Monodispersed Biocompatible Magnetic Nanoprobes for Improved Diagnostic Imaging

用于改进诊断成像的单分散生物相容性磁性纳米探针

• 批准号: 8123812
• 负责人: Kannan Manjapra Krishnan
• 金额: $ 22.03万
• 依托单位: LODESPIN LABS, LLC
• 依托单位国家: 美国
• 财政年份: 2011
• 资助国家: 美国
• 起止时间: 2011-08-04 至 2013-07-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/8123812
• 关键词: Algorithms; Animal Model; Automobile Driving; Biocompatible; Body Image; Cells; Cessation of life; Complement; Contrast Media; Development; Diagnostic Imaging; Disease; Disorder by Site; Drug Formulations; Early Diagnosis; Effectiveness; Frequencies; Future; Goals; Head Start Program; Home environment; Image; Imaging Techniques; Imaging technology; In Vitro; Location; Magnetic Resonance Imaging; Magnetism; Malignant Neoplasms; Marketing; Medical; Medical Imaging; Molecular Probes; Names; National Cancer Institute; Noise; Nuclear; Patients; Performance; Phase; Plague; Positioning Attribute; Positron-Emission Tomography; Protocols documentation; Protons; Radiation; Radio; Reaction; Relaxation; Resolution; Roentgen Rays; Screening for cancer; Signal Transduction; Site; Staging; Surface; System; Techniques; Technology; Therapeutic; Time; Tissues; Tracer; Tumor Tissue; United States; Work; base; cancer cell; cancer diagnosis; commercialization; disease diagnosis; fight against; imaging modality; improved; in vivo; magnetite ferrosoferric oxide; meter; nanometer; nanoparticle; nanoprobe; nanoscale; neoplastic cell; particle; pre-clinical; scale up; success; tumor; tumor growth

DESCRIPTION (provided by applicant): Magnetic Resonance Imaging (MRI) is an attractive platform for medical imaging because it uses neither harmful radiation nor expensive radio-tracers; however, MRI, even with the aid of suitable contrast agents, is plagued by background noise from the host tissue and lacks the ability to quantify exactly how much contrast agent is present at a given location. Despite the fact that contrast agents are useful in imaging and differentiating abnormal tissues (tumors) from healthy tissues at much larger scales, early detection of a few-thousand cancer cells is difficult due to the lack of contrast differentiating the tumor from surrounding healthy tissue. Additionally, quantification of cells at the disease site is crucial for development of more site-specific contrast agents that will enable future developments in image-guided therapeutics. Thus, there is a critical need to develop magnetic molecular probes that, unlike contrast agents, can be directly imaged, irrespective of the surrounding tissue, and can be simultaneously targeted to disease sites for early diagnostic imaging. Our goal is to use Magnetic Particle Imaging (MPI), a new medical imaging technology recently introduced by Philips that uses the magnetic relaxation of magnetite nanoparticles in alternating fields, to produce three-dimensional images of the distribution of the nanoparticles in the tissue. The magnetic nanoparticles will have a million times more signal in MPI compared to the nuclear paramagnetism of protons used in MRI. Royal Philips and Bruker Biospin, have jointly announced the development of a preclinical MPI hardware and imaging system, to be marketed in 2011/12. However, commercially available magnetite formulations are grossly inadequate for MPI, both in terms of signal intensity and spatial resolution. In fact, if this critical component, i.e. appropriate magnetite nanoparticle-based molecular probes, that are biocompatible and surface functionalized for facile bioconjugation, and tailored for optimal, performance, are not developed now the enormous potential of MPI may never be realized. Based on our knowhow, we propose to develop the technology of the molecular probes crucially required for the success of MPI in a most timely manner. Our three specific aims (SA) will focus on (SA1) development of monodispersed and biocompatible magnetic nanoparticles (MNPs) as molecular probes optimized for any specific driving frequency used in MPI, (SA2) functionalize the MNPs for specific targeting to tumor cells and the surrounding vasculature and determine the targeting effectiveness in vitro, and (SA3) demonstrate MPI's ability to detect and quantify our targeted MNPs in vitro using a home-built magnetic spectrometer, thereby setting the stage for Phase II work involving in vivo imaging and quantification. PUBLIC HEALTH RELEVANCE: Medical imaging, in its many forms, is a crucial technique used by clinicians for diagnosing diseases and determining the correct treatment options for patients. Diagnosis of cancer, a disease that has resulted in over 550,000 deaths in the United States in 2010 alone (National Cancer Institute; www.cancer.gov), is especially difficult and often detected at much later stages when patient survival chances are low. For early detection of a few-thousand cells, it is important to use nanometer-scale probes (1 nanometer = 1 billionth of a meter) that can specifically target cancer cells and be directly imaged, without any interference or noise from the patient's body. In this project, we will develop functionalized magnetic nanoparticle-based molecular probes, with a million times more signal than nuclear paramagnetism used in MRI, for early detection of cancer using a new and emerging technique called Magnetic Particle Imaging (MPI). Our technology will complement the hardware being developed by Philips, the inventors of MPI. This technology, if successful, will be superior to current imaging techniques such as Magnetic Resonance Imaging (MRI) and has the potential to enable early diagnosis, giving patients a head start in the fight against cancer.

