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

• 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
• 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

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.

抽象的。新兴细胞的疗法可能会大大改善癌症治疗的热成功。 NK细胞 免疫疗法在治疗小儿癌的治疗中尤其重要 缺乏免疫力。最近，人们对使用自适应转移的兴趣增加了 扩展的NK细胞因其先天特征而治疗实体瘤，与T相比，安全性更高 细胞和较低的成本。这种新兴疗法在骨肉瘤中尤其重要，其中30-35％ 该患者组的治疗率为85％，导致肺转移死亡。但是，这是一个重要的 在诊所实施细胞疗法的问题是我们无法轻松评估存在和 给药后治疗细胞的分布。通过可视化免疫物分布和迁移 非侵入性成像可以为输注之间的免疫疗法的进展提供重大的新见解 和侵入性活检或切除。尽管有许多可行的成像方法 免疫疗法，所有当前策略都有局限性，没有任何技术被证明是单一解决方案 用于细胞免疫疗法的纵向成像。因此，重要的是要继续推动限制 可用的成像工具以找到可以满足紧迫临床需求的解决方案。超极化 （HP）129XE MRI最近已成为直接成像呼吸功能和气体成像的希望形态 抽象。空体，组织/血浆和红细胞中HP 129XE气体之间的光谱分离允许 气体抽象和交换的定量。此外，一些探索性研究表明 HP 129XE的化学交换饱和转移（CEST）在全氟碳纳米光（PFC NDS）中可以 由于129xE气体之间的强大化学位移，显着提高了对PFC和PFC的敏感性 在PFC和水中。我们认为这些发展是发展临床翻译的巨大机会 在肺中成像NK细胞疗法的策略。在这里，我们建议为HP 129XE CEST奠定基础 （HyperCest）NK细胞在体内的MRI。第二个目标是识别功能的成像生物标志物 HP 129XE MRI可能会提供对细胞免疫疗法反应的更多见解。我们将依靠我们的 PFC ND在生物医学成像中的合成和应用中的广泛专业知识，包括细胞标记， （ii）定量MRI，多核成像（13C，19F，129XE）和代谢成像。我们的假设是 用针对129XE HyperCest MRI优化的PFC NDS将NK细胞的标记不会对其功能产生不利影响 并将允许在肺中具有高灵敏度和特异性的非侵入性NK细胞监测。完成 在这些研究中，我们将结合NK细胞129XERPERCEST MRI的优化和验证问题 具有相应的成像协议，将为进一步发展这一诺言提供基础 临床翻译的技术。