title: Synthesis, characterization and biodistribution studies of (125)I-radioiodinated di-PEGylated bone targeting salmon calcitonin analogue in healthy rats.
abstract: OBJECTIVE
  The objective of this study was to prepare a bisphosphonate (BP) mediated bone targeting di-PEGylated salmon calcitonin analogue sCT-2(PEG-BP) as a novel bone targeting pharmaceutical.
  
  
  METHODS
  HPLC was used for isolation of sCT-2(PEG-BP) from the reaction mixture, followed by determination of possible PEGylation sites by trypsin digestion. Stability of the compound over time, bone mineral affinity using hydroxyapatite, and biodistribution in normal rats after radiolabeling of sCT-2(PEG-BP) or control sCT with (125)I was evaluated.
  
  
  RESULTS
  PEGylated sCT analogues were synthesized, and sCT-2(PEG-BP) was isolated by HPLC and confirmed by MALDI-TOF and ICP-MS. MALDI-TOF analysis of trypsinized fragments suggested Cys(1) (or Lys(11)) and Lys(18) to be the two PEGylation sites. Bone mineral affinity test showed sCT-2(PEG-BP) or (125)I-sCT-2(PEG-BP) exhibited significantly increased bone mineral affinity over sCT or (125)I-sCT, respectively. sCT-2(PEG-BP) remained stable for at least 1 month. In vivo biodistribution study showed significantly increased bone retention and prolonged plasma circulation time for sCT-2(PEG-BP) compared to the control sCT.
  
  
  CONCLUSIONS
  Those results support sCT-2(PEG-BP) as a promising new drug candidate for the treatment of resorptive and/or maladaptive bone conditions, such as Osteoporosis, Osteoarthritis, Rheumatoid Arthritis, Paget's disease and bone cancers.
authors.affiliation: Pharmaceutical Orthopaedic Research Laboratory Faculty of Pharmacy & Pharmaceutical Sciences, University of Alberta, Edmonton, Alberta, T6G 2E1, Canada.
authors.forename: Yang
authors.initials: Y
authors.lastname: Yang
authors.forename: Krishna H
authors.initials: KH
authors.lastname: Bhandari
authors.forename: Arash
authors.initials: A
authors.lastname: Panahifar
authors.forename: Michael R
authors.initials: MR
authors.lastname: Doschak
mesh_terms: D000818:Animals; D002116:Calcitonin / Q000378:metabolism*; D002851:Chromatography, High Pressure Liquid; D005260:Female; D007457:Iodine Radioisotopes / Q000493:pharmacokinetics*; D011092:Polyethylene Glycols / Q000378:metabolism*; D051381:Rats; D017207:Rats, Sprague-Dawley; D019032:Spectrometry, Mass, Matrix-Assisted Laser Desorption-Ionization; D014018:Tissue Distribution
chemical_list: D007457:Iodine Radioisotopes; D011092:Polyethylene Glycols; C028815:salmon calcitonin; D002116:Calcitonin