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Multimodal Vital Fluorochromes for Imaging

用于成像的多模式重要荧光染料

基本信息

批准号：
8461155
负责人：
LEE JOSEPHSON
金额：
$ 35.97万
依托单位：
MASSACHUSETTS GENERAL HOSPITAL
依托单位国家：
美国
项目类别：
财政年份：
2010
资助国家：
美国
起止时间：
2010-07-15 至 2014-07-30
项目状态：
已结题

来源：
https://reporter.nih.gov/project-details/8461155
关键词：
A Mouse A549 Affinity Albumins Animal Model Apoptosis Apoptotic Behavior Binding Biological Assay Biological Markers Blood Brain Camptothecin Cell Death Cell physiology Cells Cellular Stress Cellular biology Chemistry Chemotherapy-Oncologic Procedure Clinical Clinical Trials DNA DNA Binding Detection Diagnostic Imaging Dyes Fluorescein-5-isothiocyanate Fluorescence Fluorescent Probes Fluorochrome Gadolinium Heart Human Pathology Image Immune In Vitro Ions Ischemia Jurkat Cells Kidney Label Life Light Limb structure Liver Magnetic Resonance Imaging Magnetism Malignant Neoplasms Mediating Microscopy Mitochondria Modeling Molecular Target Mus Myocardium Necrosis Optics Organ Transplantation Pathology Pharmaceutical Preparations Play Positron Positron-Emission Tomography Property Radiation therapy Radioactive Rattus Reagent Relaxation Reperfusion Injury Reporter Research Research Technics Role Time Tissues annexin A5 attenuation base caspase-3 chemotherapy design gadolinium oxide human disease image processing imaging modality in vivo meetings mouse model novel strategies physical property public health relevance response screening tool tumor uptake

项目摘要

DESCRIPTION (provided by applicant): Diverse types of probes have been employed to image cell death, in order to determine the immune mediated damage of transplanted organs, the extent of ischemia related damage in the heart or brain, and the response to cancer chemotherapy. Despite the role cell death plays in diverse pathologies, there currently is no imaging agent that meets the widespread need to image this process. Vital fluorochromes (VF's), key reagents in cell death research, bind dead but not live cells. However, light attenuation blocks the clinical use of VF's as fluorescent probes, and they lack the reactive groups needed for the conjugation of radioactive or magnetic labels. Recently, we synthesized a modified version of a commercially available VF known as TO-PRO 1 and attached a paramagnetic gadolinium ion. The resulting multimodal vital fluorochrome (MVF) was able to detect dead cells in vitro and in vivo by MRI. MVF's provide a broad approach to imaging cell death based on well-understood VF behavior. In addition the selective disposition of VF's in dead cells can be easily verified by common research techniques in cell biology (FACS, microscopy). We shall synthesize MVF's with different physical and optical properties, and demonstrate their utility in diverse models of human diseases (ischemia, cancer) by MRI and PET. A gadolinium MVF designed for imaging cell death by MRI and an 18F MVF for imaging cell death by PET can become widely used, highly general tools in diagnostic imaging.

描述（由申请人提供）：为了确定移植器官的免疫介导的损伤、心脏或脑中缺血相关损伤的程度以及对癌症化疗的反应，已经采用了不同类型的探针来对细胞死亡进行成像。尽管细胞死亡在不同的病理学中起作用，但目前还没有成像剂满足对该过程进行成像的广泛需求。细胞死亡研究中的关键试剂--活性荧光染料（VF's）结合死细胞而非活细胞。然而，光衰减阻碍了VF作为荧光探针的临床应用，并且它们缺乏缀合放射性或磁性标记所需的反应基团。最近，我们合成了一种市售VF的修改版本，称为TO-PRO 1，并连接了顺磁性钆离子。由此产生的多模态活体荧光染料（MVF）能够通过MRI在体外和体内检测死细胞。MVF提供了一种广泛的方法来成像细胞死亡的基础上充分理解VF行为。此外，VF在死细胞中的选择性处置可以通过细胞生物学中的常用研究技术（FACS、显微镜）容易地验证。我们将合成具有不同物理和光学性质的MVF，并通过MRI和PET证明它们在人类疾病（缺血，癌症）的不同模型中的实用性。设计用于通过MRI对细胞死亡进行成像的钆MVF和用于通过PET对细胞死亡进行成像的18F MVF可以成为诊断成像中广泛使用的高度通用的工具。