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標題: 正電胺基酸應用於111In-DOTATOC對腎臟吸收之探討
Discussion of Renal uptake of 111In-DOTATOC by Basic Amino Acid
作者: 陳俊雄
Chen, Chun-Hsiung
amino acid
出版社: 獸醫學系
摘要: 體抑素 ( somatostatin ) 受體已被發現存在於許多不同種類腫瘤,包括神經內分泌腫瘤,以及神經系統、乳房、肺部和淋巴組織腫瘤等,這個發現啟發了放射線標誌體抑素衍生物在這類腫瘤的診斷及治療上的運用。一種命名為DOTATOC的體抑素衍生物可以很容易且穩定的和放射線同位素111In標誌在一起;由於111In-DOTATOC具有腎毒性,本研究應用正電胺基酸來比較腎臟吸收之影響,以及評估111In-DOTATOC在生物體內的藥物動力學以及體內輻射劑量,以滿足衛生署之臨床試驗所須具備之臨床前動物試驗資料,期能早日應用於臨床,造福病患。材料與方法:本研究使用24隻大鼠,分成4組,分別於注射1 MBq 111In-DOTATOC後的0.5、4、24和48小時,利用γ閃爍造影捕捉影像並將其犧牲,取下體內不同部分組織秤重,並測定放射強度以計算組織放射濃度。在腎臟試驗使用16隻大鼠,配合111In-DOTATOC進行Lysine、Histidine以及Arginine腹腔注射,並以生理食鹽水做為對照使用,4小時後將其犧牲,測定組織放射濃度,比較腎臟吸收情形。結果:造影後發現,腫瘤組織具有高度輻射劑量,ROI 有不錯的表現,且經過48小時,腫瘤組織仍可清晰判讀。在輻射生物計數顯示,腫瘤團塊的藥物吸收濃度明顯高於肌肉組織,不會因時間的改變而明顯遞減。在腎臟部份顯示,給予Lysine對腎臟毒性侵襲性最少,具極佳腎臟保護性;而Histidine於數據中顯示保護結果優於Arginine僅次於Lysine;其中Arginine的效果保護最差。
Somatostatin receptors have been identified in different kinds of tumors such as neuroendocrine tumors and tumors of the central nervous system, breast, lung and lymphatic tissue. These observations have served as the biomolecular basis for the clinical use of radiolabelled somatostatin analogues for diagnostic and radionuclide therapy applications. DOTATOC, a somatostatin analogue, has been found to be easily and stably labelled with 111In for purposes. Because of 111In -DOTATOC has kidney toxicity, this research uses positive charge amino acid to compare the influence that the kidney absorb, and assess 111In-DOTATOC pharmacokinetic and biodistribution. Material and method: Twenty four rats will be divided into four groups. They will be slaughtered at 0.5, 4, 24 and 48 hrs after injection, samples of various organs will be counted to calculate the tissue concentration dose. Using 16 rats in the kidney test, cooperate with 111In-DOTATOC injects Lysine, Histidine and Arginine. Sacrifice it 4 hours later, determine the radiating. Result: by scintigraphy, it has high radiation dosage in tumor, and the ROI value is very high. Show in the kidney experiment, offer Lysine to the kidney toxicity attacking at least, have extremely good kidney protection properties; and Histidine shows in the data that the result of protecting is superior to Arginine and second only to Lysine; among them it is the worst that the result of Arginine is protected.
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