鎝-99m-HL91于肉瘤小鼠之生物體分布研究

Biodistribution Sstudy of 99m Tc-HL91 in Sarcoma-Bearing Mice

夏建忠(Chien-Chung Hsia) ； 王信二(Hsin-Ell Wang) ； 魏孝萍(Shiaw-Pyng Wey) ； 劉仁賢(Ren-Shyan Liu) ； 沈立漢(Lie-Hang Shen)

《核子醫學雜誌》 16卷3期 (2003/09) Pp. 131-136

https://doi.org/10.6332/ANMS.1603.004

摘要

背景：腫瘤内部的缺氧細胞對於游離輻射之耐受性約爲正常細胞的3倍，射於腫瘤之放射治療影響很大。鎝-99m-HL91爲新研發非nitroimidazole類缺氧組織造影藥物，其在腫瘤及心肌缺氧的應用研究仍在進行。本研究評估自製鎝-99m-HL91製劑在接種sarcoma腫瘤小鼠之體内分佈。方法：鎝-99m-HL91由自製配方凍晶小瓶加入鎝-99m過鎝酸鈉標幟而成，放射化學純度大於98％。C3H小鼠接種肉瘤(KHTsarcoma)，且腫瘤已成長遠直徑約1公分者，經尾部静脈注射鎝-99m-HL91後進行生物體分佈試驗法，計算各器官之%ID./g。给藥4小時後再進行全身加馬閃爍造影及自動放射顯影。結果：體内分佈結果顯示腫瘤對血液及腫瘤對肌肉的放射活度比在注射鎝-99m-HL91後2小時分別達到最高值11.7及30.4。全身加馬造影結果顯示腫瘤對肌肉比在注射後4小時可高達最高值7.58。自體放射顯影結果證實鎝-99m-HL91確實可以進入腫瘤内部。肝臟、腎臟與膀胱聚集了大量的放射活性，顯示鎝-99m-HL91或其代谢物經由這些器官代谢、排泄。腦部的放射活性分佈極低，顯示鎝-99m-HL91可能無法通過正常之血腦障壁(bloodbrain barrier)。結論：自製鎝-99m-HL91具高標幟效率、高放射化學純度及安定性，初步試驗顯示可用於腫瘤缺氧組織造影的後續研究。

關鍵字

鎝-99m-HL91 ； 缺氧 ； 種瘤 ； 生物體分布

並列摘要

Backgrounds: The tolerance against radiation therapy of the hypoxic cells located inside tumor tissue has been estimated three folds than that of cells in normal oxygen level. This is the reason why hypoxia significantly disturbs the radiation therapy for tumors. A non-nitroimidazole-based radiotracer,(superscript 99m)Tc-2,2'(1,4-diaminobutane)bis(2-methyl-3-butanone)dioxime(HL91),has recently been developed for imaging hypoxia. Its applications in on cology and myocardial ischemia are still under investigation. In this study we evaluated the in-vivo distribution of a (superscript 99m)Tc-HL91 formulation on sarcoma-bearing mice. Methods:(superscript 99m)Tc-HL91 was prepared by reconstituting a lyophilized pre-formulated kit with (superscript 99m)Tc-pertechnetate. The radiochemical purity of (superscript 99m)Tc-HL91 was generally over 98% as determined by radio-thin layer chromatography(TLC).KHT sarcoma cells were transplanted into C3H mice. The study was conducted on the animals when the tumor grew up to 1cm in diameter. The biodistribution data of (superscript 99m)Tc-HL91,given by tail-vein injection, in major organs of animal model were calculated in percent injected dose per gram organ(%1.D/g).Whole-body scintigraphic imaging and subsequent autoradiography were performed at 4 h after radiotracer administration Results: The distribution data showed both tumor-to-blood and tumor-to-muscle ratios reached maximum(11.7 and30.4,respectively)at 2 h post-injection. Whole-body gamma image demonstrated plateau tumor-to-musde ratio of7.58 at 4 h after injection. Auto radiograms depicted significant uptake of (superscript 99m)Tc-HL91 in tumor mass. The accumulation of relatively large amount of radioactivity in the liver,the kidneys and the bladder revealed that (superscript 99m)Tc-HL91 might be metabolized or excreted through these organs. Since low uptake in the brain was observed,(superscript 99m)Tc-HL91 may not cross the blood brain barrier freely. Conclusion:(superscript 99m)Tc-HL91 preparation with high radiochemical purity and good stability can be achieved from a pre-formulated lyophilized kit with high labeling efficiency. The preliminary biodistribution data support further studies on imaging tumor hypoxia.

並列關鍵字

99m Tc-HL91 ； hypoxia ； tumor ； biodistribution