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

我们发现了一个独特的标志物，入侵胶质瘤细胞产生的PTP切割。 我们开发了一种特异性的分子成像探针，可以与切割的PTP结合。 片段并识别胶质母细胞瘤。因此，我们将测试这一假设， 探针标记高级别的人类神经胶质瘤，并确定侵入的肿瘤边缘。我们将 探索其作为诊断分子成像剂和治疗剂的效用。 原发性脑肿瘤通常起源于中枢神经系统内的支持神经胶质细胞。 神经系统这些肿瘤被称为神经胶质瘤，通常分布广泛 使得手术切除变得不可能侵袭 神经胶质瘤的性质导致难以确定侵袭的程度， 这种疾病几乎无法治愈，平均生存期约为一年。PTP是 细胞表面受体蛋白酪氨酸磷酸酶（RPTP）和细胞粘附 在人类神经胶质瘤中表达下调的分子。最新数据 提示在PTP下调过程中，蛋白质被蛋白水解， 片段仍然与胶质母细胞瘤细胞相关。在这里，我们描述的研究， 利用一种独特的强大的分子成像探针的PTP ²片段，并测试其 在体内的有效性。我们的假设是，探测器将检测到迁移， 在细胞水平上抑制侵袭性胶质母细胞瘤，并最终可用于人类 患者用磁共振成像（MRI）对肿瘤成像。识别 PTP等关键分子靶点的研究将允许开发新的策略， 诊断、成像并最终治疗胶质瘤。据设想，该探测器还可以 在手术过程中用于指导肿瘤的神经外科手术， 以及精确的肿瘤切除，这将提高患者的生存率。 目的1：确定PTP？切割片段与 各种类型和级别的人类胶质瘤的侵袭性。 目的2：评估肽探针在体外监测迁移的胶质瘤细胞中的效用。 脑切片侵袭测定。 目的3：检测探针在体内检测肿瘤和迁移的胶质瘤细胞的效用 在啮齿动物的异位和原位人脑肿瘤模型中。

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.