Diagnosis and Management of Endocrine Neoplasia

内分泌肿瘤的诊断和治疗

• 批准号: 7591653
• 负责人: CHERYL A PICKETT
• 金额: $ 8.68万
• 依托单位: UNIVERSITY OF WASHINGTON
• 依托单位国家: 美国
• 资助国家: 美国
• 起止时间: 至 2011-08-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/7591653
• 关键词: Adrenal Glands; Avidity; Behavior; Bilateral; Biochemical; Biological Assay; Blood flow; Cessation of life; Clinical; Clinical Research; Defect; Diagnosis; Disease; Disease Progression; Effectiveness; Endocrine; Endocrine Gland Neoplasms; Endocrine Glands; Excision; Expression Feature; Functional Imaging; Goals; I131 isotope; Image; Imaging Techniques; In Vitro; Individual; Indolent; Intervention; Investigation; Iodides; Iodine; Kinetics; Knowledge; Lead; Lithium; Localized; Magnetic Resonance Imaging; Malignant - descriptor; Malignant Neoplasms; Malignant neoplasm of thyroid; Measurement; Measures; Metabolic; Metabolism; Methods; Molecular; Monitor; Neoplasm Metastasis; Neoplasms; Norepinephrine; Operative Surgical Procedures; Outcome; Parents; Pathological Staging; Patient Selection; Patients; Pheochromocytoma; Positron-Emission Tomography; Procedures; Radionuclide Imaging; Range; Recording of previous events; Refractory; Research Project Grants; Selection for Treatments; Sensitivity and Specificity; Site; Staging; Surgeon; Techniques; Testing; Therapeutic Agents; Thyroid carcinoma; Tissues; Tretinoin; Validation; Water; Work; analog; base; cancer therapy; clinical Diagnosis; clinical application; design; fluorodeoxyglucose positron emission tomography; improved; in vitro Assay; in vivo; intravenous injection; malignant endocrine gland neoplasm; metaiodobenzylguanidine; outcome forecast; radiotracer; response; size; tool; tumor; uptake

Radiotracer imaging and therapy has been a key tool for the management of many endocrine tumors, including thyroid cancer and pheochromocytoma. However, for both thyroid cancer and pheochromocytoma, more specific biochemical imaging approaches are needed to better localize these tumors and to direct treatment. We will investigate new PET based imaging techniques for these two tumor types. Radioiodine (131 I-iodide) is the mainstay of thyroid cancer therapy. However, up to 20% of patients have thyroid cancers that become refractory to 131 I, and these patients succumb to their disease. The ultimate goal is to cure thyroid cancer in these patients. We will develop approaches to characterize iodine kinetics in the tumors of individual patients using a combination of in vivo functional imaging and in vitro analysis of regulators of iodine transport, organification and effiux. This approach will be used to determine the defects in individuals with iodine-refractory thyroid cancer and to select approaches for improving the response to radioiodine. Dynamic 124 I-iodide PET after intravenous injection will be used to measure the kinetics of iodine delivery and retention by tumors, while simultaneous [15 O]-water imaging will be performed to evaluate tumor blood flow. FDG-PET imaging will be used to localize tumors and to provide information regarding metabolic activity and tumor behavior. Imaging parameters will be compared to in vitro analysis of tumor expression of features important in iodine uptake and retention. After validation, the method will be used to test whether specific therapeutic agents correct defects in iodine retention and improve 131 I therapy. In the case of pheochromocytomas, better localization and staging techniques are needed for planning surgical approach and post-surgical monitoring. 11 C-Metahydroxyephedrine (mHED), a norepinephrine analog, will be investigated as a radiotracer to provide superior image sensitivity and specificity over current approaches, including CT, MRI, and MIBG scintigraphy. The combination of mHED and FDG PET will be tested as an approach to detect pheochromocytoma with a broad range of biologic behavior. The sensitivity and specificity of mHED/FDG PET for localizing and staging pheochromocytoma will be tested, and imaging results will be correlated with biochemical analysis, surgical staging, pathological diagnosis and clinical outcome. These studies are anticipated to improve diagnosis, staging, and treatment selection for patients with thyroid cancer and pheochromocytoma and lead to new clinical applications of PET to endocrine neoplasia.

放射性成像和治疗一直是管理许多内分泌肿瘤（包括甲状腺癌和嗜铬细胞瘤）的关键工具。但是，对于甲状腺癌和 需要采用嗜铬细胞瘤，更具体的生化成像方法，以更好地定位这些肿瘤并指导治疗。我们将研究这两种肿瘤类型的新的基于PET的成像技术。放射性碘（131 I-碘化物）是甲状腺癌疗法的主要阶段。但是，多达20％的患者患有甲状腺癌，使131 I难治性，这些患者屈服于他们的疾病。最终目标是治愈这些患者的甲状腺癌。我们将使用体内功能成像和碘转运，有机化和EFFIUX的调节剂的体外分析的组合，开发出在个体患者肿瘤中表征碘动力学的方法。这种方法将用于确定缺陷 在患有碘 - 难治性甲状腺癌的个体中，并选择改善对放射碘反应的方法。静脉注射后的动态124 I-碘PET将用于测量碘递送和肿瘤保留的动力学，同时[15 O] - 水成像以评估肿瘤血流。 FDG-PET成像将用于定位肿瘤，并提供有关代谢活性和肿瘤行为的信息。成像参数将与对碘摄取和保留率重要的特征肿瘤表达的体外分析进行比较。验证后，该方法将用于测试特定的治疗剂在碘保留率中是否正确缺陷并改善131 I治疗。在嗜铬细胞瘤的情况下，需要更好的定位和分期技术来计划手术方法和手术后监测。 11 c-甲基羟基麻黄碱（MHED），一种去甲肾上腺素类似物，将作为放射性肾上腺素进行研究，以比当前方法（包括CT，MRI和MIBG Scintigraphy）具有出色的图像敏感性和特异性。 MHED的组合 FDG PET将作为一种检测具有广泛生物学行为的嗜铬细胞瘤的方法进行测试。将测试MHED/FDG PET对定位和分期嗜铬细胞瘤的敏感性和特异性，并将成像结果与生化分析，外科手术分期，病理诊断和临床结果相关。预计这些研究将改善甲状腺癌和嗜铬细胞瘤患者的诊断，分期和治疗选择，并导致PET在内分泌肿瘤中的新临床应用。