前哨淋巴結造影劑即時製備之相關研究

Studies of On-site Radiopharmaceutical Preparation for Sentinel Lymph Node Scintigraphy

王昱豐(Yuh-Feng Wang)

指導教授 ： 鍾美英

高雄醫學大學/藥學院/藥學研究所/博士(2011年)

https://doi.org/10.6832/KMU.2011.00001

摘要

前哨淋巴結造影是目前臨床上使用於乳癌或其他類似癌症在手術治療前規劃時相當重要的檢測依據。放射性同位素鎝-99m 標化人體血清白蛋白(Tc-99m Human Serum Albumin; Tc-99m HSA) 是進行此前哨淋巴結造影時相當良好的放射性製劑。然而，目前的臨床使用上卻遭遇幾個主要的問題。首先是製劑的來源：近年來，由於各種血液的傳染病盛行，血清製品的安全性一直是個相當難以克服的課題，事實上，目前對於Tc-99m HSA製劑之進口也相當之困難。再者，進行前哨淋巴結造影時需要直接由皮下注射放射性製劑，局部劇痛常是患者的主要抱怨，臨床上常使用局部麻醉藥品塗抹或直接加入藥劑中進行注射，然而混合配製Tc-99m HSA與局部麻醉劑Lidocaine Hydrochloride之穩定性卻需要評估。
本研究在此進行一系列以國造人體血清白蛋白標化Tc-99m之穩定性試驗，此試驗之主要精神即是世界衛生組織多年來所致力推動的“國血國用”原則。實驗中分別測定不同濃度比例下配製製劑之差別，並測試其穩定度及時間變化，以探討和比較製備Tc-99m HSA 過程中各種標化濃度對於提升穩定性的助益。接著，以此國血Tc-99m HSA製劑注入實驗動物的體內，分析在各種主要器官的分佈情形，比較與分析其結合或解離情形；以動物模式實際進行淋巴造影時，本製劑呈現出良好的淋巴攝取，並能在伽瑪攝影儀下標示出淋巴的位置。本研究並確認所有相關製備均通過熱源和無菌測試。
依本研究之結果發現，此放射性同位素標化之國血製劑可以適用於核醫學實驗室內之在地進行標化，並不需要特定之設備。然而，承前所述，進行前哨淋巴節造影時，局部的疼痛抑制相當的重要，所以，若需要以此製劑進行前哨淋巴節造影時，其與局部麻醉藥品lidocaine之混合配製是否能維持其穩定性則是臨床作業中相當重要的考量。本研究經系列實驗後發現，雖然並未呈現出明顯之統計意義（p>0.05），然而混合配製Tc-99m HSA與lidocaine之標化穩定性並不適當，隨時間其標化效率漸呈較差之趨勢。臨床上作業仍建議以局部塗抹之麻醉藥品並搭配顆粒大小過濾篩檢後之Tc-99m HSA為宜。

關鍵字

前哨淋巴結 ； 鎝-99m ； 人體血清白蛋白 ； 淋巴結造影

並列摘要

Identification of sentinel lymph nodes (SLN) via lymphoscintigraphy, the SLN mapping, has been accepted for pre-surgical evaluation for breast cancer and other types of solid tumors. Technetium-99m human serum albumin (Tc-99m HSA) is one of the radiopharmaceutical suitable for this procedure. However, there are some problems exist to limit their clinical application. Because of transfusion-induced infectious diseases, the safety of serum products is a serious concern. Moreover, a suitable commercial kit for Tc-99m HSA is not currently available in many countries. In addition, this examination usually causes extreme painful adverse reaction to patients. Therefore, pre-treatment with local anaesthesia or a mixture of lidocaine and radiopharmaceutical is needed. However, stability of the mixture is another related dilemma.
A series of on-site preparations of radiolabeled human serum albumin with domestic serum products were conducted. This concept is fit with the recommendation from World Health Organization that encouraged each country to use its native serum products. Different formulations were prepared and the labeling efficiency and stability were studied. Bio-distribution studies were performed and all the samples passed the pyrogenicity and sterility tests. Lymphoscintigraphy with our on-site prepared radio-product also showed good presentation of lymph node images. These data indicated that the preparation of Tc-99m HSA using domestic serum products is useful and potentially applicable at clinical settings.
When the procedure of SLN mapping was conducted, pain-relief is a practical issue. The stability of the pre-mixture of lidocaine with Tc-99m HSA should be evaluated. However, serial results showed that the radiochemical purity of this mixture was not so stable. Though it is not significant (p>0.05), a tendency of decline in radiochemical purity was presented. External anesthesia followed by subcutaneous injection of a filtered Tc-99m HSA is appropriate for clinical application.

並列關鍵字

sentinel lymph nodes ； Technetium-99m ； human serum albumin ； lymphoscitigraphy

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