描述（由申请人提供）：磁共振成像（MRI）是医学成像的有吸引力的平台，因为它既不使用有害的辐射也不使用昂贵的放射线跟踪器；但是，即使借助合适的对比剂，MRI也会受到宿主组织的背景噪声的困扰，并且缺乏能够准确量化给定位置的对比度的能力。尽管对比剂在更大范围内与健康组织的成像和区分异常组织（肿瘤）有用，但由于缺乏对比度将肿瘤与周围的健康组织区分开来，因此很难早日检测到数千个癌细胞。另外，对疾病部位的细胞进行定量对于开发更特异性的对比剂至关重要，这些对比剂将在图像引导的治疗剂中实现未来的发展。因此，迫切需要开发磁分子探针，与对比剂不同，可以直接成像，而与周围的组织无关，并且可以同时针对疾病部位以进行早期诊断成像。 我们的目标是使用磁性粒子成像（MPI），这是飞利浦最近引入的一种新的医学成像技术，该技术使用磁铁矿纳米颗粒在交替场中的磁性松弛，以产生组织中纳米颗粒分布的三维图像。与MRI中使用的质子的核磁磁性相比，MPI的磁性纳米颗粒的信号将增加一百万倍。 Philips和Bruker Biospin共同宣布开发临床前MPI硬件和成像系统，该系统将于2011/12年销售。但是，在信号强度和空间分辨率方面，MPI的市售磁铁矿制剂严重不足。实际上，如果这种关键成分（即基于合适的磁铁矿纳米粒子探测器）具有生物相容性和表面功能化，以供易于生物缀合，并且为最佳，性能而定制，现在并未开发出MPI的巨大潜力。基于我们的知识，我们建议开发MPI成功最及时的成功所需的分子探针的技术。 我们的三个特定目标（SA）将集中于（SA1）单分散和生物相容性的磁性纳米颗粒（MNP）的开发，作为针对MPI中使用的任何特定驱动频率优化的分子探针（SA2）功能化MNPS，以对肿瘤细胞以及量源的量化和（SA3）的特定靶向靶向，并确定Quancie and vortie and ofter and Procienting我们的量化能力和（SA3），（SA3）的效率（SA3），（SA3）的能力（SA3），MNPS（SA3）的能力（SA3）。使用自制的磁光谱仪在体外进行MNP，从而为涉及体内成像和定量的II期工作奠定了基础。 公共卫生相关性：医学成像以多种形式是临床医生用于诊断疾病并确定患者正确治疗方案的至关重要技术。仅在2010年，美国的疾病诊断为一种疾病，该疾病在2010年在美国（国家癌症研究所； www.cancer.gov）诊断特别困难，并且在患者生存机会较低时通常在更晚的阶段被发现。为了尽早检测几千个细胞，重要的是使用纳米尺度探针（1纳米= 10亿米，可以专门针对癌细胞并直接成像，而不会受到患者身体的任何干扰或噪声。在该项目中，我们将使用MRI中使用的核磁磁性的信号高100万倍，用于使用一种新的和新兴的技术（称为磁性粒子成像（MPI）），其信号高100万倍。我们的技术将补充MPI发明者飞利浦正在开发的硬件。如果成功的话，这项技术将优于当前的成像技术，例如磁共振成像（MRI），并且有可能早期诊断，从而使患者在抗癌斗争方面起步。