One-step (18)F labeling of biomolecules using organotrifluoroborates

Nat Protoc. 2015 Sep;10(9):1423-32. doi: 10.1038/nprot.2015.090. Epub 2015 Aug 27.

Abstract

Herein we present a general protocol for the functionalization of biomolecules with an organotrifluoroborate moiety so that they can be radiolabeled with aqueous (18)F fluoride ((18)F(-)) and used for positron emission tomography (PET) imaging. Among the β(+)-emitting radionuclides, fluorine-18 ((18)F) is the isotope of choice for PET, and it is produced, on-demand, in many hospitals worldwide. Organotrifluoroborates can be (18)F-labeled in one step in aqueous conditions via (18)F-(19)F isotope exchange. This protocol features a recently designed ammoniomethyltrifluoroborate, and it describes the following: (i) a synthetic strategy that affords modular synthesis of radiolabeling precursors via a copper-catalyzed 'click' reaction; and (ii) a one-step (18)F-labeling method that obviates the need for HPLC purification. Within 30 min, (18)F-labeled PET imaging probes, such as peptides, can be synthesized in good chemical and radiochemical purity (>98%), satisfactory radiochemical yield of 20-35% (n > 20, non-decay corrected) and high specific activity of 40-111 GBq/μmol (1.1-3.0 Ci/μmol). The entire procedure, including the precursor preparation and (18)F radiolabeling, takes 7-10 d.

Publication types

  • Research Support, N.I.H., Intramural
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Boron Compounds / chemistry*
  • Fluorine Radioisotopes / chemistry*
  • Isotope Labeling / methods*
  • Octreotide / analogs & derivatives*
  • Octreotide / chemistry

Substances

  • AMBF3-TATE
  • Boron Compounds
  • Fluorine Radioisotopes
  • Octreotide