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

被引：18

作者：

von Guggenberg, Elisabeth ^{[1
,2
]}

Sader, Jayden A. ^{[1
]}

Wilson, John S. ^{[1
]}

Shahhosseini, Soraya ^{[1
]}

Koslowsky, Ingrid ^{[1
]}

Wuest, Frank ^{[1
]}

Mercer, John R. ^{[1
]}

机构：

[1] Cross Canc Inst, Edmonton PET Ctr, Div Oncol Imaging, Dept Oncol, Edmonton, AB T6G 1Z2, Canada

[2] Innsbruck Med Univ, Clin Dept Nucl Med, A-6020 Innsbruck, Austria

来源：

APPLIED RADIATION AND ISOTOPES | 2009年 / 67卷 / 09期

基金：

奥地利科学基金会;

关键词：

Fluorine-18; Oligonucleotides; Alkylation; Automation; Prosthetic group; Modular synthesis unit; ANTISENSE THERAPY; N-SUCCINIMIDYL; GENERAL-METHOD; F-18; REAGENT;

D O I：

10.1016/j.apradiso.2009.04.004

中图分类号：

O61 [无机化学];

学科分类号：

070301 ; 081704 ;

摘要：

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. (C) 2009 Elsevier Ltd. All rights reserved.

引用

页码：1670 / 1675

页数：6

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