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

Injectable reporters to image tumors and guide resection

可注射报告基因对肿瘤进行成像并指导切除

基本信息

批准号：
8705898
负责人：
ROGER Y TSIEN
金额：
$ 62.09万
依托单位：
UNIVERSITY OF CALIFORNIA, SAN DIEGO
依托单位国家：
美国
项目类别：
财政年份：
2011
资助国家：
美国
起止时间：
2011-09-16 至 2016-07-31
项目状态：
已结题

来源：
https://reporter.nih.gov/project-details/8705898
关键词：
Adhesives Adjuvant Therapy Aminolevulinate Animals Antibodies Avidity Beds Biochemical Bioluminescence Blood Vessels Caliber Cell Count Cell Line Cells Cleaved cell Clinical Contrast Media Dendrimers Detection Development Diagnostic Neoplasm Staging Early Diagnosis Ensure Equilibrium Evaluation Excision Firefly Luciferases Fluorescence Gadolinium Gelatinase A Genetic Goals Gold Histology Image Imaging Techniques Immunoglobulin Fragments Implant Indolent Injectable Integrins Label Light Literature Luciferases Magnetic Resonance Imaging Malignant - descriptor Malignant Neoplasms Matrix Metalloproteinases Measurement Measures Membrane Molecular Monitor Monitoring for Recurrence Mus Normal tissue morphology Operative Surgical Procedures Organ Outcome Peptide Hydrolases Peptides Performance Photochemotherapy Positron-Emission Tomography Postoperative Period Preparation Primary Neoplasm Procedures Proteins ROC Curve Receiver Operating Characteristics Recurrence Reporter Residual Tumors Resolution Signal Transduction Solid Neoplasm Specificity Staging Surgeon Techniques Testing Thymidine Kinase TimeLine Tumor stage Variant Viral Weight aqueous fluorophore gadolinium oxide imaging modality improved interest killings link protein molecular imaging mouse model nanoparticle neoplastic cell novel red fluorescent protein response success tumor tumor specificity whole body imaging

项目摘要

Project Summary Early detection with clinically translatable molecular imaging agents: Novel clinically translatable molecular imaging contrast agents for detecting tumors by T1-weighted magnetic resonance imaging (MRI) or positron emission tomography (PET) will be developed, optimized, and quantitatively characterized. The MRI agents are activatable cell penetrating peptides (ACPPs) conjugated to dendrimers bearing gadolinium chelates. The ACPPs' selectivity for matrix metalloproteinases and the stability of the gadolinium chelates will be optimized. The PET reporters will be reduced-size antibodies bearing novel near-infrared (NIR) fluorophores incorporating 18F-fluoborates. Both MRI and PET agents will be tested in mice on tumors stably expressing genetic reporters for fluorescence (FL), bioluminescence (BL), and positron emission tomography (PET), combining best available versions of far-red fluorescent protein, firefly luciferase, and thymidine kinase, expressed as separate but genetically linked proteins separated by self-cleaving viral 2A sequences. These tests will quantify how reliably can such injectable agents detect solid tumors of different sizes and stages of progression, under what circumstances false positive and negative signals are obtained, when is either combination of probe and imaging modality superior to the other, and whether indolent vs. highly malignant and invasive tumors can be distinguished. Evaluation and improvement of FL-guided surgical resection and adjuvant therapies: Intraoperative FL guidance from injectable agents such as ACPPs conjugated to fluorescent dendrimers, reduced-size antibodies labeled with NIR fluorophores, or 5-aminolevulinate will be compared with FL guidance from the fluorescent protein representing perfect tumor-specific labeling. These comparisons will show which injectable agent performs best under what circumstances, and whether completeness of fluorescence-guided resection is limited more by imperfect biochemical specificity of current contrast agents, or by inability to resolve and manually remove scattered or disseminated tumor cells. Photodynamic therapy (PDT) to kill off residual tumor cells in the surgical field before closure will also be tested. Completeness of initial tumor removal and any recurrence will be assessed postoperatively using the genetic reporters. Comparison with signals from injectable contrast agents and traditional survival measures should quantify how surgical outcomes depend on the thoroughness of tumor cell removal, how much improvement results from current injectable contrast agents vs. genetically perfectly labeling, whether PDT helps, how well can current injectable agents monitor recurrence, and what materials or procedures most need improvement.

项目总结