Magnetomotive Optical Molecular Imaging Probes (RMI)

磁动光学分子成像探头 (RMI)

• 批准号: 7271834
• 负责人: Stephen A Boppart
• 金额: $ 37.93万
• 依托单位: UNIVERSITY OF ILLINOIS AT URBANA-CHAMPAIGN
• 依托单位国家: 美国
• 财政年份: 2005
• 资助国家: 美国
• 起止时间: 2005-09-15 至 2009-08-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/7271834
• 关键词: Address; Binding; Biocompatible; Biological Assay; Biomedical Research; Blood Circulation; Breast Cancer Model; Carcinogens; Cells; Characteristics; Chemistry; Class; Clinical; Contrast Media; Dependence; Detection; Development; Diagnosis; Diagnostic Procedure; Diffusion; Disease; Drug Delivery Systems; Drug Kinetics; Engineering; Exhibits; Extravasation; Future; Goals; Growth; Histocompatibility Testing; Image; In Situ; In Vitro; Invasive; Investigation; Magnetic Resonance Imaging; Magnetism; Mechanics; Mediating; Medicine; Methods; Modality; Molecular; Molecular Probes; Monitor; Optical Coherence Tomography; Optics; Penetration; Property; Range; Rattus; Research Personnel; Resolution; Site; Specificity; Speed; Staging; Techniques; Time; Transport Process; Ultrasonic Therapy; Ultrasonography; bioimaging; cancer therapy; desire; drug efficacy; efficacy evaluation; imaging probe; improved; in vivo; iron oxide; magnetic field; millimeter; molecular imaging; multidisciplinary; nanoparticle; nanoscale; neoplastic cell; novel; response; surfactant; tissue phantom; tool; tumor; uptake

DESCRIPTION (provided by applicant): This project will develop a novel class of optical molecular imaging probes that exhibit a magnetomotive response to alter optical contrast when excited by a controllable external magnetic field. Investigational methods for in vivo molecular imaging of targeted magnetomotive probes are demonstrated using optical coherence tomography (OCT). This method will provide a unique resolution scale for the in vivo study and characterization of disease, for high detection sensitivity and dynamic range of induced optical contrast, for the evaluation of the efficacy of targeted drugs, and for basic biomedical research on the pharmacokinetic properties of these magnetomotive molecular probes. This proposal addresses the current need for highly sensitive and specific in vivo molecular imaging that has potential clinical utility. Magnetomotive-OCT (MMOCT), with micron-scale resolution combined with millimeters of penetration, will serve in investigating the dimensional- and surfactant-dependence of probe extravasation and diffusion. Externally-applied magnetomotive forces can be optimized in situ for highly sensitive detection, and can also be used to elucidate the binding strengths and ratios of the probes to their targeted sites. The potential of these probes for contrast in MRI and ultrasonic imaging, and their use in hyperthermic therapy and ultrasound-mediated drug delivery suggests a wide array of future translational investigations with unique capabilities for improving currently available cancer therapies. Specifically, we aim to: 1) Fundamentally understand the magnetomotive contrast of these molecular probes and produce probes optimized for the tissue type and desired information, 2) Develop novel, biocompatible, molecularly-targeted magnetomotive probes with high circulation time, low non-specific uptake, and magnetically-inducible optical contrast, 3) Determine efficacy of probes in targeting tumor cells using in vitro cell assays, and 4) Investigate the delivery mechanisms, extravasation, and specific uptake of targeted agents in vivo in a carcinogen-induced rat mammary tumor model using MMOCT with particular emphasis on tumor uptake at various stages of growth. These aims are synergistic, with the goal of producing optimized magnetomotive molecular probes for a given application (early-stage diagnosis or therapy). Conversely, we expect that the capability afforded by MMOCT to screen for efficacy and specificity will drive further development of more effective probes.

描述（由申请人提供）：该项目将开发一类新型光学分子成像探针，该探针在受可控外部磁场激励时表现出磁动响应以改变光学对比度。使用光学相干断层扫描 (OCT) 演示了靶向磁动势探针体内分子成像的研究方法。该方法将为疾病的体内研究和表征、诱导光学对比度的高检测灵敏度和动态范围、靶向药物的功效评估以及药物代谢动力学特性的基础生物医学研究提供独特的分辨率尺度。这些磁动分子探针。该提案解决了当前对具有潜在临床实用性的高灵敏度和特异性体内分子成像的需求。 磁动力 OCT (MMOCT) 具有微米级分辨率和毫米级穿透力，将用于研究探针外渗和扩散的尺寸和表面活性剂依赖性。外部施加的磁动势可以在原位进行优化，以实现高灵敏度检测，并且还可以用于阐明探针与其目标位点的结合强度和比率。这些探针在 MRI 和超声成像中的对比潜力，以及它们在热疗和超声介导的药物输送中的应用，表明未来的转化研究具有独特的能力，可改善目前可用的癌症疗法。具体来说，我们的目标是：1）从根本上了解这些分子探针的磁动势对比，并生产针对组织类型和所需信息进行优化的探针，2）开发具有高循环时间、低非特异性的新型、生物相容性、分子靶向磁动势探针摄取和磁诱导光学对比，3) 使用体外细胞测定确定探针靶向肿瘤细胞的功效，以及 4) 研究递送机制、外渗和特异性使用 MMOCT 在致癌物诱导的大鼠乳腺肿瘤模型中体内摄取靶向药物，特别强调肿瘤在不同生长阶段的摄取。这些目标是协同作用的，目标是为特定应用（早期诊断或治疗）生产优化的磁动分子探针。相反，我们预计 MMOCT 提供的功效和特异性筛选能力将推动更有效探针的进一步开发。