title: Iodine-129 microdosing for protein and peptide drug development: erythropoietin as a case study.
abstract: BACKGROUND
  Microdosing is a technique for studying the behavior of compounds in vivo at 1/100th of the dose of a test substance calculated, based on animal data, to yield a pharmacologic effect. In microdosing, use is made of accelerator MS (AMS). In this study, we investigated whether (129)I-labeling of proteins with subsequent AMS measurements is a suitable method to perform microdose studies with therapeutic proteins. We used erythropoietin (EPO) as a case study.
  
  
  RESULTS
  In an animal study with (129)I-labeled EPO in Han-Wistar rats, an increase of (129)I-EPO is observed after dose administration. The half-life was found to be 2 and 5.5 h for two different EPOs. These results are in accordance with expected values.
  
  
  CONCLUSIONS
  Although further research is required, (129)I-labeling of proteins seems a feasible method for AMS microdose studies with peptide and protein drugs, such as biosimilars.
authors.affiliation: r.lamers@abundnz.com
authors.forename: Robert-Jan An
authors.initials: RJ
authors.lastname: Lamers
authors.forename: Arie Fm
authors.initials: AF
authors.lastname: de Jong
authors.forename: José M
authors.initials: JM
authors.lastname: López-Gutiérrez
authors.forename: Jm
authors.initials: J
authors.lastname: Gómez-Guzmán
mesh_terms: D000054:Acceleration; D000818:Animals; D002853:Chromatography, Liquid; D004305:Dose-Response Relationship, Drug; D055808:Drug Discovery / Q000379:methods*; D004921:Erythropoietin / Q000008:administration & dosage / Q000097:blood* / Q000737:chemistry / Q000493:pharmacokinetics; D005240:Feasibility Studies; D006207:Half-Life; D006801:Humans; D007456:Iodine Isotopes / Q000097:blood / Q000737:chemistry; D008297:Male; D013058:Mass Spectrometry; D051381:Rats; D017208:Rats, Wistar; D020349:Surface Plasmon Resonance
chemical_list: D007456:Iodine Isotopes; D004921:Erythropoietin