title: Synthesis and structural identification of fluorine-18 labeled parathyroid hormone.
abstract: Parathyroid hormone (PTH) is an 84 amino acid peptide hormone that plays a key role in bone and mineral metabolism. The biological actions of PTH are mediated via the N-terminal PTH(1-34) fragment, serving as the PTH receptor-binding sequence, and which is therefore used clinically to treat conditions of low bone mass such as osteoporosis. In this study, PTH(1-34) was conjugated with non-radioactive (stable F isotope) N-succinimidyl 4-fluorobenzoate (SFB) leading to three isomeric mono-fluorobenzoated (FBz) PTH followed by Liquid chromatography-Tandem mass spectrometry (LC-MS/MS) assisted structural identification. Corresponding [(18)F]SFB-labeled PTH derivatives were prepared respectively and the Lys(13) site-specific labeled [(18)F]FBz PTH was isolated by HPLC with radiochemical purity >99% and specific activity of 2.78 GBq/µmol, suitable for future application with in vivo pharmacokinetic/pharmacodynamic studies of PTH, using preclinical Positron Emission Tomography Computed Tomography (PET/CT) imaging.
authors.affiliation: Pharmaceutical Orthopaedic Research Lab, Faculty of Pharmacy and Pharmaceutical Sciences, University of Alberta, Edmonton, Alberta, Canada.
authors.forename: Yang
authors.initials: Y
authors.lastname: Yang
authors.affiliation: Department of Oncology, University of Alberta, Edmonton, Alberta, Canada.
authors.forename: Susan
authors.initials: S
authors.lastname: Richter
authors.affiliation: Department of Oncology, University of Alberta, Edmonton, Alberta, Canada.
authors.forename: Frank
authors.initials: F
authors.lastname: Wuest
authors.affiliation: Pharmaceutical Orthopaedic Research Lab, Faculty of Pharmacy and Pharmaceutical Sciences, University of Alberta, Edmonton, Alberta, Canada.
authors.forename: Michael R
authors.initials: MR
authors.lastname: Doschak
mesh_terms: D000595:Amino Acid Sequence; D005462:Fluorine Radioisotopes / Q000737:chemistry*; D008969:Molecular Sequence Data; D010281:Parathyroid Hormone / Q000138:chemical synthesis* / Q000737:chemistry; D019275:Radiopharmaceuticals / Q000138:chemical synthesis* / Q000737:chemistry
chemical_list: D005462:Fluorine Radioisotopes; D010281:Parathyroid Hormone; D019275:Radiopharmaceuticals
keywords: 18F-radiolabeling; HPLC; LC-MS/MS; N-Succinimidyl-4-fluorobenzoate (SFB); Structural identification; parathyroid hormone