鎝—99m—HMPAO添加穩定劑之研究

Study of 99mTc-HMPAO with Stabilizers

王世楨(Shyh-Jen Wang) ； 蔡世傳(Shih-Chuan Tsai) ； 林萬鈺(Wan-Yu Lin) ； 高嘉鴻(Chia-Hung Kao) ； 吳美智(Mei-Chih Wu) ； 魏孝萍(Shiaw-Pyng Wey) ； 沈立漢(Lie-Hang Shen) ； 蔡瑞燦(Zei-Tsan Tsai) ； 丁幹(Gann Ting)

《核子醫學雜誌》 12卷2期 (1999/06) Pp. 77-83

摘要

前言：鎝-99m-HMPAO爲核醫腦血流造影診斷的重要核醫藥物，由於鎝-99m-HMPAO的不安定性限制本藥必須在標幟後三十分鐘內使用。本研究目的為評估次甲藍-磷酸鈉及氯化亞鈷溶液對核研所HMPAO凍晶小瓶製備之鉻-99m-HMPAO之穩定效果，並與英國Amersham公司Ceretec kit比較。材料與方法：本研究共使用三十隻紐西蘭公兔並分為五組，第一組注射未添加穩定劑的鎝-99m-HMPAO。第二組注射添加次甲藍-磷酸鈉溶液的鎝-99m-HMPAO，並於標幟後十分鐘注射。第三組注射添加氯化亞鈷水溶液的鎝-99m-HMPAO，並於標幟後十分鐘注射。第四組注射添加次甲藍-磷酸鈉溶液的鎝-99m-HMPAO，並於標幟後四小時注射。第五組注射添加氯化亞鈷水溶液的鎝-99m-HMPAO，並於標幟後四小時注射。各組並分為二小組，分別使用核研所產製之核研宏寶鎝及英國Amersham公司Ceretec凍晶小瓶製備之鎝-99m-HMPAO。每隻動物於注射後30、60、120、180、300分鐘分別進行核子醫學全身造影並以電腦計算出腦部攝取活性佔全身攝取活性之比率。結果：不論核研宏寶鎝或Amersham之Ceretec kit製備之鎝-99m-HMPAO加入次甲藍-磷酸鈉或氯化亞鈷溶液穩定劑均不會改變鎝-99m-HMPAO原來的放射化學純度，但會顯著延緩鎝-99m-HMPAO的分解；標幟6小時放射化學純度仍可維持在80％以上。比較次甲藍-磷酸鈉及氯化亞鈷溶液兩種穩定劑對搭-99m-HMPAO之放射化學穩定效果，並無明顯差異。加入次甲藍-磷酸鈉溶液或氯化亞鈷水溶液穩定劑，初期的大白兔腦部活性分佈以至後續的緩慢清除，與未添加穩定劑者沒有明顯差別，證實穩定劑的添加不會改變鎝-99m-HMPAO在腦組織之正常動態分佈。添加穩定劑4小時後注射之大白兔腦組織之正常動態分佈與標幟後10分鐘靜脈注射者差異有限。結論：研究結果顯示由核研所及Amersham生產之HMPAO凍晶小瓶製備之鎝-99m-HMPAO添加穩定劑（次甲藍或氯化亞鈷）後，均能延長臨床造影使用之放射化學穩定性達6小時，將可大幅提昇核醫臨床使用之方便性。

關鍵字

鎝—99m—HMPAO ； 穩定劑 ； 氯化亞鈷 ； 次甲藍

並列摘要

Background:99mTc-HMPAO is an important radiopharmaceutical for clinical study of regional cerebral flow in nuclear medicine. The inherent instability of 99mTc-HMPAO limits that the tracer should be used within 30 minutes after preparation. The aim of this study is to evaluate the stabilizing effect of methylene blue-sodium phosphate and cobaltous chloride on 99mTc-HMPAO in the reconstitution solution of commercial kit prepared from the Institute of Nuclear Energy Research(INER),and compared with the Ceretec kit from Amersham International plc. Methods: Totally 30 New Zealand male rabbits were involved in this study. Six rabbits in each of five groups were intravenously injected with 99mTc-HMPAO in following conditions: Group 1 injected tracer without stabilizer at 10 min after preparation; Group 2 injected tracer with methylene blue-sodium phosphate at 10 min after preparation;Group3 injected tracer with cobaltous chloride at 10 min after preparation; Group 4 injected tracer with methylene blue-sodium phosphate at 4 hours after preparation; Group 5 injected tracer with cobaltous chloride at 4 hours after preparation. In each group, three rabbits were injected with 99mTc-HMPAO reconstituted from INER kits, the other three were injected with tracer prepared from Ceretec kits. Whole-body scan for each animal performed at 30,60,120,180 and 360 min post-injection. The brain uptake of each rabbit at each time point was calculated for comparison. Results: The decomposition of lipophilic 99mTc-HMPAO significantly slowed by addition of methylene blue-sodium phosphate or cobaltous chloride solution to the reconstitution of either INER HMPAO kit or Amersham Ceretec kit, while the initial radiochemical purity of 99mTc-HMPAO seemed unchanged with either stabilizer. Over 80% radiochemical purity was observed in the stabilized reconstitution solution 6 hours after preparation. There was no significant difference of stabilizing power to 99mTc-HMPAO between methylene blue-sodium phosphate and cobaltous chloride solutions. The kinetic distribution of stabilized 99mTc-HMPAO in the brain of rabbit was unchanged from that with unstabilized 99mTc-HMPAO administration. Limited lower brain distribution, shown particularly at 30 min following injection with stabilized 99mTc-HMPAO 4 hours after preparation, might be a consequence of slight docomposition of lipophilic tracer even stabilizers applied. Conclusion: We conclude that the 99mTc-HMPAO prepared either from INER HMPAO kit or from Amersham Cereteckit, and stabilized either with methylene blue-sodium phosphate or with cobaltous chloride solution, can be provided with clinically acceptable radiochemical stability for up to 6 hours, which should widely improve the clinical use of99mTc-HMPAO in nuclear medicine.

並列關鍵字

99mTc-HMPAO ； stabilizer ； cobaltous chloride ； methylene blue