Automated synthesis of an F-18-labelled pyridine-based alkylating agent for high yield oligonucleotide conjugation

作者：von Guggenberg Elisabeth; Sader Jayden A; Wilson John S; Shahhosseini Soraya; Koslowsky Ingrid; Wuest Frank; Mercer John R^*

来源：Applied Radiation and Isotopes, 2009, 67(9): 1670-1675.

DOI：10.1016/j.apradiso.2009.04.004

• Fluorine-18
• Oligonucleotides
• Alkylation
• Automation
• Prosthetic group
• Modular synthesis unit

Alkylating agents have been shown to be very promising for the radiolabelling of oligonucleotides with fluorine-18. In this report we describe the fully automated synthesis of 2-bromo-N-[3-(2-[F-18]fluoropyridin-3-yloxy)propyl]acetamide ([F-18]FPyBrA) utilizing a modular synthesis unit. Reaction conditions for the coupling of this pyridine-based alkylating agent at the 5' end of a fully phosphorothioated random 20-mer DNA sequence were optimized to achieve very high radiochemical yields (> 90%) and a maximum specific activity of 5-6 GBq/mu moL The potential for rapid purification by solid phase extraction without need of chromatographic isolation of the radiolabelled oligonucleotide presents an overall benefit for the application of oligonucleotides in preclinical studies and potential clinical applications.

• 出版日期2009-9