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研究生:陳昱睿
研究生(外文):Yu-Jui Chen
論文名稱:轉譯研究新典範:應用18F-FDG於自發癌症動物模型
論文名稱(外文):New Translational Research Paradigm: To Apply 18F-FDG for Canine Spontaneous Cancer Model
指導教授:吳東信
指導教授(外文):Tung-Hsin Wu
學位類別:碩士
校院名稱:國立陽明大學
系所名稱:生物醫學影像暨放射科學系
學門:醫藥衛生學門
學類:醫學技術及檢驗學類
論文種類:學術論文
論文出版年:2018
畢業學年度:107
語文別:中文
論文頁數:83
中文關鍵詞:癌症轉譯醫學自發性癌症動物模型18F-FDG PET/CT
外文關鍵詞:CancerTranslational medicineSpontaneous cancer model18F-FDG PET/CT
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研究背景:
寵物犬與人類有相似的癌症發展模式,可作為轉譯研究的自發性癌症動物模型。正子電腦斷層攝影(PET/CT)是連結寵物動物與人類癌症轉譯的關鍵性橋樑。本研究主要目的希望將人類醫學已發展成熟的PET/CT造影經驗,平行轉譯至臨床癌症的寵物犬作為動物模型,建立癌症疾病研究之分子轉譯影像平台。
材料與方法:
本研究利用超音波、X光及電腦斷層初診25例疑似自發性罹癌犬隻,再依病理切片區分為:非惡性腫瘤(n=3)、肉瘤(n=6)、癌(n=9)、黑色素瘤(n=3)及淋巴瘤(n=4)五個群組。經PET/CT取像後進行診斷及治療策略的再分析。並將正常器官及原發病灶對18F-FDG的攝取,做四種等級量化:無攝取、輕度攝取、中度攝取與高度攝取。同時評估SUVmax、SUVmean與TBR三種影像定量參數在惡性腫瘤鑑別的準確性。
結果:
非惡性腫瘤對於FDG僅具有輕微程度的攝取情形(SUVmean≦2.5);大部分惡性腫瘤(n=19)呈現中度以上之攝取程度(SUVmean≧2.5)。確診為惡性腫瘤案例中,高逹18例PET/CT發現疑有遠端轉移,使得獸醫師在診斷及治療策略上皆須作改變。正常器官量化結果,寵物犬在大腦與心肌的攝取相較於人類的生物分佈降低近30%,主因可能是犬隻施打麻醉造成葡萄糖代謝抑制。SUVmax、SUVmean與TBR的ROC曲線下面積(AUC)分別為:0.848、0.788與0.727。
討論與結論:
本研究成功使用18F-FDG PET/CT對寵物犬自發性癌症進行定性與定量之評估。透過PET/CT確實能對寵物犬之自發性癌症做出更精確的診斷,在遠端轉移及復發病灶上更具有良好的檢測能力。與人類近似的18F-FDG生物分佈,顯示寵物犬可作為自發性疾病動物模型的可行性。SUVmax有最高的AUC = 0.848、靈敏度= 81.8及特異性= 100,可作為鑑別惡性腫瘤的最佳參考指標。本研究應為全台灣首度使用大量自發性癌症寵物犬在PET/CT的轉譯研究,未來將持續進行,累積更多的案例與經驗,朝向轉譯醫學新典範邁進。
Background:
Pet dogs have a similar pattern of cancer development as human which can provide more appropriate spontaneous cancer model for translational studies. PET/CT (Positron Emission Tomography/Computed Tomography) is the critical bridge for linking animals to human in translational research. The aim of this pilot study is to transfer the mature PET/CT imaging experience in human medicine to pet dogs as a molecular imaging platform for cancer translational research.
