分子成像技術 (Molecular imaging)，例如正電子發射斷層掃描 (Positron Emission Tomography) 成像，是一種無創檢測癌症和其他人類疾病的強大工具。雙模組探針結合輻射成像和近紅外螢光成像，用於術前成像和即時手術指導，目的在於加強癌症患者的治療。考慮到當前的雙模組探針的合成方法涉及多步驟和繁瑣的合成，我們試圖開發一系列基於多功能單附著點 (Multifunctional single-attachment-point)方法的雙模態試劑，用於標記生物分子。利用一種新的生物正交反應，2- cyanobenzothiazole (CBT)/ 1,2-aminothiol 點擊反應，我們可將顯像劑和目標分子進行的區域選擇性的標誌。在此，我們描述了結合 DOTA（放射性金屬螯合劑）、cypate (螢光分子) 和 CBT 的雙模態試劑的設計和合成。此外，我們通過用我們合成的顯像劑標記 PSMA-617（一種已知的前列腺特異性膜抗原配體）證明了這種方法的可行性。我們設想此處開發的化學和顯像劑可能對核醫學的進步產生影響。

Molecular imaging, such as positron emission tomography (PET) imaging, is a powerful tool for the non-invasively detection of cancers and other human diseases. Dual-modality probes combine radiation imaging and near-infrared fluorescence imaging for pre-operative imaging and real-time surgical guidance, aiming to enhance cancer patient treatment. Considering current methods for dual-modality probe involves multi-step and tedious synthesis, we sought to develop a new series of dual-modality agents based on multifunctional single-attachment-point (MSAP) approach for labeling biomolecules. A novel bioorthogonal reaction, 2-cyanobenzothiazole (CBT)/1,2- aminothiol click reaction, was adopted for the regioselective conjugation between the imaging agents and targeted molecules. Herein, we described the design and synthesis of the dual-modality agents with the combination of DOTA (radiometal chelator), cypate (FL), and CBT moiety. In addition, we demonstrated the feasibility of this approach by labeling the PSMA-617, a known prostate-specific membrane antigen ligand, with our synthesized imaging agents. We envision the chemistry and imaging agents developed herein can have implications for the advancement of nuclear medicine.

中文摘要 I
ABSTRACT III
目錄 V
圖目錄 VII
一、文獻討論 1
1.1. 分子影像 1
1.2. 核子成像 2
1.2.1. 正電子放射斷層掃描 2
1.2.2. 單光子電腦斷層掃描 2
1.3. 光學成像 3
1.4. 紅外光螢光探針 4
1.5. 雙模組成像探針 5
1.6. 2-氰基苯並噻唑 / 1,2-胺基硫醇點擊反應 6
1.7. 多功能單連接點 (MULTIFUNCTIONAL SINGLE-ATTACHMENT-POINT, MSAP) 7
1.8. 前列腺特定膜抗原 (PROSTATE-SPECIFIC MEMBRANE ANTIGEN, PSMA) 8
二、研究動機 11
三、藥品 13
四、儀器 15
五、實驗合成 17
1.1. CBT (8) 合成17
1.2. CBT-DOTA-CY5 液相合成 20
1.3. CBT-DOTA-CY5 固相合成 24
1.4. CBT-DOTA-CY7 合成 26
1.5. 18和25 螢光光譜分析 27
1.6. 18和CYSTINE進行點擊化學的測試 28
1.7. PSMA-617-CYS 液相合成 30
1.8. PSMA-617-CYS 固相合成 35
1.9. 雙模組試劑與PSMA 點擊化學合成 38
1.10. 雙模組試劑標誌金屬之合成 39
六、結果討論 41
七、實驗方法 43
八、參考文獻 61
九、光譜 65

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