Click Chemistry for 18F-Labeling of RGD Peptides and microPET Imaging of Tumor Integrin αvβ3 Expression

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• 作者：Zi-Bo Li ; Zhanhong Wu ; Kai Chen ; Frederick T. Chin ; Xiaoyuan Chen
• 刊名：Bioconjugate Chemistry
• 出版年：2007
• 出版时间：November 2007
• 年：2007
• 卷：18
• 期：6
• 页码：1987 - 1994
• 全文大小：691K
• 年卷期：v.18,no.6(November 2007)
• ISSN：1520-4812

文摘

The cell adhesion molecule integrin α_vβ₃ plays a key role in tumor angiogenesis and metastasis. A series of ¹⁸F-labeled RGD peptides have been developed for PET of integrin expression based on primary amine reactive prosthetic groups. In this study, we report the use of the Cu(I)-catalyzed Huisgen cycloaddition, also known as a click reaction, to label RGD peptides with ¹⁸F by forming 1,2,3-triazoles. Nucleophilic fluorination of a toluenesulfonic alkyne provided ¹⁸F-alkyne in high yield (nondecay-corrected yield: 65.0 ± 1.9%, starting from the azeotropically dried ¹⁸F-fluoride), which was then reacted with an RGD azide (nondecay-corrected yield: 52.0 ± 8.3% within 45 min including HPLC purification). The ¹⁸F-labeled peptide was subjected to microPET studies in murine xenograft models. Murine microPET experiments showed good tumor uptake (2.1 ± 0.4%ID/g at 1 h postinjection (p.i.)) with rapid renal and hepatic clearance of ¹⁸F-fluoro-PEG-triazoles-RGD₂ (¹⁸F-FPTA-RGD2) in a subcutaneous U87MG glioblastoma xenograft model (kidney 2.7 ± 0.8%ID/g; liver 1.9 ± 0.4%ID/g at 1 h p.i.). Metabolic stability of the newly synthesized tracer was also analyzed (intact tracer ranging from 75% to 99% at 1 h p.i.). In brief, the new tracer ¹⁸F-FPTA-RGD2 was synthesized with high radiochemical yield and high specific activity. This tracer exhibited good tumor-targeting efficacy and relatively good metabolic stability, as well as favorable in vivo pharmacokinetics. This new ¹⁸F labeling method based on click reaction may also be useful for radiolabeling of other biomolecules with azide groups in high yield.