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Detecting invading glioma cells through in vivo molecular imaging of the cell sur

通过细胞表面的体内分子成像检测入侵的神经胶质瘤细胞

基本信息

批准号：
8449143
负责人：
SUSANN M BRADY-KALNAY
金额：
$ 35.43万
依托单位：
CASE WESTERN RESERVE UNIVERSITY
依托单位国家：
美国
项目类别：
财政年份：
2009
资助国家：
美国
起止时间：
2009-04-01 至 2014-03-31
项目状态：
已结题

来源：
https://reporter.nih.gov/project-details/8449143
关键词：
Adult Affinity Binding Biological Assay Brain Brain Neoplasms Cell Adhesion Molecules Cell Surface Receptors Cells Characteristics Cleaved cell Clinical Collaborations Contrast Media Data Detection Development Diagnosis Diagnostic Disease Down-Regulation Effectiveness Excision Exhibits Fluorescence Glioblastoma Glioma Histocytochemistry Hour Human Image Imaging Techniques Imaging technology Immigration Injection of therapeutic agent Intracranial Neoplasms Invaded Label Lead Life Magnetic Resonance Imaging Measures Modeling Molecular Molecular Target Monitor Neuraxis Neuroglia Neurosurgeon Operative Surgical Procedures Patients Peptides Primary Brain Neoplasms Property Proteins Proteolytic Processing Rodent Sampling Site Slice System Tail Testing Therapeutic Therapeutic Agents Time Tissues Veins cohort glioma cell line human PTPRT protein imaging probe in vivo molecular imaging neoplastic cell neurosurgery novel strategies outcome forecast reconstruction research study tumor

项目摘要

We identified a unique marker of invading glioma cells that arises from PTP¿ cleavage. We developed a specific molecular imaging probe that binds to the cleaved PTP¿ fragment and recognizes glioblastomas. Therefore, we will test the hypothesis that this probe marks high-grade human gliomas and defines the invading tumor margin. We will explore its utility as a diagnostic molecular imaging agent and as a therapeutic. Primary brain tumors commonly arise from supporting glial cells within the central nervous system. These tumors are called gliomas and typically disperse widely throughout the brain making complete surgical resection impossible. The invasive properties of gliomas lead to difficulties in determining the extent of invasion and make this disease virtually incurable with a mean survival of approximately one year. PTP¿ is a cell surface receptor protein tyrosine phosphatase (RPTP) and a cell adhesion molecule whose expression is down-regulated in human gliomas. Very recent data suggests that during PTP¿ down-regulation, the protein is proteolyzed and a small fragment remains associated with the glioblastoma cells. Here we describe studies that utilize a unique robust molecular imaging probe for the PTP¿ fragment and test its effectiveness in vivo. Our hypothesis is that the probe will detect the migrating and invading glioblastomas at the cellular level and can eventually be used in human patients to image the tumors with magnetic resonance imaging (MRI). Identification of key molecular targets such as PTP¿ will allow development of novel strategies to diagnose, image and eventually treat gliomas. It is envisioned that this probe could also be utilized during surgery to guide neurosurgery of the tumors enabling more complete and precise tumor resection, which will enhance patient survival. Aim 1: Determine the extent of association of the cleaved fragment of PTP¿ with invasiveness of human gliomas of various types and grades. Aim 2: Assess the utility of peptide probes to monitor migrating glioma cells in an ex vivo brain slice invasion assay. Aim 3: Examine the utility of the probe to detect tumors and migrating glioma cells in vivo in heterotopic and orthotopic human brain tumor models in rodents.

我们发现了一种独特的入侵胶质瘤细胞的标记物，它是由PTP切割产生的。