Enhancing Liver Cancer Treatment With Image-Guided Magnetic Hyperthermia

通过图像引导磁热疗增强肝癌治疗

• 批准号: 9248297
• 负责人: Robert Ivkov
• 金额: $ 64.81万
• 依托单位: JOHNS HOPKINS UNIVERSITY
• 依托单位国家: 美国
• 财政年份: 2015
• 资助国家: 美国
• 起止时间: 2015-05-01 至 2020-04-30
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/9248297
• 关键词: Address; Affect; Animal Model; Biodistribution; Brain; Cancer Etiology; Cessation of life; Chemosensitization; Clinic; Clinical Treatment; Complement; Data; Deposition; Diagnosis; Diagnostic radiologic examination; Disease; Distal; Dose; Doxorubicin; Effectiveness; Evaluation; Exhibits; Feasibility Studies; Feedback; Finite Element Analysis; Formulation; Gastrointestinal tract structure; Heart; Heating; Histopathology; Hyperthermia; Image; Imagery; Immunohistochemistry; Incidence; Indolent; Inductively Coupled Plasma Mass Spectrometry; Injection of therapeutic agent; Iron; Kidney; Liver; Magnetic Resonance; Magnetic Resonance Imaging; Magnetism; Malignant Neoplasms; Malignant neoplasm of liver; Measurement; Measures; Methodology; Methods; Modality; Modeling; Monitor; Organ; Organ failure; Oryctolagus cuniculus; Palliative Care; Pancreas; Pathway interactions; Patients; Perfusion; Physiology; Primary Malignant Neoplasm of Liver; Primary carcinoma of the liver cells; Procedures; Roentgen Rays; Site; Structure; Symptoms; Technology; Temperature; Testing; Therapeutic; Therapeutic Agents; Therapeutic heat application; Time; Tissues; Toxic effect; Translating; Treatment Efficacy; Tumor Biology; Tumor Tissue; Unresectable; Xenograft procedure; advanced disease; base; cancer cell; cancer therapy; chemotherapeutic agent; chemotherapy; contrast enhanced; contrast imaging; cost effective; image guided; image guided intervention; imaging capabilities; improved; iron oxide; magnetic field; minimally invasive; mortality; mouse model; nanoparticle; new technology; perfusion imaging; public health relevance; response; standard of care; systemic toxicity; targeted delivery; tool; treatment effect; treatment planning; tumor; tumor growth

 DESCRIPTION (provided by applicant): Primary liver cancer is the third most common cause of cancer-related death worldwide. Estimates predict that death from this disease is on the rise because both incidence and mortality are projected to increase. Death usually follows organ failure from progression of local disease. Often patients have already progressed to advanced and unresectable tumors at the time the disease is diagnosed, largely because early stage disease exhibits no symptoms. In such cases, only non-surgical palliative treatment options are available. Image- guided interventions have emerged as potent minimally invasive procedures that offer individualized tumor targeting, with ability to address local disease and minimize systemic toxicities. Yet, these procedures only modestly improve patient survival, creating a need for new technology. The effectiveness of non-ablative heat therapy or hyperthermia (HT) as a complement for other therapies is well-established for unresectable cancers. HT broadly affects tumor biology and it can dramatically affect tumor structure and physiology in ways that enhance the potency of chemotherapeutic agents. The critical barriers to effectively implementing HT for cancer therapy have been targeting the heat to the tumor and delivering the proper heat dose. Magnetic iron oxide nanoparticles (MIONs) offer the capability to overcome these barriers because they provide both heating and imaging capability to enhance targeted delivery of therapy. MIONs produce heat within the tumor when exposed to alternating magnetic fields (AMFs). This heat conducts throughout the tumor to enhance delivery and effectiveness of other therapeutic agents. An image-guided approach offers the potential of real-time visualization of MION distribution with feedback on effective tumor targeting and the necessary information to develop robust treatment planning, creating the potential for individualized therapy. We have recently developed a MION formulation that provides dual imaging (x-ray and magnetic resonance), heating with low- power magnetic fields, and that enables co-formulation with standard chemotherapy agents. This formulation comprises MIONs, embedded in the oily medium of lipiodol. We hypothesize that x-ray image-guided magnetic hyperthermia will sensitize cancer cells to chemotherapy leading to superior efficacy when compared to chemotherapy alone. The effects of therapy, following image-guided delivery of the MION-lipiodol formulation will be assessed in xenograft mouse models of hepatocellular carcinoma. Imaging and image-guided delivery, biodistribution of MIONs, and quantitative measures of MION distribution before and after heating will be assessed in the orthotopic VX2 tumor model in rabbit livers, a preferred animal model for interventional image- guided liver procedures. Successful completion of the proposed project will provide the necessary data and tools to advance this technology closer to clinical treatment of unresectable primary liver cancer.

 描述（由适用提供）：原发性肝癌是全球与癌症相关死亡的第三大原因。据估计，由于预计发病率和死亡率都会增加，该疾病的死亡正在增加。死亡通常是由于局部疾病进展而导致器官失败。在诊断出疾病时，患者通常已经发展为晚期和无法切除的肿瘤，这主要是因为早期疾病没有症状。在这种情况下，仅提供非手术姑息治疗方案。图像引导的干预措施已成为潜在的微创手术，这些程序具有个性化的肿瘤靶向，具有解决局部疾病并最大程度地减少全身毒性的能力。但是，这些程序只会适度改善患者的生存，从而需要新技术。对于无法切除的癌症而言，非燃烧性热疗法或高温（HT）（HT）作为其他疗法的有效性是完善的。 HT广泛影响肿瘤生物学，它可以以增强化学治疗剂效力的方式极大地影响肿瘤的结构和生理。有效实施HT进行癌症治疗的关键障碍将热量靶向肿瘤并提供适当的热剂量。磁氧化铁纳米颗粒（MION）提供了克服这些障碍的能力，因为它们提供了加热和成像能力，以增强靶向的治疗递送。当暴露于替代磁场（AMF）时，Mions在肿瘤内产生热量。这种热量在整个肿瘤中进行，以增强其他治疗剂的递送和有效性。图像指导的方法提供了对MION分布的实时可视化的潜力，并提供了有关有效肿瘤靶向的反馈以及制定可靠治疗计划的必要信息，从而为个性化治疗带来了潜力。我们最近开发了一种MION公式，该公式提供了双成像（X射线和磁共振），使用低功率磁场加热，并可以与标准化学疗法剂进行共制造。该公式包括嵌入lipidol的油性培养基中的MION。我们假设X射线图像引导的磁性高温会感觉到癌细胞接受化学疗法，从而与单独的化学疗法相比，从而提高效率。治疗的作用，在图像引导的分子脂多公式的递送之后，将在肝细胞癌的特征小鼠模型中评估。在兔子生活中，将评估成像和图像引导的输送，MION的生物分布以及加热前后的MION分布的定量测量方法，这是兔子Lives的原位VX2肿瘤模型，这是一种介入图像引导的肝手术的首选动物模型。拟议项目的成功完成将提供必要的数据和工具，以使这项技术更接近不可切除的原发性肝癌的临床治疗。