90Y and 177Lu Labeling of a DOTA-Conjugated Vitronectin Receptor Antagonist Useful for Tumor Therapy
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- 作者：Shuang Liu ; Eric Cheung ; Marisa C. Ziegler ; Milind Rajopadhye ; and D. Scott Edwards
- 刊名：Bioconjugate Chemistry
- 出版年：2001
- 出版时间：July 2001
- 年：2001
- 卷：12
- 期：4
- 页码：559 - 568
- 全文大小：206K
- 年卷期：v.12,no.4(July 2001)
- ISSN：1520-4812
文摘
The 90Y and 177Lu complexes (RP697 and RP688, respectively) of a DOTA-conjugated vitronectinreceptor antagonist (SU015: 2-(1,4,7,10-tetraaza-4,7,10-tris(carboxymethyl)-1-cyclododecyl)acetyl-Glu(cyclo{Lys-Arg-Gly-Asp-D-Phe})-cyclo{Lys-Arg-Gly-Asp-D-Phe}) were prepared by reacting SU015 withthe radiometal chloride in ammonium acetate buffer (pH > 7.2) in the presence of an antioxidant(sodium gentisate, GA). Through a series of radiolabeling experiments, it was found that there aremany factors influencing the rate of 90Y chelation and the radiolabeling efficiency of SU015. Theseinclude the purity of SU015, the pH, reaction temperature, and heating time, as well as the presenceof trace metal contaminants, such as Ca2+, Fe3+, and Zn2+. The chelation of 90Y by SU015 is slow, sothat heating at elevated temperatures (50-100 
C) is needed to complete the 90Y-labeling. The rateof 90Y chelation is also dependent on the pH of the reaction mixture. Under optimized radiolabelingconditions (pH 7.2-7.8 and heating at 50-100 C for 5-10 min), the minimum amount of SU015required to achieve 95% RCP for RP697 is ~25 
g for 20 mCi of 90YCl3 corresponding to a SU015:90Yratio of ~30:1.
C) is needed to complete the 90Y-labeling. The rateof 90Y chelation is also dependent on the pH of the reaction mixture. Under optimized radiolabelingconditions (pH 7.2-7.8 and heating at 50-100 C for 5-10 min), the minimum amount of SU015required to achieve 95% RCP for RP697 is ~25 g for 20 mCi of 90YCl3 corresponding to a SU015:90Yratio of ~30:1.