Material and methods:
Twenty-five patients with suspected cancer diagnosed by ultrasound, X-ray and computerized tomography were divided into five groups according to pathological results, namely: non-malignant tumor (n=3), sarcoma (n=6), carcinoma (n=9), melanoma (n=3), and lymphoma (n=4). The diagnosis and treatment protocols were reevaluated after PET/CT imaging, and the uptake values of 18F-FDG in normal organs and primary lesions were quantified in four grades: None, Mild, Moderate, and Intense. The accuracy of three quantitative parameters of SUVmax, SUVmean and TBR to identify malignant tumors were also evaluated.
Result:
Non-malignant tumors had only mild FDG uptakes (SUVmean≦2.5) and most malignant tumors (n=19) had moderate to intense FDG uptakes (SUVmean≧2.5). In the cases of malignant tumor, eighteen of them were found having distant metastases in PET/CT images, which required changes in diagnosis and treatment strategies. The normal organ biodistribution results showed that the brain and myocardial uptake of pet dogs were reduced by nearly 30% compared with human. It might be that the dogs were given anesthesia resulted in inhibition of glucose metabolism. The area under the ROC curves (AUC) of SUVmax, SUVmean and TBR are: 0.848, 0.788 and 0.727, respectively.
Discussion and conclusion:
This study successfully used 18F-FDG PET/CT to evaluate the qualitative and quantitative diagnosis of canine spontaneous cancers. PET/CT can provide a more accurate diagnosis of spontaneous cancer in pet dogs, and also has good detection on distant metastasis and recurrent lesion. The 18F-FDG biodistribution similar to human also shows the feasibility of pet dog as a spontaneous cancer animal model. SUVmax has the highest AUC (=0.848), sensitivity (=81.8) and specificity (=100), which can be used as the best reference for identifying malignant tumors. To our best knowledge, this study should be the first translational study using PET/CT in a large number of spontaneous cancer pet dogs in Taiwan. It will continue to accumulate more cases and experiences in the future, and move towards a new paradigm of translational research.
誌謝 i
中文摘要 ii
英文摘要 iv
目錄 vi
圖目錄 viii
表目錄 x
第一章 緒論 1
1.1 轉譯醫學 1
1.2 轉譯科學家的新夥伴 2
1.3 高階醫療影像提供之轉譯平台 7
1.4 研究背景與目的 8
1.5 論文架構 8
第二章 市場分析與文獻回顧 9
2.1 伴侶動物高階醫療影像普查 9
2.2 克羅格原則 13
2.3 PET/CT的潛在價值 16
第三章 材料與方法 19
3.1 研究對像 19
3.2 收案流程 19
3.3 掃描參數 23
3.4 影像分析方式 24
3.4.1 感興趣區域(Region of Interest, ROI) 24
3.4.2 標準攝取值(Standard Uptake Value, SUV) 25
3.4.3 腫瘤背景比(Tumor-to-Background Ratio, TBR) 26
3.4.4 影像分級 26
3.5 統計分析 27
第四章 結果 28
4.1 非惡性腫瘤 28
4.2 肉瘤(Sarcoma) 31
4.2.1 原發腫瘤診斷與定量結果 31
4.2.2 血管肉瘤(Hemangiosarcoma) 35
4.3 癌(Carcinoma) 37
4.3.1 原發腫瘤診斷與定量結果 37
4.3.2 腺瘤(Adenocarcinoma) 41
4.3.3 肝細胞癌(Hepatocellular carcinoma) 45
4.3.4 甲狀腺髓質瘤(Medullary thyroid carcinoma) 47
4.4 黑色素瘤(Melanoma) 50
4.5 治療策略之改善 55
4.6 淋巴瘤(Lymphoma) 56
第五章 討論 63
5-1 18F-FDG PET/CT於犬自發性癌症之診斷 63
5.1.1 原發腫瘤之定量與分級 63
5.1.2 遠端轉移之偵測 65
5-2 自發癌症動物模型之可適性驗證 67
5-3 ROC曲線分析 72
5-4 不同定量參數之差異 75
第六章 結論 77
第七章 參考文獻 78
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