目的：以甲殼素型熱敏感式水凝膠合併放射性鍊－188錫膠體及化療藥物Doxorubicin (Dox)，發展新型局部放射化學治療藥物。材料與方法：以甲殼素(C)及甘油磷酸鹽(GP)製備熱敏感性水凝膠系統(C/GP system)用來合併錸－188錫膠體及Dox。利用氣化亞錫及新鮮流洗之過錸酸鹽(Na^188 ReO4)於100℃反應2小時製備錸－188錫膠體。於體外釋放研究中，透過控制組與C/GP/Dox之體外釋放實驗去評估C/GP水凝膠維持Dox藥物釋放之能力。C/GP/鍊－188錫膠體及C/GP/過錸酸鹽（控制組）二組藥物透過在大白鼠後肢上直接肌肉注射(0.6 mCi/0.3 ml)，並於注射後0、3、24及48小時利用加馬攝影儀進行造影。結果：呈流動液態之甲殼素型熱敏感性水凝膠可在室溫下製備完成。當受熱達37℃時，水凝膠可於5分鐘內轉相成穩定之凝膠態。甲殼素型水凝膠有維持及延長化療藥物釋放之能力（長達36小時）。鍊－188賜膠體藥物於100℃反應2小時後，標幟效率可達93.9±0.6%，平均粒徑爲12.1±1.2 μm，粒徑小於1 μm爲7.2±1.5%。錸－188錫膠體以3,000 rpm 離心10分鐘純化後，其放射化學純度大於98%。閃爍造影結果顯示C/GP/鍊－188錫膠體於注射後48小時，藥物依然可維持於局部位處而無明顯擴散。結論：本研究已建立甲殼素型熱敏感性水凝膠及錸－188錫膠體藥物之製備技術暨藥物系統組合之體外藥物釋放之動力學研究。將進一步評估以錸－188熱凝膠放射藥物進行體內治療之可行性。

Objective: To establish a novel and effective treatment mode of regional radiochemotherapy by using chitosanbased thermosensitive hydrogel system loaded with 188Re-tin colloid and Doxorubicin drug (Dox). Methods: Chitosan (C) and β-glycerophosphate (β-GP) were used to establish a thermosensitive hydrogel (C/GP) system for controlled local delivery of 188Re-tin colloid and Dox. 188Re-tin colloid were prepared in a vial, consisted of SnCI2•2H2O and freshly eluted perrhenate, for 2 h at 100℃. In vitro release study of Dox from hydrogel system was performed at 37℃ with pH 7.4 PBS medium. Kinetic distribution of 188Re-tin colloid in rats after intramusclular injection was followed by planar scintigraphy at 0, 3, 24 and 48 h after injection. Results: The C/GP hydrogel system prepared in our Lab. was able to undergo rapid sol-gel transition within 5 mm. after it was brought in the environment of 37℃. The in vitro release study of C/GP/Dox showed that the CIGP hydrogel significantly sustained the release of Dox anticancer drugs up to 36 h. The labeling efficiency of 188Re-tin colloid was 93.9±0.6%, and could be increased more than 98% following centrifugation with 3,000 rpm for 10 mm. The average particle size of 188 Re-tin colloid was 12.1±1.2 pm, with only 7.2±1.5% less than 1 μm. Scintigraphic study indicated that 188Re-tin colloids contained in C/GP system was able to be localized around the injection site for up to 48 h post injection. Conclusion: The preparation and characterization methods of a chitosan-based hydrogel system containing Doxorubicin and 188Re-tin colloids were well established. Our study demonstrated that the system could be one of the novel and effective treatment modes of regional radiochemotherapy.