近年來相關缺氧細胞造影劑之研究，18F□Misonidazole(18F□MISO)一直佔有相當重要之地位。此藥物對缺氧細胞有特異性積聚；故為一甚佳之缺氧造影劑，同時為一輻射增敏劑，亦可作為癌症治療藥物。18F為正子放射性同位素，必須利用迴旋加速器設施生產。且須使用價格昂貴的PET造影設備，使得18FMISO無法廣泛應用於臨床上。
[99mTc(CO)3(H2O)3]+，為近年來新興之鎝99m標誌前趨物，其高標誌效率與高穩定性，及可與雙牙基、三牙基之配位子相結合之特性頗受核醫界重視。於本研究中，試圖合成Misonidazole（MISO）配位子與[99mTc(CO)3(H2O)3]+標誌前趨物，並嘗試將 [99mTc(CO)3(H2O)3]+與MISO結合。藉由高效能液相層析儀（HPLC）、薄層層析法（TLC）、電泳（Electrophoresis）等分析方法以了解放射化學特性，再以缺氧細胞吸收試驗評估未來此藥物應用於SPECT核醫缺氧造影藥物之可能。

結果顯示，[99mTc(CO)3(H2O)3]+ 在HPLC滯留時間( Retention time)為4 分鐘，薄層層析法（TLC，MeOH/HCl (95/5 v/v)）Rf值為0.35，電泳顯示為帶正電，在細胞缺氧實驗中，富氧吸收比例較高；[99mTc(CO)3(H2O)3]+與MISO結合所形成之錯合物在HPLC滯留時間為10分鐘，薄層層析法（TLC，MeOH/HCl (95/5 v/v)）Rf值為0.7，電泳為電中性，在細胞缺氧實驗中，缺氧吸收比例較高。由以上結果証實fac-99mTc(CO)3已成功地標誌上MISO，並在缺氧細胞中有特異性吸收，對未來應用於SPECT 缺氧造影藥物之潛力，值得更進一步探討。

18FMISO has played an important role as a hypoxic tracer, presenting with a high specific accumulation in hypoxic cells. 18F is a position emitting nuclide and generally produced from a cyclotron. 18F l led radiopharmaceuticals associated with expensive PET scan, would be restricted in clinical use for patients.
[99mTc(CO)3(H2O)3]+ was recently developed as an effective 99mTc labeling precursor, featured with high stability, highly labeling efficiency, and readily coordinating with bidentate or tridentate ligands with N, O and S donors. In this study, it has been attempted to label 99mTc in misonidazole (MISO), a hypoxic agent, using [99mTc(CO)3(H2O)3]+ as the precursor. Radiochemical characterization for the novel 99mTc labeled MISO complex was conducted via high performance liquid chromatography (HPLC)、 thin layer chromatography (TLC) ,and electrophoresis. Cell uptake test has been performed with tumor cells under aerobic and hypoxic conditions in order to assess the efficacy of 99mTcCO3 □ MISO as a hypoxic agent.

In HPLC , [99mTc(CO)3(H2O)3]+ is located at retention time = 4 min. In TLC, the 99mTc species is located at Rf = 0.3. In electrophoresis, it is prone to be positive. In cell uptake test, [99mTc(CO)3(H2O)3]+ presents higher uptake in tumor cells under aerobic condition than under hypoxic condition. For 99mTc(CO)3MISO species by labeling [99mTc(CO)3(H2O)3]+ in MISO, the results of radiochemical characterization are as follows. In HPLC, the 99mTc labeled MISO is located at retention time = 10 min. In TLC the 99mTc-complex species is located at Rf = 0.7. In electrophoresis, it presents to be neutral. In cell uptake test, 99mTc(CO)3MISO displays higher uptake under hypoxic condition than under aerobic condition.

In conclusion, this work has demonstrated the labeling of MISO with fac-99mTc(CO)3 for the first time. The novel 99mTc(CO)3MISO species exhibits the potential as a hypoxia tracer. It is worthy to evaluate furthermore the 99mTc labeled MISO complex as a hypoxia imaging agent for clinical use.

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