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：
8110018
负责人：
LEE JOSEPHSON
金额：
$ 36.15万
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 2014-04-30
项目状态：
已结题

来源：
https://reporter.nih.gov/project-details/8110018
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 Screening procedure 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 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. PUBLIC HEALTH RELEVANCE: Despite the key 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, VF's lack the reactive groups needed for the conjugation of radioactive or magnetic labels and cannot be used with clinical imaging modalities. Our recent advances in fluorochrome chemistry permit the attachment of imaging reporter groups to VF's, and their use for imaging cell death by different imaging modalities. A gadolinium MVF designed for imaging cell death by MRI and an 18F MVF for imaging cell death by PET will be developed and 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害，心脏或大脑中缺血相关损害的程度以及对癌症化疗的反应。尽管细胞死亡在各种病理学中的作用扮演着角色，但目前尚无成像剂可以满足图像这一过程的广泛需求。重要的荧光染色体（VF），细胞死亡研究中的关键试剂，结合死亡，但没有结合活细胞。但是，轻衰减阻止了VF作为荧光探针的临床使用，并且缺乏放射性或磁标记所需的反应性基团。最近，我们合成了一个被称为to-pro 1的市售VF的修改版，并附上了顺磁性gadolinium ion。所得的多模式生命荧光素（MVF）能够通过MRI在体外和体内检测死细胞。 MVF提供了一种基于良好理解的VF行为来成像细胞死亡的广泛方法。此外，通过细胞生物学中的常见研究技术（FACS，显微镜），可以轻松地验证VF在死细胞中的选择性处置。我们将使用不同的物理和光学特性合成MVF，并证明了它们在MRI和PET的各种人类疾病模型（缺血，癌症）中的效用。用于成像MRI成像细胞死亡的Gadolinium MVF和用于对PET成像细胞死亡的18F MVF可以广泛使用的诊断成像中的高度通用工具。公共卫生相关性：尽管细胞死亡在多种病理中起关键作用，但目前尚无成像剂可以满足图像这一过程的广泛需求。重要的荧光染色体（VF），细胞死亡研究中的关键试剂，结合死亡，但没有结合活细胞。但是，VF缺乏放射性或磁标签所需的反应性基团，并且不能与临床成像方式一起使用。我们最近在荧光化学方面取得的进步允许将成像报告基团的附着在VF上，并通过不同的成像方式将其用于成像细胞死亡。将开发用于通过MRI成像细胞死亡的Gadolinium MVF和通过PET对细胞死亡进行成像的18F MVF的成像，并可以广泛使用，在诊断成像中广泛使用，高度一般的工具。