Acquired Multi-Drug Resistance

获得性多重耐药性

• 批准号: 8555450
• 负责人: Janet F. Eary
• 金额: $ 11.83万
• 依托单位: UNIVERSITY OF WASHINGTON
• 依托单位国家: 美国
• 财政年份: 1998
• 资助国家: 美国
• 起止时间: 1998-05-12 至 2016-08-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/8555450
• 关键词: Acute Myelocytic Leukemia; Adjuvant Therapy; Adriamycin PFS; Affect; Aftercare; Anthracyclines; Area Under Curve; Biodistribution; Biological Assay; Blood; Blood flow; Brain; Cancer Biology; Cell physiology; Cells; Chemotherapy-Oncologic Procedure; Clinical Research; DNA Intercalation; Data; Development; Doxorubicin; Drug Delivery Systems; Drug Kinetics; Drug resistance; Early treatment; Effectiveness; Environment; Epirubicin; Equilibrium; Exposure to; Failure; Genomics; Histologic; Hypoxia; Idarubicin; Image; Injection of therapeutic agent; Kinetics; Label; Lead; Link; Malignant Neoplasms; Malignant neoplasm of pancreas; Measures; Mediating; Membrane; Methods; Modeling; Multi-Drug Resistance; Neoadjuvant Therapy; Neoplasm Metastasis; Noise; Nuclear; Observational Study; Outcome; Oxygen; P-Glycoprotein; Patients; Pharmaceutical Preparations; Physiological; Pilot Projects; Positron-Emission Tomography; Property; Protocols documentation; Pump; Radiopharmaceuticals; Recurrent disease; Regimen; Relative (related person); Reproducibility; Resistance; Solid Neoplasm; Specificity; Stomach Carcinoma; Survival Analysis; System; Taxane Compound; Testing; Therapeutic; Tissues; Treatment Effectiveness; Up-Regulation; Verapamil; Water; Xenobiotics; base; cancer type; chemotherapeutic agent; chemotherapy; dosimetry; gemcitabine; lipophilicity; molecular imaging; resistance factors; response; sarcoma; taxane; tumor; uptake

Anthracycline based therapy is a mainstay for many patients with solid tumor cancers. However, many of these tumors have variable levels of multiple drug resistance (MDR) transporters that reduce treatment effectiveness. The P-glycoprotein (Pgp) system specifically acts as a membrane pump to exclude anthracyclines and other common chemo therapeutics from intracellular accumulation. The activity of this transporter system can be up-regulated after exposure to anthracycline treatment and this is a suspected variable in treatment resistance and failure. In this project, we will quantify Pgp activity using a known transporter substrate, [[11]C]-verapamil, for tumor imaging. The uptake kinetics of this imaging agent can be used to quantify tissue Pgp activity when the tumor area under the curve from 0 to 20 min (AUC{0-20}) is normalized to the same AUC for blood. Imaging in sarcoma patients showed a range of [

基于蒽环类药物的治疗是许多实体瘤患者的主要治疗手段。然而，这些肿瘤中的许多具有不同水平的多药耐药(MDR)转运体，从而降低了治疗效果。P-糖蛋白(PGP)系统专门充当膜泵，将蒽环类药物和其他常见的化疗药物排除在细胞内积聚之外。这个转运蛋白系统的活性在接受了蒽环类药物治疗后可以被上调，这是治疗抵抗和失败的一个可疑变量。在这个项目中，我们将使用一种已知的转运蛋白底物[[11]C]-维拉帕米来量化PGP的活性，用于肿瘤成像。当肿瘤在0-20min曲线下的面积(AUC{0-20})归一化到相同的AUC时，这种显像剂的摄取动力学可以用来定量组织Pgp的活性。肉瘤患者的影像显示了一系列[