2011-01-012024-05-13https://scholars.lib.ntu.edu.tw/handle/123456789/648615摘要：神經母細胞瘤是源於脊索神經分枝的一種癌症。半數以上在腹部發現，偶而可在胸部、頸、骨盆或頭部發現。此種腫瘤為孩童第四種常見之腫瘤，全台灣每年佔兒童癌症的百分之6~8 的發病率，約有30 位新個案發生。通常是從腎上腺髓質或是由交感神經節以腹部腫瘤形式出現，但神經母細胞瘤生長快速並容易轉移。70%的病童，在症狀出現，被診斷前便已發生了轉移。治療方式多採合併療法，包括手術治療、放射線治療和化學藥物治療、自體骨髓移植治療，但仍然有七成的病童會在五年內陸續復發，五年存活率只有10-20%。而復發後的腫瘤多產生抗藥性，對化學治療反應不佳。I-/123,131 MIBG 能與腎上腺素受體結合，且具有高度特異性碘標記，在臨床上己被公認對於神經元源起之腫瘤，具十分有效之診斷定位功能，所以在神經母細胞瘤的診斷、轉移追蹤上已經是公認的標準檢查，而且顯影強度可做為腫瘤和骨髓內轉移治療效果評估。新的神經母細胞瘤治療方向就是，利用MIBG 對神經母細胞瘤的專一性，加上具有細胞毒性的放射性元素，把神經母細胞瘤細胞殺死，但對正常細胞影響較少，提高療效、降低副作用，其治療反應有4 成左右(10-80%)。主要的副作在於骨髓毒性，造成全乏血球症。另外氟18 左旋多巴（6-[18F]fluoro- levo-dopa，簡稱 18F-dopa）會由神經內分泌細胞所吸收和儲藏於細胞內，進而被aromatic acid decarboxylase （簡稱AADC）代謝成氟18 多巴胺（18F-dopamine）和其他神經傳導物質，因此理論上18F-dopa 可以用在神經母細胞瘤的特異性功能性造影，因此在18F-dopa 正子造影可以比一般正子造影更具專一性和診斷價值。本實驗計畫在2009 年8 月核研所進行I-/123 MIBG 之標幟研究與毒性試驗及品管分析方法建立成功，臺大醫院開始對新發病和現有病人進行I-123MIBG、F18DG、F18DOPA 造影，至2010 年1 月已進行17 例19 次I-123 MIBG、F18DG、F18DOPA 造影，並於發表論文於2010 年六月5-9 日美國鹽湖城舉行之北美第57 屆核子醫學年會，獲頒一般臨床專業組壁報論文之第一、二名。同年六月21-24 日在瑞典斯德哥爾摩舉行之神經母細胞瘤尖端研究會議上，獲頒臨床組最佳口頭論文獎。<br> Abstract: Neuroblastomas are the most common extracranial solid tumor of childhood, accountingfor 8% to 10% of all childhood cancers. Neuroblastomas are one of several tumors thatarise in neural crest cells, occurring in cells that give rise to the sympathetic nervoussystem. The tumor is highly variable in presentation and response. Approximately 50%of infants and 70% of patients over 1 year of age present with metastatic disease at thetime of initial diagnosis. Patients with low stage disease ( Evan’s stage I and II ) haveextremely favorable response rates to surgical resection alone ( survival > 90 % ). Onthe other hand, advanced stage neuroblastomas ( Evan’s stage III and stage IV ) havemuch poorer response and survival rates. The 5 year survival for children withmetastatic disease ( Evan’s stage IV ) is less than 25%, even when treated with intensivechemotherapy and autologous bone marrow transplantation . Patients who fail torespond to initial induction therapy, or patients who relapse, have less than 10% diseasefree survivals even with autologous bone marrow transplantation . Newer approachesfor treating such poor risk patients are needed. This protocol will examine the use of aradio-pharmaceutical agent, 131-I MIBG, that selectively concentrates withinneuroblastoma cells.Metaiodobenzylguanidine (MIBG) is an aralkylguanidine which is structurally similarto the neurotransmitter norepinephrine, and the ganglionic blocking agent guanethidine.Scintigraphic studies in the early 1980’s confirmed the effectiveness of MIBGlocalization of pheochromocytomas, neuroblastomas, and other neuroendocrine tumors.Approximately 90% of neuroblastomas will exhibit uptake of radiolabeled MIBG.Uptake is well-described in both primary tumors and metastatic sites.As early as the 1980’s MIBG scans began use for more than just tumor visualizationpurposes. By 1992 more than 300 patients had been treated at centers in Europe, theUniversity of Michigan, and University of California San Francisco with 131-I MIBGfor therapeutic purposes. Response rates have ranged from 10-50%, but the definition ofresponse has been highly subjective and variable, ranging from pain relief or decreasedcatecholamine secretion, to documented disappearance of lesions by imaging studies.Non-hematological toxicity, even at substantial MIBG doses, has usually been minimal.Nineteen patients with neuroblastoma were enrolled in this study.From 2009 August to 2010 January, 17 children with clinical diagnosis of neuroblastictumors were included and received 19 sets of scans. Their ages ranged from 0.5-12.8years old. All patients had F-18-DOPA PET scan. Three patients were primarydiagnosis/staging of disease and 16 cases were restaging of disease. Three primarydiagnosis patients showed positive uptake of F-18-DOPA in primary and metastasislesions. In restaging patients, five patients without uptake of F-18-DOPA showednegative standard imaging studies. Eleven patients with uptake of F-18-DOPA showedonly 6 positive I123-MIBG and 7 positive FDG PET/CT. In organ-region-specificanalysis, there were different uptake pattern in 3 imaging studies.神經母細胞瘤18F-dopa正子造影Neuroblastoma18F-FDOPApositron emission tomographysensitivity and specificity