组装康普顿和邻近伽马相机; 2）开发一个多- 用于康普顿和邻近成像的模态重建算法; 3）展示225 Ac的体内成像 使用最终原型并对两种225 Ac放射性药物进行首次体内药代动力学研究， 提供了使用模型和小鼠在临床前条件下的原理证明。这个项目的成果 将是一个原型伽马相机能够图像分布的225 Ac达特放射性药物在体内（和 潜在的其他达特同位素），从而使其药代动力学的完整研究能够加速 他们的发展。通过我们的系统，我们希望增加对达特的理解和信心。