背景:腫瘤內部的缺氧細胞對於游離輻射之耐受性約為正常細胞的3倍，對於腫瘤之放射治療影響很大。鎝-99m-HL91為新研發非nitroimidazo1e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製劑在接腫sarcoma腫瘤小鼠之體內分佈。
方法:鎝-99m-HL91由自製配方凍晶小瓶力。入鎝-99m過鎝酸鈉標幟而成，放射化學純度大於98%0 C3H小鼠接 種肉瘤(KHTsarcoma) ，且腫瘤已成長達直徑約1公分者，經尾部靜脈注射鎝-99m-HL91後進行生物體分佈試驗法，計算各器官之%LD/g。給藥4小時後再進行全身加馬閃爍造影及自動放射顯影。
結果:體內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確實可以進入腫瘤內部。肝臟、腎臟與膀胱聚 集了大量的放射活性，顯示鎝-99m-HL91或其代謝物經由這些器官代謝、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。

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， 99mTc-2，2 '(1，4-diaminobutane) bis (2- methyl- 3-butanone) dioxime (HL91)， has recently been developed for imaging hypoxia. Its applications in oncology and myocardial ischemia are still under investigation. In this study we evaluated the in-vivo distribution of a 99mTc_ HL91 formulation on sarcoma-bearing mice.
Methods: 99mTc-HL91was prepared by reconstituting a lyophilized pre-formulated kit with 99mTc-pertechnetate. The radiochemical purity of 99mTc-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 1 cm in diameter. The biodistribution data of 99mTc-HL91， given by tail-vein injection， in m刮or organs of animal model were calculated in percent injected dose per gram organ (%I.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 and 30.4， respectively) at 2 h post-injection. Whole-body gamma image demonstrated plateau tumor-to-muscle ratio of 7.58 at 4 h after injection. Autoradiograms depicted significant uptake of 99mTc-HL91 in tumor mass. The accumulation of relatively large amount of radioactivity in the liver， the kidneys and the bladder revealed that 99mTc-HL91 might be metabolized or excreted through these organs. Since low uptake in the brain was observed， 99mTc-HL91 may not cross the blood brain barrier freely.
Conclusion: 99mTc-HL91 preparation with high radiochemical purity and good stability can be achieved from a preformulated lyophilized kit with high labeling efficiency. The preliminary biodistribution data support further studies on imaging tumor hypoxia.