Core Research Services for Molecular Imaging and Imaging Sciences

分子成像和成像科学的核心研究服务

• 批准号: 7733649
• 负责人: Bradford Wood
• 金额: $ 5.12万
• 依托单位: CLINICAL CENTER
• 依托单位国家: 美国
• 资助国家: 美国
• 起止时间: 至
• 项目状态: 未结题
• 来源: https://reporter.nih.gov/project-details/7733649
• 关键词: Ablation; Academic Training; Adrenocortical carcinoma; Affinity; Algorithms; Amyloid beta-Protein; Animals; Area; Arterial Fatty Streak; Arts; Atherosclerosis; Avidity; Basic Science; Binding; Biochemical; Biochemistry; Biological Assay; Biology; Biopsy; Boxing; Cancer Detection; Cancer Patient; Characteristics; Chemicals; Chemistry; Clinic; Clinical; Clinical Research; Clinical Services; Clinical Trials; Collaborations; Colonic Polyps; Communication; Communities; Computer Assisted; Computer Simulation; Confocal Microscopy; Contrast Media; Core Facility; Country; Cultured Cells; DNA analysis; Depth; Detection; Development; Devices; Diagnostic radiologic examination; Discipline; Discipline of Nuclear Medicine; Doctor of Philosophy; Dose; Drug Delivery Systems; Drug Kinetics; Electrodes; Electromagnetics; Engineering; Equipment; Event; Feedback; Fibroid Tumor; Fluorescence-Activated Cell Sorting; Focused Ultrasound Therapy; Future; Gene Expression; Genetic Engineering; Genomics; Goals; Health Services Research; Heating; Hereditary Renal Cell Carcinoma; Histocytochemistry; Histopathology; Home environment; Human; Image; Imaging Techniques; Immunocompromised Host; Immunology; In Vitro; Institutes; Integrins; Intervention; Interventional radiology; Intramural Research Program; Kidney Neoplasms; Laboratories; Lasers; Legal patent; Liposomes; Liver Abscess; Liver neoplasms; Localized; Magnetic Resonance Imaging; Magnetism; Mechanics; Medical Device; Metabolic; Methods; Microscopy; Mission; Modality; Molecular; Molecular Biology; Molecular Probes; Molecular Target; Monitor; Monoclonal Antibodies; Multicenter Trials; Multimodal Imaging; Names; Natural History; Navigation System; Needles; Nephrons; North America; Operating Rooms; Optics; Pathologic; Pathology; Pathway interactions; Patient Care; Patients; Performance; Pharmaceutical Preparations; Phase; Phase I Clinical Trials; Phase III Clinical Trials; Phenotype; Pheochromocytoma; Physics; Physiological; Plant Roots; Process; Productivity; Proteomics; Radiology Specialty; Radionuclide Imaging; Receptor Up-Regulation; Research; Research Infrastructure; Research Institute; Research Personnel; Research Training; Resources; Rewards; Safety; Sampling Studies; Science; Scientist; Screening procedure; Serum; Services; Signal Transduction; Site; Stem Cell Development; Synthesis Chemistry; System; Techniques; Technology; Test Result; Testing; Therapeutic; Therapeutic Embolization; Thermal Ablation Therapy; Tissue Sample; Tissues; Training; Training Programs; Translating; Translational Research; Translations; Treatment Protocols; Ultrasonography; United States National Institutes of Health; Work; acute coronary syndrome; base; bench to bedside; bioimaging; cell motility; chemotherapy; clinical application; concept; design; experience; functional genomics; image guided intervention; imaging probe; improved; in vivo; innovation; laser capture microdissection; molecular imaging; molecular pathology; nanoparticle; neuroimaging; new technology; novel; novel diagnostics; optical imaging; peptidomimetics; programs; radiologist; research study; sensor; soft tissue; tissue culture; tool; trafficking; tumor; vector

There is tremendous inherent value of the Radiologist investigators as a core resource for the mission of the Intramural Research Program. The strength of the Radiologist investogators lies in its deep and robust roots and networks to the research of the Institutes, as the Diagnostic Radiology Department (DRD) provides major radiology, imaging, and image guided interventional support for the work of the Institutes. The DRD provides clinical services to the ICs and CC, but also has a modest research agenda and mandate, as well as a small research training program. Thus, DRD research is most often synergistic with the projects and missions of the The core facilities have helped support translation of Computer-aided detection algorithms to the clinic for the detection of colonic polyps as well as new ways to translate navigation technologies to clinic using the multimodality operating room of the future, of which the CC is home to a worlds first suite of its kind. The Clinical Center became a place for the delivery mechanical or thermal energy to the soft tissues via needle electrodes or high intensity focused ultrasound combined with thermally deployed vectors containing chemotherapy agents or contrast for various liver tumors. This latter concept was taken from bench to bedside here at the Clinical Center. Novel ways to improve the technique of thermal ablation have been pioneered here, including the use of RFA for liver abscesses in the immunocompromised, and the use of RFA for nephron sparing kidney tumor ablation in hereditary renal cell carcinoma in patients without other effective means of treatment. Core resources support the study of the natural history, safety, and efficacy of this new technology for novel clinical applications like adrenocortical carcinoma, liver abscess in the immunocompromised host, and for hormonally-active tumors like