αvβ3 integrin是一種與腫瘤血管新生及腫瘤轉移相關的細胞黏著受器(cell adhesion receptor)。由於αvβ3 integrin與具Arg-Gly-Asp(RGD)序列之胜肽具有高度的專一結合性，利用放射性標誌RGD胜肽可發展成為有效且具專一性的腫瘤造影劑。據文獻報導，迄今已有多種放射性核種標誌化合物被探討用於偵測αvβ3 integrin，進而作為腫瘤造影劑。鑑於99mTc具有優良的核子特性(Eγ=140.5 keV；t1/2=6 hr；可由99Mo-99mTc發生器取得經濟又方便)，以99mTc標誌RGD peptide，當具有臨床醫學應用的價值。
本研究旨在開發99mTc(I)-HYNIC-RGD藥物應用於腫瘤血管新生造影。參考過去文獻報導方法分別製備出NHS-HYNIC、HYNIC-RGD 耦合物與[99mTc(CO)3(OH2)3]+【Abrams et al. J Nucl Med 31 (1990) 2022和Su et al. Bioconjugate Chem 13 (2002) 561和Alberto et al. J Am Chem Soc 120 (1998) 7987】。以NHS-HYNIC與RGD作用製備成HYNIC-RGD耦合物。繼之以[99mTc(CO)3(OH2)3]+為前驅物於pH 7.4及室溫條件下進行標誌HYNIC-RGD得99mTc(I)-HYNIC-RGD。在本研究製備所得之99mTc(I)-HYNIC-RGD 溶液，利用放射化學分析方法包括薄層層析法(TLC)、電泳動分析(EP)和高效能液相層析(HPLC)測定標誌效率。
根據實驗結果得知99mTc(CO)3+標誌於HYNIC-RGD標誌產率可達60%以上，顯見99mTc(I)-HYNIC-RGD藥物製備之可行性。而活體的動物實驗目前仍在進行當中，尚無具體的結果。

The αvβ3 integrin is an important cell adhesion receptor involved in tumor-induced angiogenesis and tumor metastasis. The high binding specificity to αvβ3 integrins of peptides containing Arg-Gly-Asp (RGD) residue suggests that the radiolabeled RGD peptides be useful as tumor specific imaging agents. Recently, several radionuclides were used to detect αvβ3 integrins and were suitable for noninvasive determination of tumor status, therapy monitoring and possibility of tumor metastasis. Since 99mTc is characteristic of excellent radionuclide with a high-resolution 140.5 keV γ, a half-life 6 h, economically and conveniently available from 99Mo-99mTc generator and extensively used in nuclear medicine, it will be significant to develop 99mTc labeled RGD peptide for clinical use in nuclear medicine.
Synthesis of NHS-HYNIC, conjugation of RGD peptide with NHS-HYNIC and preparation of [99mTc(CO)3(OH2)3]+ were carried out respectively according to the previous reports [Abrams et al. J Nucl Med 31(1990) 2022, Su et al. Bioconjugate Chem 13(2002) 561 and Alberto et al. J Am Chem Soc 120(1998) 7987]. RGD peptide was labeled with [99mTc(CO)3(OH2)3]+ via hydrazinonicotinamide as a bifunctional chelator. 99mTc(I)-HYNIC-RGD was prepared by mixing the [99mTc(CO)3(OH2)3]+ solution with HYNIC-RGD in PBS buffer at room temperature. Radiochemical characterization for 99mTc(I)-HYNIC-RGD were conducted by thin layer chromatography, electrophoresis, and HPLC.
According to the results, the radiochemical purity for 99mTc(I)- HYNIC-RGD was around 60%. The synthesis and labeling work for 99mTc(I)-HYNIC-RGD has been established in this study. Furthermore in vitro and in vivo tests for 99mTc(I)-HYNIC-RGD for tumor angiogenesis imaging study are underway.

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