论文总字数：20728字

摘 要

目的：恶性肿瘤是当今影响人类健康、威胁人类生命的主要疾病之一。癌症的早期诊断与治疗是减少癌症死亡的重要手段，如果可以进行癌症的早期诊断，能够在疾病的早期阶段识别癌症并预测肿瘤行为，及时手术切除，之后的复发率很低，这样可以减少新的癌症病例的出现，减轻负担，并减少癌症造成的死亡人数。所以，癌症的早期诊断与治疗是治疗癌症的关键。

方法：首先我们通过EDC活化的方法将甲氧基-聚乙二醇-羧基（mPEG-COOH）修饰在聚乙烯亚胺表面，将马来酰亚胺-聚乙二醇-琥珀酰亚胺戊酸酯（MAL-PEG-SVA）作为中介，之后用于将两性离子通过该中介修饰在聚乙烯亚胺表面，进而修饰锝-99m的螯合剂二乙基三胺五乙酸（DTPA），随后修饰异硫氰酸荧光素（FI），包裹纳米金颗粒在其内部，标记锝-99m构建用于肿瘤SPECT/CT双模态成像的纳米造影剂。

结果：本实验结果表明，首先通过取代反应及缩合反应制备得到了pH敏感两性离子烷氧苯基酰磺酰胺（APAS），接着分别修饰13.28摩尔当量的mPEG-COOH，14.2摩尔当量的MAL-PEG-SVA，6.2摩尔当量的DTPA，4.8摩尔当量的FI，5.3摩尔当量制备得到的APAS在聚乙烯亚胺表面，并包裹纳米金颗粒在其内部，通过紫外可见吸收光谱（UV-Vis）证明构建的纳米复合材料在520 nm处有独特的表面等离子体共振峰（SPR），且该纳米复合材料水溶性良好。

结论：构建得到的pH敏感两性离子功能化的锝-99m标记聚乙烯亚胺包裹纳米金颗粒作为多模态成像造影剂有望极大的提高在肿瘤部位的富集量，通过电子计算机断层扫描（CT）及单光子发射计算机断层成像术（SPECT）实现肿瘤的精确高效诊断。

关键词：两性离子 锝-99m 聚乙烯亚胺 双模态成像 癌症诊断

The Study on SPECT/CT Dual Modal Contrast Agent pH-Sensitive Zwitterionic Functionalized Technetium-99m-Labeled Polyethylenimine Entrapped Gold Nanoparticle

Abstract

Objectives: Malignant tumors are one of the major diseases that affect human health and threaten human life today. Early diagnosis and treatment of cancer is an important means to reduce cancer deaths. Early diagnosis of cancer can identify cancer in the early stages of the disease and predict tumor behavior. Surgical resection can be performed immediately. The rate of recurrence after that is very low. This can reduce the number of new cancer cases, reduce the burden, and reduce cancer-related deaths. Number of people.Therefore, the early diagnosis and treatment of cancer is the key to the treatment of cancer.

Methods: Firstly, we modified methoxy-polyethylene glycol-carboxy (mPEG-COOH) on the surface of polyethyleneimine by means of EDC activation. The maleimide-polyethylene glycol-succinimidyl valerate (MAL-PEG-SVA) was used as an intermediate, and then was used to modify the zwitterion on the surface of polyethyleneimine through this intermediate, thereby modifying the chelating agent diethyltriaminepentaacetic acid (DTPA) of technetium-99m, then modifying the fluorescein isothiocyanate (FI), entrapping gold nanoparticle in its interior, labeled with technetium-99m as a nanocontrast agent for dual-modality SPECT/CT imaging of tumor.

Results: The results of this experiment indicate that pH-sensitive zwitterionic alkoxyphenyl sulfonamide (APAS) was first prepared by substitution reaction and condensation reaction, followed by modification 13.28 molar equivalents of mPEG-COOH and 14.2 molar equivalents of MAL-PEG-SVA, 6.2 molar equivalents of DTPA, 4.8 molar equivalents of FI, 5.3 molar equivalents of prepared APAS on the surface of polyethyleneimine respectively, then entrapping gold nanoparticle inside, and the constructed nanoparticle was confirmed by Ultra Violet-Visible absorption spectroscopy (UV-Vis). The composite materials have a unique surface plasmon resonance peak (SPR) at 520 nm, and the nanocomposites have good water solubility.

Conclusions: The constructed pH-sensitive zwitterionic functionalized technetium-99m-labeled polyethyleneimine-entrapped gold nanoparticles as multimodal imaging contrast agents are expected to greatly increase their accumulation at the tumor site, through Single Photon Emission Computed Tomography (SPECT) and Computed Tomography

(CT) to achieve accurate and efficient diagnosis of tumors.

Key words: Zwitterion; Technetium-99m; Polyethyleneimine; Dual modal imaging; Cancer diagnosis

目录

摘要 I

Abstract II

第一章 文献综述 1

1.1 癌症的现状 1

1.2 癌症的治疗现状和趋势 1

1.3 癌症的早期诊断 2

1.3.1分子影像技术 2

1.3.2 聚乙烯亚胺 3

1.3.3 肿瘤酸性环境 5

1.3.4 pH敏感两性离子 6

1.4 本课题的主要内容和研究意义 6

1.4.1 本论文主要内容 6

1.4.2 本论文的研究意义 7

第二章 实验方法 8

2.1 实验仪器 8

2.2 实验试剂 8

2.3 实验方法 9

2.4 材料的合成 10

2.4.1 APAS的合成 10

2.4.2 PEI.NH₂-mPEG 的合成 11

2.4.3 PEI.NH₂-(PEG-MAL)-(mPEG)的合成 11

2.4.4 PEI.NH₂-FI-DTPA-(PEG-MAL)-(mPEG)的制备 11

2.4.5 {(Au⁰)₂₀₀-PEI.NHAc-FI-DTPA-(PEG-APAS)-(mPEG)}PENPs的制备 12

2.5 材料的表征 12

2.5.1 氢核磁共振（¹H NMR）测试 12

2.5.2 紫外可见吸收光谱（UV-Vis）测试 12

第三章 结果与讨论 12

3.1 ¹H NMR及质谱测试 13

3.2 紫外可见吸收光谱分析 15

第四章 结论与展望 16

4.1 结论 17

4.2 课题研究展望 17

参考文献 17

致谢 21

请支付后下载全文，论文总字数：20728字