Hyperpolarized 129Xe MRI for imaging NK cell therapy of lung metastasis

超极化 129Xe MRI 用于肺转移的 NK 细胞治疗成像

基本信息

批准号：
10646013
负责人：
James A Bankson
金额：
$ 18.93万
依托单位：
UNIVERSITY OF TX MD ANDERSON CAN CTR
依托单位国家：
美国
项目类别：
财政年份：
2023
资助国家：
美国
起止时间：
2023-05-01 至 2025-04-30
项目状态：
未结题

来源：
https://reporter.nih.gov/project-details/10646013
关键词：
Address Adoptive Transfer Affect Allogenic Anatomy Animals Antigens Biodistribution Biopsy Cell Culture Techniques Cell Therapy Cells Cellular immunotherapy Chemicals Child Childhood Cancer Treatment Clinic Clinical Development Erythrocytes Excision FDA approved Fluorocarbons Foundations Gases Goals Image Imaging Device Immune Immunotherapy Infusion procedures Inhalation Kinetics Label Logistics Lung Magnetic Resonance Imaging Malignant Neoplasms Metastatic Neoplasm to the Lung Methods Modality Modeling Monitor NK cell therapy Natural Killer Cell Immunotherapy Natural Killer Cells Neoplasm Metastasis Patients Phase I Clinical Trials Physiology Plasma Positron-Emission Tomography Protocols documentation Radiation Radiation Dose Unit Recurrence Refractory Reporting Resolution Respiratory physiology Safety Sensitivity and Specificity Solid Neoplasm Structure of parenchyma of lung T-Lymphocyte Technology Therapeutic Time Tissues Tracer Treatment Failure Validation Visualization Water absorption amphiphilicity anatomic imaging biomedical imaging cancer therapy cellular imaging clinical translation cost cytotoxicity density detection sensitivity electronic cigarette use feasibility testing imaging approach imaging biomarker imaging modality immune imaging improved in vivo innovation insight interest iron oxide nanoparticle lung imaging metabolic imaging migration mortality nanoDroplet non-invasive imaging novel strategies nuclear imaging osteosarcoma pediatric patients respiratory gas respiratory imaging response serial imaging soft tissue success superparamagnetism translatable strategy tumor volunteer

项目摘要

Abstract. Emerging cell-based therapies may greatly improve therapeutic success of cancer treatment. NK cell immunotherapy is particularly important in treatment of pediatric cancers, where information on tumor immunogens is lacking. Recently, there has been increased interest in the use of adoptive transfer of ex-vivo expanded NK cells for the treatment of solid tumors due to their innate features, higher safety compared to T cells and lower cost. This emerging therapy is of particular importance in osteosarcoma where 30-35% of patients die of pulmonary metastases due to a treatment-failure rate of 85% in this patient group. However, an important problem with implementation of cell therapies in the clinic is our inability to readily assess the presence and distribution of therapeutic cells after administration. Visualization of immune cell distribution and migration with non-invasive imaging could offer significant new insight into the progression of immunotherapy between infusion and invasive biopsy or resection. Although there are a number of viable approaches for imaging of immunotherapy, all current strategies have limitations and no technology has been proven as a single solution for longitudinal imaging of cellular immunotherapies. Therefore, it is important to continue pushing the limits of available imaging tools in order to find solutions that would address the pressing clinical needs. Hyperpolarized (HP) 129Xe MRI has recently emerged as a promising modality for direct imaging of respiratory function and gas absorption. Spectral separation between HP 129Xe gas in the airspace, tissue/plasma, and red blood cells permits quantification of gas absorption and exchange. Further, a few exploratory studies have demonstrated that chemical exchange saturation transfer (CEST) of HP 129Xe in perfluorocarbon nanodroplets (PFC NDs) can significantly enhance sensitivity to the presence of PFC ND’s due to a strong chemical shift between 129Xe gas in PFC and water. We see these developments as a tremendous opportunity to develop clinically translatable strategy for imaging NK cell therapy in the lungs. Here we propose to develop foundation for HP 129Xe CEST (hyperCEST) MRI of NK cells in vivo. The secondary goal is identification of imaging biomarkers of functional HP 129Xe MRI that may provide additional insight into response to cell immunotherapy. We will rely on our extensive expertise in (i) synthesis and applications of PFC NDs in biomedical imaging including cell labeling, and (ii) quantitative MRI, multinuclear imaging (13C, 19F, 129Xe) and metabolic imaging. Our hypothesis is that labeling of NK cells with PFC NDs optimized for 129Xe hyperCEST MRI will not adversely affect their functionality and will allow non-invasive NK cell monitoring with high sensitivity and specificity in the lungs. At the completion of these studies we will have a combination of optimized and validated probes for NK cell 129Xe hyperCEST MRI with corresponding imaging protocols that will provide foundation for further development of this promising technology towards clinical translation.

摘要：新兴的基于细胞的疗法可以极大地提高癌症治疗的成功率。免疫疗法在儿科癌症的治疗中尤其重要，其中有关肿瘤的信息最近，人们对体外过继转移的兴趣日益浓厚。扩增的NK细胞由于其先天特性，用于治疗实体瘤，与T细胞相比安全性更高这种新兴疗法对于骨肉瘤尤其重要，骨肉瘤中有 30-35% 的患者患有骨肉瘤。在该患者组中，由于治疗失败而导致的肺转移死亡率为 85%。在临床上实施细胞疗法的问题是我们无法轻松评估细胞疗法的存在和给药后治疗细胞的分布可视化免疫细胞的分布和迁移。非侵入性成像可以为输注之间免疫治疗的进展提供重要的新见解尽管有许多可行的成像方法。免疫疗法，当前所有策略都有局限性，并且没有任何技术被证明可以作为单一解决方案因此，继续突破细胞免疫疗法的极限非常重要。可用的成像工具，以找到解决紧迫的临床需求的解决方案。 (HP) 129Xe MRI 最近已成为一种有前途的呼吸功能和气体直接成像方式空气空间、组织/血浆和红细胞中的 HP 129Xe 气体之间的光谱分离允许吸收。此外，一些探索性研究表明，气体吸收和交换的量化。 HP 129Xe 在全氟化碳纳米液滴 (PFC ND) 中的化学交换饱和转移 (CEST) 可以由于 129Xe 气体之间存在强烈的化学位移，显着提高对 PFC ND 存在的灵敏度我们认为这些进展是开发可临床转化的巨大机会。在此，我们建议为 HP 129Xe CEST 开发基础。 (hyperCEST) 体内 NK 细胞的 MRI 的第二个目标是识别功能性的成像生物标志物。 HP 129Xe MRI 可以为细胞免疫疗法的反应提供更多见解。在 (i) PFC ND 的合成和生物医学成像应用（包括细胞标记）方面拥有丰富的专业知识， (ii) 定量 MRI、多核成像（13C、19F、129Xe）和代谢成像。使用针对 129Xe hyperCEST MRI 优化的 PFC ND 标记 NK 细胞不会对其功能产生不利影响完成后将允许在肺部进行高灵敏度和特异性的非侵入性 NK 细胞监测。在这些研究中，我们将结合优化和验证的 NK 细胞 129Xe hyperCEST MRI 探针相应的成像协议将为这一有前途的进一步发展奠定基础临床转化技术。