開發奈米磁振造影與核醫雙功能造影劑

Abstract

目前利用liposomes來包覆的藥物和lipid-based iron oxide nanoparticle 作為 contrast-enhanced MRI和molecular imaging 造影劑(稱為magnetoliposome或稱為 magnetic- fluid-loaded liposomes)已成為奈米醫學藥物 (nanomedicine) 重要的一 環，它的最大優點是增加在體內循環時間，使藥物更能有效傳送到病灶，及減少傳 送途中，正常細胞之吸收藥物量。 利用PEG-lipid 包覆iron oxide particle 可分為二類 (1).bilayer on nanoparticles：iron oxide particle 位於liposome 之中心，所用之iron oxide particle 為水溶性，如用PEG 或dextran 包覆之magnetite。 (2).nanoparticle-containing micelles：奈米氧化鐵被phospholipid 單層包圍在中間。 所用之iron oxide particle 為脂溶性，如用oleic acid、dodecylamine 或lauric acid 包覆之magnetite。 首先本計劃將配合核能研究所同位素應用組以發展成熟之PEG-lipid 加工技 術與放射性同位素標記技術，magnetoliposomes/radiomagnetoliposomes之製備策略 用親水性或疏水性之奈米氧化鐵粒子，製備成magnetoliposomes或micellular iron oxide。而在PEG-lipid形成thin film後，加入奈米氧化鐵粒子時，亦同時加入放射 性同位素(由同位素應用組提供，如Tc-99m或In-111)，就有機會製備成，使其成 為具奈米磁振造影與核醫雙功能造影劑。並作產品性質測定：Z-average diameter 、zeta-potential、MRI之R1(T1)和R2(T2)、TEM。radiomagnetoliposome產 品：radio-instant chromatography(labeling efficiency)等初步篩選與鑑定。

Preparation of magnetoliposome and radiomagnetoliposome: a potential dual modality imaging agent useful for MRI contrast agent and/or SPECT imaging agent Lipid-based colloidal aggregates, such as liposomes, micelles, microemulsions, have been used extensively in recent decades as drug carriers to to improve pharmacokinetic properties or the bioavailability of the drug or to deliver hydrophobic drugs. Iron oxide nanoparticles are of considerable interest in nanoscience and nanotechnology because of their nanoscale dimensions, nontoxic nature, and superior magnetic properties. Potential applications of iron oxide nanoparticles in biomedical sciences have been extensively reviewed. Both magnetic resonance imaging (MRI) with contrast agent nuclear imaging with tagging radioisotope are the most versatile imaging methods available in both clinical and research settings. MRI has good spatial resolution but inherently low sensitivity. On the other hand SPECT has high sensitivity but the definition of anatomy is poor. It is worth to prepare a dual modality imaging agent for both MRI contrast agent and/or SPECT imaging agent useful for molecular imaging. We will use superparamagnetic iron oxide (SPIO) nanoparticles as MRI T2 contrast agent, Tc-99m radioactive element for SPECT, and PEG-lipid for liposomes. Firstly, the hydrophilic and/or hydrophobic SPIO nanoparticles will be synthesized via coating with chitosan and its derivatives. We will use Co-60 γ-ray irradiation on solid chitosan not only to lower its molecular weight but also to introduce carbonyl groups that may favour SPIO stabilization. Then with the corporation with the division of isotopes Applications for their expertise of lipid technology as well as radioactive labeling technique, both magnetoliposome and radiomagnetoliposomes will be attempted to synthesized in the Division. Their features will be characterized by z-average diameter, zeta potential, MRI parameters of r1, r2, and radio-instant thin layer chromatography.