Abstract
摘要:分子及活體細胞追蹤造影技術在臨床診斷與基礎醫學研究上扮演著日益重要的角色。本研究目的
為發展生醫分子及活體細胞追蹤之磁振造影技術,並研究其在早期偵測並評估肺癌細胞小鼠模式之腫
瘤血管新生型態功能及其轉移。主要內容為發展動態顯影磁振造影之血管新生評估技術、開發對細胞
分子表現特異性鑑別之奈米磁振顯影劑、並且利用高溫超導射頻線圈及平行影像重建法來達到高訊雜
比及高效率之磁振造影技術,用來研究肺癌細胞與肺臟轉移小鼠模式。結合上述技術之開發則可更進
一步提供病灶分子病理資訊並設計多功能甚或智慧型藥劑,使醫師得以即時知道用藥之效能與投遞分
布情形以最佳化治療策略。
此計畫針對肺癌之疾病模式作為主要之疾病研究標的,其主因為肺癌之臨床特徵為不易早期診
斷,並常早期發生轉移,尤其是肺腺癌更常在疾病發現初期,即有遠處轉移之現象,並且常有手術後
復發之情況。就目前的治療成效,非小細胞肺癌對放射線治療及化學治療之反應也較差。因此研究發
展早期診斷肺癌、早期偵測肺癌轉移、評估腫瘤血管新生能力以及監測肺癌治療反應之新方法,即成
為刻不容緩之課題。於此,本團隊已建立VEGF(vascular permeability factors)與EGFR 超表現或低表
現之鼠肺癌活體模型之標準化誘導程序,可快速以正位手術移植法重現,將作為本研究標的。
於子計畫二針對細胞分子表現特異性鑑別之奈米磁振顯影劑的發展平台部份,可藉由測試修改奈
米粒徑及表面化學以改良並強化其顯影效果並合成可控制均勻大小之正(胺基)或負電荷(梭基)表面之
氧化鐵奈米粒作為負顯影劑之核心部分;根據過去的文獻報導,EFGR(Epidermal growth factor receptor)
為一腫瘤生長激素表面受器,其功能可被抗EGFR 抗體抑制(本團隊已可自融合瘤量產並純化此抗
體),因此並進一步連結抗腫瘤特異性表面抗原之單株抗體,如EGFR 或其重組抗體,以作為融合標
的投遞之導向器及攻擊武器於一體之雙功製劑。
為求有較高效率之對比試劑,於此計畫中亦同時發展新型態之釓奈米材料作為正向對比顯影,如
此可增加多功能製劑的奈米載體,並作為發展新型顯影藥物之技術平台。
Abstract: Molecular and cell specific imaging play increasingly important roles in both clinical diagnosis and fundamental biomedical researches. In this study, we aim to develop a platform of nanocontrast agents and molecular MR imaging system that specifically recognizes cancer cells and exerts its therapeutic efficacy while enables real-time tracking of the drug distribution. This kind of system will provide not only valuable molecular pathological information but also real-time therapeutic efficacy evaluation for personalized healthcare treatment strategy.
Among various disease models, lung cancer is one of the most common causes of cancer-related death
in Taiwan (top 2nd) as well as other industrialized nations. The prognosis of lung cancer is poor as compared with other malignancies. Therefore, the research for early diagnosis, early detection of metastasis, and tumor-associated angiogenesis process, and assessment of therapeutic response become more and more important for lung cancer diagnosis and treatment. In this study, pulmonary tumor implantation animal models in mice with high and low VEGF (vascular permeability factors) and EGFR expression lung cancer cell carcinoma model were established by our team and will be used through the whole three years.
In subproject 2, there are evidences of non-invasive measurement of vascular permeability characteristics and apoptosis of tumor before the change of tumor size by using MRI with the information from apparent diffusion coefficient (ADC) and superparamagnetic iron oxide (SPIO) particles. For specifically recognized cancer cells, we have previously developed synthesis of iron oxide nanoparticles with excellent stability, biocompatibility, and interface for additional biochemical modifications. In this project, we will improve the synthesis and modifications of iron oxide nanoparticle to achieve better contrast and targeting effect. Furthermore, for combined molecular expression specific cancer targeting and therapy, bioconjugation of nanoparticles with anti-EGFR(Epidermal growth factor receptor) monoclonal antibody or specific recombinant ligand peptides will be performed, and the materials will be evaluated whether or not an increased signal contrast and hence high detection rate could be achieved for early detection of metastatic lesions.
Furthermore, we also developed Gd-based nanocontrast agents for MR positive contrast agent using in
this year, and this Gd-based nanocontrast agent would be as platform for nanomedicine and photothermal therapy applications.
Keyword(s)
分子影像
非侵入性醫療
肺癌
氧化鐵奈米粒子
奈米醫藥
Molecular imaging
Non-invasive
Lung cancer
Iron oxide nanoparticle
Anti-EGFR antibody
Gd-based