Ho-166-Acetylacetonate-Lipiodol核醫藥物研制及其做爲肝癌體內輻射治療之細胞實驗評估

Preparation and in Vitro Evaluation using Holmium-166-acetylacetonate-lipiodol as a Potential Agent for the Internal Radiation Therapy of Hepatocellular Carcinoma

周鳳英(F. I. Chou) ； 戚謹文(C. W. Chi) ； 衛元耀(Y. Y. Wei) ； 蔣淑娟(S. C. Chiang) ； 謝明學(M. S. Shieh) ； 雷永耀(W. Y. Lui)

《放射治療與腫瘤學》 4卷3期 (1997/09) Pp. 185-193

https://doi.org/10.6316/TRO/199704(3)185

摘要

目的：本研究之目的是以中子活化之Ho-166 研製肝癌治療核醫藥劑，測試藥物之穩定性及對肝癌細胞之作用。
材料與方法：將研製之Ho-165-acetylacetonate (Ho-165-AcAc)藥物於清華大學水池式反應器進行中子照射，使HO-165轉換成釋放高能β輻射之Ho-156核種，以多頻道能譜分析儀分析藥物核種強度及純度。所得之Ho-166-AcAc 以碘化罌粟油攜帶之，並於血清中測試其穩定性，以培養之人類肝癌細胞(HepG2 cells)探討藥物對肝癌細胞之作用。
結果：Ho-165-AcAc置於反應器之垂直照射管中照射10小時，所生成之Ho-165-AcAc放射比活性可達16-18 mCl/50 mg，經120小時血清中中試結果顯示Ho-166-AcAc-lipiodol中約有98％的Ho-166保存在其油相之中。HepG2、細胞在Ho-165-AcAc-lipiodol處理24小時後，顯微鏡下可見有大量Ho-165-AcAc-liplodol脂球積聚其中，此時細胞內的Ho-165-AcAc量為1.3µg/10^6 cells。由施藥時Ho-166-AcAc-lipiodol之放射比活性可以估算得細胞中Ho-166-AcAc-lipiodol之放射活性。
結論：Ho-166-acetylacetonate-lipiodol攜帶高能β輻射釋出核種，於血清之穩定性高，細胞實驗結果顯示，Ho-165AcAclipiodol可為肝癌細胞所大量攝入，此體外研究提供未來體內實驗之基本資料，此Ho-166AcAc-lipiodol藥物應可提供肝癌一新的體內輻射治療機會。

關鍵字

Ho-166-AcAc-lipiodol ； 肝癌細胞 ； 核醫藥劑

並列摘要

Objective: The objective of this research was to synthesize and prepare radiopharmaceuticals containing neutron-activated Ho 166. The in vitro stability of Ho-166-radiopharmaceuticals was tested, and the interaction of the radiopharmaceuticals with hepatoma cells was investigated.
Materials and Methods: In order to generate Ho 166, the non-radioactive Ho-165-acetylacetonate (Ho-165-AcAc) was prepared and irradiated in the Tsing Hua Open-Pool Reactor. Multiple channel analyzer was used for analysis of the radioactivity and the purity of the Ho-166-AcAc. Lipiodol was used as a carrier of Ho-166-AcAc. The stability of Ho-166-AcAc-lipiodol in serum was tested. The interaction of Ho-l65-AcAc lipiodol with human hepatoma cells (HepG2 cells) was investigated.
Result: In this study, the prepared Ho-l65-AcAc samples were irradiated in the nuclear reactor for up to 10 hr and yielded 16-l8mCi/SOmg of specific activity. In addition, in vitro analysis of the stability of Ho-166-AcAc-lipiodol in plasma revealed a 98% retention of Ho-166 in the Ho-l66-AcAc-lipiodol after 120 hr. In vitro treatment of HepG2 cells for 24 hr with Ho-165-AcAc-lipiodol resulted in a retention of 1.3µg of Ho-165-AcAc in 106 cells. Thus, from the specific activity of Ho-166-AcAc-lipiodol the potential radioactivity of Ho-166 in HepG2 cells can be evaluated.
Conclusion: Ho I 66-AcAc-lipiodol contained sufficient high energy J3 emitter and has a high stability in serum. in vitro cell culture analysis showed that large amount of I-lo-165-AcAc-lipiodol can be uptake by hepatoma cells. Results of this in vitro study provided important basic information for future development and in vitro tests. The Ho-I 66-AcAc-lipiodol has potential for future hepatoma therapy.

並列關鍵字

Ho-166-AcAc-lipiodol ； Hepatoma cells ； Radiopharmaceuticals