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CLINICAL PET AND LABORATORY STUDIES OF ADRENERGIC TUMORS

肾上腺素能肿瘤的临床 PET 和实验室研究

基本信息

批准号：
6497335
负责人：
BARRY L SHULKIN
金额：
$ 29.85万
依托单位：
UNIVERSITY OF MICHIGAN AT ANN ARBOR
依托单位国家：
美国
项目类别：
财政年份：
1991
资助国家：
美国
起止时间：
1991-04-01 至 2004-08-31
项目状态：
已结题

项目摘要

DESCRIPTION (From the Applicant's Abstract): Neuroblastomas and pheochromocytomas are tumors derived from tissues of the sympathetic nervous system. Neuroblastomas are common and highly lethal malignancies of children. Pheochromocytomas are an uncommon but curable source of hypertension and its associated morbidity, direct results from the excessive production of catecholamines. These tumors concentrate catecholamines and catecholamine analogs, and thus can be assessed scintigraphically utilizing specifically designed radiotracers. Epinephrine is a naturally occurring catecholamine product of the adrenal medulla and of some pheochromocytomas. When epinephrine is labeled with carbon-11, its distribution in vivo can be mapped noninvasivel in a variety of physiologic and pathophysiologic conditions using positron emission tomography (PET). The aim of this proposal is to evaluate the biodistribution of C-11epinephrine in patients with the neuroendocrine tumors neuroblastoma and pheochromocytoma, and to characterize the uptake and retention within tumors themselves. The applicants expect to show, by virtue o the superior image resolution of PET technology and the information provided b the distribution of C-11 epinephrine, an advance in ability to characterize these tumors. Utilizin C-11- epinephrine as a tracer of catecholamine uptake and storage, the applicants will examine the degree of tumor uptake by neuroblastomas as an indicator of histopathology, of prognosis and of N-myc and Bcl-2 proto-oncogen expression, in an effort to better characterize these lesions noninvasively. This information is anticipated to be useful in selection of therapeutic regimens appropriate for the expected degree of chemotherapy resistance. In patients with neuroblastoma undergoing radiation or chemotherapy, it is anticipated that serial studies will show that changes in tumor uptake of C-11 epinephrine reflect the tissue response to treatment and serve as an early indicator of therapeutic efficacy or failure. Such knowledge obtained early during the course of therapy would allow for prompt changes from ultimately unsuccessful therapeutic regimens to more promising combinations, or continuation of regimens with evidence of early success. In neuroblastoma cell lines, we will explore the mechanism of uptake and storage of epinephrine, and compare the retention and already characterized genetic alterations for additional index of prognosis. The applicants expect to show that the retentio of C-11 epinephrine within pheochromacytoma reflects catecholamine storage capacity, and thus could identify those tumors with greatest tendency for bloo pressure lability and dangerous catecholamine surges. If such information abou neuroblastomas and pheochromocytomas can be made available noninvasively by PE scanning with C-11 epinephrine, the understanding of the pathophysiologic process and the management of patients with these neuroendocrine tumors could be substantially improved.

描述（来自申请人的摘要）：神经母细胞瘤和神经母细胞瘤嗜铬细胞瘤是源自交感神经组织的肿瘤系统神经母细胞瘤是一种常见的高致死性恶性肿瘤，孩子嗜铬细胞瘤是一种罕见的，但可治愈的来源，高血压及其相关的发病率，直接结果从过度生产儿茶酚胺。这些肿瘤浓缩了儿茶酚胺，儿茶酚胺类似物，因此可以利用免疫组织化学方法进行评估。专门设计的放射性示踪剂肾上腺素是一种天然存在的肾上腺髓质和某些嗜铬细胞瘤的儿茶酚胺产物。当肾上腺素用碳-11标记时，其在体内的分布可以被测量。在各种生理和病理生理学中映射非侵入性使用正电子发射断层扫描（PET）的条件。的目的建议评价C-11肾上腺素在患者体内的生物分布神经内分泌肿瘤神经母细胞瘤和嗜铬细胞瘤，表征肿瘤自身内的摄取和保留。的申请人期望凭借PET的上级图像分辨率技术和信息提供的B的分布 C-11肾上腺素，表征这些肿瘤的能力的进步。利用C-11-肾上腺素作为儿茶酚胺摄取和储存的示踪剂，申请人将检查成神经细胞瘤的肿瘤摄取程度，组织病理学、预后以及N-myc和Bcl-2的指标原癌基因表达，以更好地描述这些病变非侵入性地。这些信息预计将有助于选择适合预期化疗程度的治疗方案阻力在接受放射治疗的神经母细胞瘤患者中，化疗，预计系列研究将显示，肿瘤对C-11肾上腺素的摄取反映了组织对治疗的反应并作为治疗功效或失败的早期指标。等在治疗过程中早期获得的知识将允许及时从最终不成功的治疗方案到更有希望的治疗方案联合用药，或继续使用早期成功证据的方案。在神经母细胞瘤细胞系中，我们将探索摄取和肾上腺素的储存，并比较保留和已经表征遗传改变作为额外的预后指标。申请人期望表明嗜铬细胞瘤内C-11肾上腺素的保留反映了儿茶酚胺的储存能力，因此可以识别那些具有最大的血液压力不稳定性和危险性倾向的肿瘤儿茶酚胺激增如果这些关于神经母细胞瘤的信息，嗜铬细胞瘤可以通过PE扫描进行非侵入性检查， C-11肾上腺素，病理生理过程的理解，这些神经内分泌肿瘤患者的管理可能是大大改善。