鎝99m(I)標誌octreotide胜肽作為胰臟癌細胞造影劑之研究

Study on 99mTc(I) Labeled Octreotide for Pancreas Tumor Imaging

張心怡(Hsin-Yi Chang)

指導教授 ： 羅建苗 ； 李德偉

國立清華大學/原子科學院/原子科學系/碩士(2006年)

摘要

具有八個胺基酸的環型胜肽octreotide，是一種體抑素類似物，對體抑素受體具有高度親和力。本研究旨在發展99mTc(I)-HYNIC-octreotide為一種有效的體抑素受體造影劑。本研究參考核能研究所的方法，以固相胜肽合成法製備HYNIC-octreotide。並參考文獻方法合成HYNIC及[99mTc(CO)3(OH2)3]+。以[99mTc(CO)3(OH2)3]+為前驅物，於75℃及中性條件下進行標誌HYNIC-octreotide得99mTc(I)-HYNIC-octreotide。根據實驗結果得知[99mTc(CO)3(OH2)3]+標誌於HYNIC-octreotide標誌產率可達90%以上。HYNIC-octreotide在體抑素受體競爭實驗中，有效地抑制125I-Tyr11-Somatostatin的結合，證實HYNIC-octreotide具有對體抑素受體的結合能力。經由活體動物實驗，注入99mTc(I)-HYNIC-octreotide於種有AR42J腫瘤之SCID小鼠，其腫瘤位置顯現清楚並且持續累積的影像，證實99mTc(I)-HYNIC-octreotide對具體抑素受體之腫瘤有造影之潛力。

關鍵字

鎝99m

並列摘要

Octreotide, a cyclopeptide with eight amino acids, is a somatostatin analog with the affinity to somatostatin receptors. The aim of the study is to develop 99mTc(I)-HYNIC-octreotide as radiopharmaceutical for somatostatin receptor scintigraphy. HYNIC-octreotide is synthesizd by the method of solid-phase peptide synthesis with disulfide bonding developed by Institute of Nuclear Energy Research. HYNIC and [99mTc(CO)3(OH2)3]+ were prepared respectively according to the previous reports. Octreotide was labeled with [99mTc(CO)3(OH2)3]+ via HYNIC as a bifunctional chelator. 99mTc(I)-HYNIC-octreotide was prepared by mixing the [99mTc(CO)3(OH2)3]+ solution with HYNIC-octreotide in saline at 75℃. According to the results, the radiochemical purity for 99mTc(I)-HYNIC-octreotide was greater than 90%. The labeling technique for 99mTc(I)-HYNIC-octreotide has been successfully established in this study. The HYNIC-octreotide efficiently inhibited the binding ability of 125I-Tyr11-somatostatin with somatostatin receptor regarding to the retention of its receptor-binding affinity. In the animal model, 99mTc(I)-HYNIC-octreotide was uptaken by the pancreas tumor cells (AR42J) implanted into the SCID mice, and the result showed by showing a clear image for the tumor. These results demonstrated that 99mTc(I)-HYNIC-octreotide is potential for imaging pancreas tumors via somatostatin receptors .

並列關鍵字

Tc-99m ； octreotide

參考文獻

1. Saha G. B., Fundamentals of Nuclear Pharmacy, 4th ed. Springer. 1997.

2. Krenning EP, Kwekkeboom DJ, Valkema R, Pauwels S, Kvols LK, and Jong MD. Peptide receptor radionuclide therapy. Ann N Y Acad Sci, 1014: 234-245, 2004.

3. Hom RK and Katzenellenbogen JA. Techetium-99m labeled receptor-specific small-molecule radiopharmaceticals: recent developments and encouraging results. Nucl Med Biol, 24: 485-498, 1997.

4. Schwochau K. Technetium radiopharmecuticals-fundamentals, synthesis, structure, and development. Angew Chem Int Edit Engl, 33: 2258-2267, 1994.

5. Jurisson SS and Lydon JD. Potential technetium small molecule radiopharmaceuticals. Chem Rev, 99: 2205-2218, 1999.