三羰基鎝99m(I)標誌人體血清蛋白奈米粒子之製備

Preparation of Tricarbonyl 99mTc(I) Labeled Human Serum Albumin Nanoparticles

張修瑀(Hsiu-Yu Chang)

指導教授 ： 羅建苗

國立清華大學/原子科學院/核子工程與科學研究所/碩士(2012年)

摘要

本研究旨在製備人體血清蛋白（Human serum albumin，簡稱HSA)奈米級粒子（Nanoparticles，簡稱NPs）。 藉實質固態腫瘤的高通透性和滯留效應，奈米粒子可傳送至腫瘤。本研究將此HSA-NPs予以標誌放射性同位素核種 99mTc，期發展在臨床上做腫瘤造影診斷之用途。
方法：首先以反溶解技術製得 HSA-NPs ，接著將99mTc　以99mTc(I)-tricarbonyl　的離子態標誌，得99mTc標誌產物，簡稱為 99mTc(I)-tricarbonyl-HSA-NPs。接著藉由粒徑測試和體外穩定度試驗評估此試劑的生物穩定性。
結果：在粒徑測試中，此奈米粒子於製備後至少可保存至兩個月都不會有明顯的聚集現象，粒徑分佈維持在217.9 ± 5.2 nm。在標誌 99mTc後，在室溫放置48小時後，粒徑分佈為 233.3 ± 7.6 nm； 在37°C放置48小時後，粒徑分佈為 234.7 ± 8.2 nm。在體外穩定度試驗證實無論在生理食鹽水或是大鼠血清中，於48小時後99mTc(I)-tricarbonyl-HSA-NPs仍維持約 90% 的放射化學純度。
結論： 本研究已完成人體血清蛋白奈米粒子製備、 99mTc標誌、粒徑測試以及體外穩定度試驗。未來可進行動物實驗加以測試此奈米粒子在腫瘤造影診斷之效用。

關鍵字

人體血清蛋白 ； 奈米粒子 ； 粒徑分佈 ； 放射性標誌 ； 三羰基鎝99m(I)

並列摘要

This study has attempted to prepare human serum albumin (HSA) nanoparticles (NPs) for targeting solid tumor cells via the enhanced permeability and retention (EPR) effect. HSA-NPs was labeled with 99mTc using the 99mTc(I)-tricarbonyl ion, [99mTc(CO)3(OH2)3]+ as a precursor to prepare as a radiotracer for clinically imaging use.
Methods: HSA-NPs were produced by a desolvation technique. [99mTc(CO)3(OH2)3]+ was prepared and subjected to directly label HSA-NPs. The resulted 99mTc(I)-tricarbonyl labeled HSA-NPs, abbreviated as 99mTc(I)-tricarbonyl-HSA-NPs, was measured for its particle size distribution and in vitro stability.
Results: According to DLS analysis, the HSA-NPs prepared could be preserved without aggregation and kept at the size distribution as 217.9 ± 5.2 nm. After being radiolabeled, the particles were found with size distribution at 233.3 ± 7.6 nm at room temperature and at 234.7 ± 8.2 nm at 37°C after storage for 48 h. The radiochemical purity of 99mTc(I)-tricarbonyl-HSA-NPs could maintain at 90% after incubation either in normal saline and in rat plasma for 48 h.
Conclusion: HSA-NPs was successfully prepared in nanometer scale and could be readily labeled with 99mTc(I)-tricarbonyl ion. The 99mTc labeled HSA-NPs was stable during incubation either in normal saline and in plasma.

並列關鍵字

human serum albumin ； nanoparticles ； particle size distribution ； radiolabeling ； 99mTc(I)-tricarbonyl

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