pheochromocytoma. NIH Clinical Center became the home to one of the first drug + device combination phase 1 clinical trials in heat deployed drug delivery, the result of many years of bench to bedside translation, and is now in 40 centers and 5 countries for Phase 3 trials. The Clinical Center also helped develop a navigation system that uses tiny electromagnetic sensors inside of medical devices that converts the device into a GPS-like localization system, with the device being the car, and the magnetic box field generator sitting nearby being the satellite. The first clinical trial in humans using this technology for tumor ablations was performed here. The multimodality multiparametric navigation system may help clarify the significance of specific tissue phenotyping, proteomics, genomics, or in prescribing the appropriate therapeutic cocktail for the cancer patient. Such targeted sequential biopsies are becoming a routine research tool for many NCI investigators. High intensity focused ultrasound (HIFU) activating thermally sensitive contrast agents or drugs is a relatively new phase of study, with phase 1 dose escalation trials planned. The NIH will also be the home of North Americas first MRI guided Spiral HIFU, and will help direct a multicenter trial at transcatheter fibroid embolization versus MRI-guided HIFU fibroid ablation. NIH has long been the site for the CT-based multimodality procedural suite of the future. The Molecular Imaging Lab became more translational in FY 08, and less based upon mechanistic work, exploratory studies, and basic science. Avb3 integrin antagonist was patented, investigated, as applied to atherosclerosis and tumor imaging and possibly therapeutic delivery with collaborators from NIBIB and NCI. Conceptually, imaging can be used to facilitate target identification, localize the relevant molecular targets in vivo in a spatially and/or temporally resolved fashion, and ultimately personalized treatment regimens can be developed based on a combination of imaging and image guided tissue analysis. In the past few years, molecular imaging has become a popular term. The core efforts support translational goals and first-in-human clinical applications, rather than the primary discovery of specific imaging and therapeutic probes. Molecular imaging may seem like a linear process of building chemical or biologic probes specific to molecular targets identified by molecular biology, pathology and immunology (using techniques such as functional genomics, proteomics, immuno-histochemistry or fluorescence-activated cell sorting (FACS)). These chemical or biologic probes are designed to be detected in vivo by various imaging techniques. Using these probes various biologic processes such as gene expression, molecular receptor up-regulation and metabolic activities can be monitored in vivo (a powerful research tool). Such developments of molecular probes requires the collaboration of scientists from multiple disciplines such as chemistry, computer modeling, biochemistry, molecular biology and drug delivery. Typically, chemical probes can be designed either by a rational approach, sometimes using computer modeling, or drug + device paradigms. The potentially useful chemical probes are then subjected to in vitro biochemical assays followed by in vivo studies. In vivo drug delivery has many hidden barriers on the way to clinical trials in patients. Understanding physiologic barriers and pharmacokinetics is critical issues for translation. For example, the experience from years of immuno-scintigraphy research suggests that even in the ideal case only 0.001 to 0.01% of monoclonal antibodies injected intravenously will reach and bind to target tissues in humans despite high selectivity, affinity and avidity in vitro. Since many of the molecular targets exist only in low concentrations in the target tissues, signal amplification by chemical or physical means may be required (such as image guided HIFU). In order to prove that an imaging probe is effective, image guided tissue biopsies from the animals undergoing the imaging experiments need to be carried out. These tissue samples are studied with techniques such as immuno-histochemistry, histopathology, c-DNA analysis etc. to confirm that the imaging test results correspond to the in vitro tissue analysis results. Once we have an imaging test that can be used for tracking a molecular event in vivo, new opportunities are available. One can imagine using this imaging test to select tissues with a certain molecular characteristics and then use these images for guiding procurement of tissue samples. These tissue samples can then be analyzed using various techniques. This type of approach will allow the study and interactions between different molecular pathways which could result in identifications of molecular targets relationships. New molecular imaging probes developed for the new molecular targets in a highly iterative process. Prior projects assisted by Molecular Imaging Lab staff have included Integrin antagonists for the detection of cancer, vulnerable atherosclerotic plaque, optical probes for beta amyloid, optical biufunctional compounds, targeted contrast agents, polymerized liposomes, peptidomimetic integrin antagonists, serum proteomic screening in acute coronary syndromes, to name a few.

