中文摘要

　　冷凍治療是一種最小侵入的治療手段，治療後會有一物理變化之冰球介面，可用作為治療的指標。冰凍固化後可以阻斷化學物質流動，很有潛力可以用於滯留藥物。但是它的缺點是，癌細胞在冰凍邊界的致死情況不容易控制。硼中子捕獲療法的優點是輻射射程短，大約只有一個細胞的大小；瓶頸是其藥物須選擇性聚集在腫瘤細胞內，且相鄰的正常組織藥物濃度不能太高。冷凍治療合併硼中子捕獲療法的二元療法 (binary therapy)，是一種使用兩種以上無毒的物質導入細胞造成組織壞死的一種療法。我們認為冷凍手術治療可以滯留藥物，而且這個藥物的濃度可以利用臨床上常用的電腦斷層影像來顯示。
　　因為一般二元療法之藥物不易在影像上觀測，因此利用電腦斷層影像可見之含碘造影劑伴隨一定比例之硼酸，用以研究冷凍手術進行中之冰球變化及評估藥物滯留行為。實驗分做四部份，首先是將造影劑稀釋成不同濃度，予已知濃度下之造影劑進行電腦斷層掃描看是否符合稀釋原則；其次，利用已摘除之新鮮豬腎經由腎動脈注射合併硼酸之造影劑及生理食鹽水，並同時進行冷凍手術模擬過程及電腦斷層影像監控。活體動物實驗利用26-31公斤之健康活豬，於手術房中進行動脈給藥及冷凍手術模擬，並於實驗後立即摘除腎臟進行電腦斷層影像觀察藥物分佈。最後取出體外豬腎模型及活體動物模型實驗後之樣本，分別對冰凍區及非冰凍區組織採樣以進行感應偶合電漿質譜儀之藥物濃度分析。
　　本研究證明冷凍手術有高濃度之藥物滯留效果，可以提高腫瘤區之藥物濃度，以改善硼中子捕獲療法藥物選擇性不佳之困擾。利用含碘造影劑當作示蹤劑於電腦斷層影像下，可以方便的監控及預估藥物濃度以避免治療過當或治療不足。雖然本初期研究尚無法證明冷凍手術合併硼中子捕獲療法之互補效果；冷凍手術可以滯留藥物的事實顯示，此二元療法非常有潛力於硼中子捕獲療法之應用。另外，未來若改變其他治療藥物，或是配合冷凍手術之冰球操控及多探頭技術，更可以設計出臨床需要之藥物滯留體積及形狀。

Abstract
　Cryosurgery aims to be a minimal invasive procedure .The changeable physical interface can be monitoring by the imaging modality during the frozen process which was the advantage of the cryosurgery. However, difficulty in controlling extent of killing in cryosurgery is the major problem. The radiation of boron neutron capture therapy (BNCT) has powerful cell toxicity and short range which equal to 10 m ( only one cell diameter). But highly selective distribution is not easy to achieve. We consider cryosurgery and binary therapy could be complementary to each other. And investigate the theoretical advantages in an ex vivo and in vivo porcine renal models with the computed tomography as the following.
　Because the drugs of the BNCT were not seen in the CT scan , So that we combined iodinated contrast media and boric acid to simulated the drugs retention in the cryosurgery. (1) A serial dilution of contrast medium were examination by the computed tomography, The CT number was retrieved after the computed tomography was done in estimation concentration of contrast medium. (2) Porcine kidneys were harvested freshly and a catheter was inserted into the cut end of the arteries for injections of the contrast medium ( contain boric acid) and methylene blue saline . Two other catheters were inserted in the renal vein and the ureter to drain out the fluid. Contrast medium and normal saline irrigation was done while doing cryosurgery at the same time. The distribution of the contrast medium was observed by computed tomography examination.(3) In vivo animal model , 26- to 31-kg pigs were submitted to the study of cryosurgery in retaining the contrast medium. After euthanized, the kidneys were kept frozen at -70℃, before computed tomography examination. (4) ICPMS analyzed the renal parenchyma tissue (frozen and non-frozen area) to estimated the concentrations of the boron and iodine. The correlation of the concentration of boron with CT number were studied.
　This experiment shows that cryosurgery could be used to retain iodine in the frozen area for a binary therapy in CT scan, which we believe it’s could be applied to other kind of drugs that we intended to use. The iodine could also be used as an indicator to estimate the extent of high concentrated in the frozen area. We can monitoring the drugs retention in the cryosurgical process and predict the concentration of the iodine (and non-iodine). The Future, we can control the cryosurgical procedural to make different retention volume and shape to suited the clinical application .

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