CLINICAL PET AND LABORATORY STUDIES OF ADRENERGIC TUMORS

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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.