放射科医生研究人员作为校内研究计划使命的核心资源具有巨大的内在价值。放射科医生研究人员的优势在于其对研究所研究的深厚而强大的根基和网络，因为诊断放射科 (DRD) 为研究所的工作提供主要的放射学、成像和图像引导介入支持。 DRD 为 IC 和 CC 提供临床服务，但也有适度的研究议程和任务，以及小型研究培训计划。因此，DRD 研究通常与 DRD 的项目和使命具有协同作用。 核心设施帮助支持将计算机辅助检测算法​​转化为临床以检测结肠息肉，以及使用未来的多模态手术室将导航技术转化为临床的新方法，其中 CC 拥有世界上第一套此类手术室。 临床中心成为通过针电极或高强度聚焦超声结合包含化疗药物或各种肝脏肿瘤造影剂的热部署载体向软组织输送机械能或热能的地方。后一个概念在临床中心从实验室带到了床边。这里开创了改进热消融技术的新方法，包括使用 RFA 治疗免疫功能低下的肝脓肿，以及使用 RFA 对没有其他有效治疗手段的遗传性肾细胞癌患者进行保留肾单位的肾肿瘤消融。核心资源支持这项新技术的自然史、安全性和有效性研究，用于新的临床应用，如肾上腺皮质癌、免疫功能低下宿主的肝脓肿，以及嗜铬细胞瘤等激素活性肿瘤。 NIH 临床中心成为第一个热部署药物输送药物+设备组合 1 期临床试验的所在地，这是多年实验室到床边转化的结果，目前已在 40 个中心和 5 个国家进行 3 期试验。临床中心还帮助开发了一种导航系统，该系统使用医疗设备内部的微型电磁传感器，将该设备转换为类似 GPS 的定位系统，该设备是汽车，而位于附近的磁场发生器是卫星。首次使用该技术进行肿瘤消融的人体临床试验就是在这里进行的。多模态多参数导航系统可能有助于阐明特定组织表型、蛋白质组学、基因组学的重要性，或有助于为癌症患者开出适当的治疗鸡尾酒。这种有针对性的连续活检正在成为许多 NCI 研究人员的常规研究工具。高强度聚焦超声 (HIFU) 激活热敏造影剂或药物是一个相对较新的研究阶段，计划进行一期剂量递增试验。 NIH 还将成为北美首个 MRI 引导螺旋 HIFU 的所在地，并将帮助指导经导管肌瘤栓塞与 MRI 引导 HIFU 肌瘤消融的多中心试验。 NIH 长期以来一直是未来基于 CT 的多模态程序套件的所在地。 分子成像实验室在 08 财年变得更加转化，不再依赖机械工作、探索性研究和基础科学。 Avb3 整合素拮抗剂已获得专利并进行了研究，应用于动脉粥样硬化和肿瘤成像，并可能与 NIBIB 和 NCI 的合作者进行治疗交付。从概念上讲，成像可用于促进靶标识别，以空间和/或时间解析的方式定位体内相关分子靶标，并最终可基于成像和图像引导组织分析的组合开发个性化治疗方案。在过去的几年里，分子成像已经成为一个流行的术语。核心工作支持转化目标和首次人体临床应用，而不是特定成像和治疗探针的主要发现。分子成像似乎是构建针对分子生物学、病理学和免疫学（使用功能基因组学、蛋白质组学、免疫组织化学或荧光激活细胞分选 (FACS) 等技术）识别的分子靶标的化学或生物探针的线​​性过程。 这些化学或生物探针被设计为通过各种成像技术进行体内检测。 使用这些探针可以在体内监测各种生物过程，例如基因表达、分子受体上调和代谢活动（强大的研究工具）。 分子探针的这种发展需要化学、计算机建模、生物化学、分子生物学和药物输送等多个学科的科学家的合作。 通常，化学探针可以通过合理的方法（有时使用计算机建模）或药物+设备范例来设计。 然后对潜在有用的化学探针进行体外生化测定，然后进行体内研究。体内药物递送在患者临床试验的道路上存在许多隐藏的障碍。 了解生理障碍和药代动力学是翻译的关键问题。 例如，多年免疫闪烁扫描研究的经验表明，即使在理想情况下，尽管体外具有高选择性、亲和力和亲合力，静脉注射的单克隆抗体也只有 0.001% 至 0.01% 能够到达并结合到人体靶组织。 由于许多分子靶标仅以低浓度存在于靶组织中，因此可能需要通过化学或物理手段放大信号（例如图像引导 HIFU）。 为了证明成像探针的有效性，需要对接受成像实验的动物进行图像引导的组织活检。 这些组织样本通过免疫组织化学、组织病理学、c-DNA分析等技术进行研究，以确认成像测试结果与体外组织分析结果相对应。 一旦我们有了可用于跟踪体内分子事件的成像测试，就会出现新的机会。 可以想象使用这种成像测试来选择具有某种分子特征的组织，然后使用这些图像来指导组织样本的获取。 然后可以使用各种技术分析这些组织样本。 这种类型的方法将允许研究不同分子途径之间的相互作用，从而识别分子靶标关系。 在高度迭代的过程中为新分子靶标开发新的分子成像探针。 分子成像实验室工作人员之前协助的项目包括用于检测癌症的整合素拮抗剂、易损动脉粥样硬化斑块、β淀粉样蛋白的光学探针、光学双功能化合物、靶向造影剂、聚合脂质体、拟肽整合素拮抗剂、急性冠状动脉综合征的血清蛋白质组学筛查等。