양전자 방출핵종 68Ga을 이용한 NOTA와 DOTA의 표지 및 시험관내 특성 연구 (Radiolabeling of NOTA and DOTA with Positron Emitting 68Ga and Investigation of In Vitro Properties) |
Author |
정재민, 김영주, 이윤상, 이동수, 정준기, 이명철, |
Jae Min Jeong, Ph.D., Young Ju Kim, B.S., Yun-Sang Lee, Ph.D., Dong Soo Lee, M.D.,June-Key Chung, M.D., and Myung Chul Lee, M.D. |
Affiliation |
서울대학교 의과대학 핵의학교실 Department of Nuclear Medicine, Seoul National University College of Medicine, Seoul, Korea. |
Abstract |
Purpose: We established radiolabeling conditions of NOTA and DOTA with a generator-produced PET radionuclide 68Ga and studied in vitro characteristics such as stability, serum protein binding, octanol/water distribution, and interference with other metal ions. Materials and Methods: Various concentrations of NOTA․3HCl and DOTA․4HCl were labeled with 1 mL 68GaCl3 (0.18~5.75 mCi in 0.1 M HCl) in various pH. NOTA․3HCl (0.373 mM) was labeled with 68GaCl3 (0.183~0.232 mCi/0.1 M HCl 1.0 mL) in the presense of CuCl2, FeCl2, InCl3, FeCl3, GaCl3, MgCl2 or CaCl2 (0~6.07 mM) at room temperature. The labeling efficiencies of 68Ga-NOTA and 68Ga-DOTA were checked by ITLC-SG using acetone or saline as mobile phase. Stabilities, protein bindings, and octanol distribution coefficients of the labeled compounds also were investigated. Results: 68Ga-NOTA and 68Ga-DOTA were labeled optimally at pH 6.5 and pH 3.5, respectively, and the chelates were stable for 4 hr either in the reaction mixture at room temperature or in the human serum at 37°C. NOTA was labeled at room temperature while DOTA required heating for labeling. 68Ga-NOTA labeling efficiency was reduced by CuCl2, FeCl2, InCl2, FeCl3 or GaCl3, however, was not influenced by MgCl2 or CaCl2. The protein binding was low (2.04~3.32%). Log P value of 68Ga-NOTA was -3.07 indicating high hydrophilicity. Conclusion: We found that NOTA is a better bifunctional chelating agent than DOTA for 68Ga labeling. Although, 68Ga-NOTA labeling is interfered by various metal ions, it shows high stability and low serum protein binding. (Nucl Med Mol Imaging 2009;43(4):330-336)
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Keyword |
Ga-68, gallium, protein binding, bifunctional chelating agent, generator, NOTA, DOTA |
Full text Article |
11_정재민.pdf
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