权益分类	功能权益	普通用户	{{item.name}}会员
{{category.name}}	{{benefitItem.name}}

Imaging and Targeted Auger Radiotherapy of High-Grade Glioma

高级别胶质瘤的成像和靶向俄歇放射治疗

基本信息

批准号：
10559627
负责人：
Joel Richard Garbow
金额：
$ 67.25万
依托单位：
WASHINGTON UNIVERSITY
依托单位国家：
美国
项目类别：
财政年份：
2020
资助国家：
美国
起止时间：
2020-05-01 至 2025-01-31
项目状态：
未结题

来源：
https://reporter.nih.gov/project-details/10559627
关键词：
Affinity Amino Acids Animal Model Applications Grants Area Autoradiography Binding Biological Assay Brain Bromine Cell Nucleus Cells Conformal Radiotherapy DNA Repair DNA Repair Enzymes Development Diagnostic Diffusion Dose Enzymes Excision Exhibits Experimental Models Future Glioblastoma Glioma Goals Image Implant In Vitro Iodine Irradiated tumor Label Lead Magnetic Resonance Imaging Malignant - descriptor Maximum Tolerated Dose Measures Modeling Mus Necrosis Neurosphere Pathology Patients Performance Perfusion Physiology Poly(ADP-ribose) Polymerase Inhibitor Positron Positron-Emission Tomography Primary Brain Neoplasms Prognosis Protocols documentation Publications Publishing Radiation Radiation necrosis Radiation therapy Radioisotopes Radiolabeled Radionuclide therapy Recurrence Recurrent tumor Reporting Research Project Grants Structure Surgically-Created Resection Cavity Targeted Radiotherapy Technology Therapeutic Therapeutic Agents Therapeutic Studies Time Tissues Toxic effect Treatment Efficacy Tumor Volume U251 analog cell killing chemotherapy cytotoxicity design experimental study image guided imaging study improved in vivo inhibitor mouse model neurosurgery new technology non-invasive imaging novel overexpression radioligand research clinical testing response biomarker small molecule inhibitor standard of care theranostics therapeutic biomarker tissue oxygenation treatment effect treatment response tumor uptake

项目摘要

SUMMARY/ABSTRACT Glioblastoma (GBM) is a highly aggressive, malignant, primary brain tumor. Maximal neurosurgical tumor resection, followed by highly conformal radiation and concurrent chemotherapy, remains the standard of care for GBM patients. These tumors inevitably recur. Given the dismal prognosis, improved technologies are desperately needed to enable better treatment of recurrent GBM. An additional complicating factor is the diagnostic challenge of non-invasively discriminating recurrent GBM from radiation necrosis (RN). PARP-1, an enzyme involved in DNA repair, is selectively overexpressed in the nuclei of glioma cells. In recent years, radiolabeled PARP-1 inhibitors have been investigated for the non-invasive imaging of PARP-1 expression in glioma, as well as other tumors. Radiolabeled PARP-1 inhibitors have also been proposed for targeted radiotherapy, though, to date, there have only been two published reports. In this application, we propose to examine existing radiolabeled PARP-1 inhibitors and to synthesize and evaluate novel radiolabeled PARP-1 inhibitors, as theranostic agents for glioblastoma. Radionuclides of iodine and bromine are proposed for imaging and therapeutic studies. Herein, we will focus on positron-emitting radionuclides for PET imaging and Auger- emitting radionuclides for therapy. These studies will be supported by advanced MRI experiments aimed at characterizing the physiology of tumors and RN, and for assessing therapeutic response. The aims of the proposal are to: i) synthesize various established and novel radiolabeled PARP-1 inhibitors, and evaluate their uptake and efficacy in vitro, ii) evaluate radiolabeled PARP-1 inhibitors for uptake in murine models of glioblastoma and experimental radiation necrosis, and iii) determine the therapeutic efficacy of the PARP-1 inhibitors in murine models of glioblastoma. This grant application will be led by a quality team of experts, specializing in models of experimental radiation necrosis and MR imaging (Dr. Joel Garbow); targeted radiation therapy and PET imaging (Dr. Buck Rogers); radioligand development and labeling (Dr. Dong Zhou); in vitro binding assays and autoradiography (Dr. Jinbin Xu); and radiolabeled PARP-1 inhibitors and glioma animal models (Dr. Thomas Reiner). If successful, our approach will provide a new technology driven paradigm for treating patients with recurrent glioblastoma.

摘要/文摘