CLINICAL PET AND LABORATORY STUDIES OF ADRENERGIC TUMORS

描述(摘自申请者摘要)：神经母细胞瘤和 嗜铬细胞瘤是起源于交感神经组织的肿瘤。 系统。神经母细胞瘤是一种常见且致命性极高的恶性肿瘤。 孩子们。嗜铬细胞瘤是一种不常见但可治愈的来源 高血压及其相关发病率，由过度的直接结果 儿茶酚胺的生产。这些肿瘤浓缩儿茶酚胺和 儿茶酚胺类似物，因此可以用闪烁技术进行评估 专门设计的放射性示踪剂。肾上腺素是一种自然产生的 肾上腺髓质和一些嗜铬细胞瘤的儿茶酚胺产物。 当肾上腺素被碳-11标记时，它在体内的分布可以是 在多种生理学和病理生理学中的无创性定位 条件下使用正电子发射断层扫描(PET)。这样做的目的是 建议评估C-11肾上腺素在患者体内的生物分布 神经内分泌瘤、神经母细胞瘤和嗜铬细胞瘤，并 描述肿瘤本身内的摄取和滞留。这个 申请者希望凭借PET卓越的图像分辨率来展示 技术和信息由分布在 C-11肾上腺素，这是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 申请者将检查神经母细胞瘤摄取肿瘤的程度如下 组织病理学、预后及N-myc和Bcl2指标的研究 原癌基因表达，以更好地描述这些病变 非侵入性的。这一信息预计将在选择 与预期化疗程度相适应的治疗方案 抵抗。神经母细胞瘤患者接受放射治疗或 化疗，预计系列研究将显示这种变化 肿瘤摄取C-11肾上腺素反映组织对治疗的反应 并可作为治疗效果或失败的早期指标。是这样的 在治疗过程中及早获得的知识将使 从最终失败的治疗方案到更有希望的变化 有早期成功证据的联合用药或继续用药。 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，并比较其滞留和已表征 基因改变可作为预后的附加指标。申请者 预计将显示嗜铬细胞瘤内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 最易发生血液压力不稳定和危险的肿瘤 儿茶酚胺激增。如果这些关于神经母细胞瘤和 嗜铬细胞瘤可以无创地通过PE扫描获得 C-11肾上腺素，对病理生理过程的理解和 这些神经内分泌肿瘤患者的治疗可能是 有很大的改善。

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.