title: Automated synthesis of an 18F-labelled pyridine-based alkylating agent for high yield oligonucleotide conjugation.
abstract: 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-[(18)F]fluoropyridin-3-yloxy)propyl]acetamide ([(18)F]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/micromoL. 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.
authors.affiliation: Edmonton PET Centre, Division of Oncologic Imaging, Department of Oncology, Cross Cancer Institute, Edmonton, AB, Canada.
authors.forename: Elisabeth
authors.initials: E
authors.lastname: von Guggenberg
authors.forename: Jayden A
authors.initials: JA
authors.lastname: Sader
authors.forename: John S
authors.initials: JS
authors.lastname: Wilson
authors.forename: Soraya
authors.initials: S
authors.lastname: Shahhosseini
authors.forename: Ingrid
authors.initials: I
authors.lastname: Koslowsky
authors.forename: Frank
authors.initials: F
authors.lastname: Wuest
authors.forename: John R
authors.initials: JR
authors.lastname: Mercer
mesh_terms: D000081:Acetamides / Q000138:chemical synthesis* / Q000737:chemistry; D000477:Alkylating Agents / Q000138:chemical synthesis* / Q000737:chemistry; D005462:Fluorine Radioisotopes; D009841:Oligonucleotides / Q000737:chemistry*; D011725:Pyridines / Q000138:chemical synthesis* / Q000737:chemistry; D019275:Radiopharmaceuticals / Q000138:chemical synthesis* / Q000737:chemistry
chemical_list: C493997:2-bromo-N-(3-(2-fluoropyridin-3-yloxy)propyl)acetamide; D000081:Acetamides; D000477:Alkylating Agents; D005462:Fluorine Radioisotopes; D009841:Oligonucleotides; D011725:Pyridines; D019275:Radiopharmaceuticals