title: ¹⁸F-labeled silicon-based fluoride acceptors: potential opportunities for novel positron emitting radiopharmaceuticals.
abstract: BACKGROUND
  Over the recent years, radiopharmaceutical chemistry has experienced a wide variety of innovative pushes towards finding both novel and unconventional radiochemical methods to introduce fluorine-18 into radiotracers for positron emission tomography (PET). These "nonclassical" labeling methodologies based on silicon-, boron-, and aluminium-(18)F chemistry deviate from commonplace bonding of an [(18)F]fluorine atom ((18)F) to either an aliphatic or aromatic carbon atom. One method in particular, the silicon-fluoride-acceptor isotopic exchange (SiFA-IE) approach, invalidates a dogma in radiochemistry that has been widely accepted for many years: the inability to obtain radiopharmaceuticals of high specific activity (SA) via simple IE.
  
  
  METHODS
  The most advantageous feature of IE labeling in general is that labeling precursor and labeled radiotracer are chemically identical, eliminating the need to separate the radiotracer from its precursor. SiFA-IE chemistry proceeds in dipolar aprotic solvents at room temperature and below, entirely avoiding the formation of radioactive side products during the IE.
  
  
  METHODS
  A great plethora of different SiFA species have been reported in the literature ranging from small prosthetic groups and other compounds of low molecular weight to labeled peptides and most recently affibody molecules.
  
  
  CONCLUSIONS
  The literature over the last years (from 2006 to 2014) shows unambiguously that SiFA-IE and other silicon-based fluoride acceptor strategies relying on (18)F(-) leaving group substitutions have the potential to become a valuable addition to radiochemistry.
authors.affiliation: Division of Experimental Medicine, Department of Medicine, McGill University, 1110 Pine Avenue West, Montreal, QC, Canada H3A 1A3.
authors.forename: Vadim
authors.initials: V
authors.lastname: Bernard-Gauthier
authors.affiliation: Biomedical Chemistry, Department of Clinical Radiology and Nuclear Medicine, Medical Faculty Mannheim of Heidelberg University, 68167 Mannheim, Germany.
authors.forename: Carmen
authors.initials: C
authors.lastname: Wängler
authors.affiliation: McConnell Brain Imaging Centre, Montreal Neurological Institute, McGill University, 3801 University Street, Montreal, QC, Canada H3A 2B4.
authors.forename: Esther
authors.identifier: 0000-0003-4988-7821
authors.initials: E
authors.lastname: Schirrmacher
authors.affiliation: McConnell Brain Imaging Centre, Montreal Neurological Institute, McGill University, 3801 University Street, Montreal, QC, Canada H3A 2B4.
authors.forename: Alexey
authors.identifier: 0000-0003-1646-761X
authors.initials: A
authors.lastname: Kostikov
authors.affiliation: Department of Inorganic Chemistry II, Faculty of Chemistry, TU Dortmund, Otto-Hahn-Straße 6, 44221 Dortmund, Germany.
authors.forename: Klaus
authors.identifier: 0000-0001-9930-858X
authors.initials: K
authors.lastname: Jurkschat
authors.affiliation: Molecular Imaging and Radiochemistry, Department of Clinical Radiology and Nuclear Medicine, Medical Faculty Mannheim of Heidelberg University, 68167 Mannheim, Germany.
authors.forename: Bjoern
authors.initials: B
authors.lastname: Wängler
authors.affiliation: McConnell Brain Imaging Centre, Montreal Neurological Institute, McGill University, 3801 University Street, Montreal, QC, Canada H3A 2B4 ; Department of Oncology, University of Alberta, 11560 University Avenue, Edmonton, AB, Canada T6G 1Z2.
authors.forename: Ralf
authors.initials: R
authors.lastname: Schirrmacher
mesh_terms: D005459:Fluorides / Q000737:chemistry; D005462:Fluorine Radioisotopes / Q000737:chemistry; D006868:Hydrolysis; D010455:Peptides / Q000737:chemistry; D049268:Positron-Emission Tomography; D019275:Radiopharmaceuticals / Q000737:chemistry; D017655:Silicon Compounds / Q000737:chemistry
chemical_list: D005462:Fluorine Radioisotopes; D010455:Peptides; D019275:Radiopharmaceuticals; D017655:Silicon Compounds; C054375:silicon fluoride; D005459:Fluorides