title: Characterization of iodinated adrenomedullin derivatives suitable for lung nuclear medicine.
abstract: BACKGROUND
  We have recently demonstrated the effectiveness of 99m-technetium adrenomedullin (AM) as a new molecular lung imaging agent that could provide significant advantages for the diagnosis and follow-up of disorders affecting the pulmonary circulation such as pulmonary embolism and pulmonary hypertension. Having the possibility to conjugate the targeting molecule with different radionuclides would offer more flexibility and potential advantages depending on clinical situations. Since various iodine isotopes are currently used in nuclear medicine and in pharmacological studies, we have evaluated which iodination method should be privileged in order to produce a good iodinated AM-derived nuclear medicine agent.
  
  
  METHODS
  Synthetic AM was labeled with iodine through chemical and lactoperoxidase oxidation methods. Position of the iodine atom on the peptide was determined by MALDI-TOF mass spectrometry analysis following cyanogen bromide cleavage and carboxypeptidase Y digestion. Binding affinity of iodinated AM analogues was evaluated by competition and saturation binding experiments on dog lung preparations.
  
  
  RESULTS
  In this study, we demonstrated that, upon lactoperoxidase oxidation, iodination occurred at Tyr(1) and that this radioligand retained higher binding affinity and specificity over preparations obtained through chemical oxidation.
  
  
  CONCLUSIONS
  These results emphasize the fact that even a small chemical modification, i.e. iodination, might deeply modify the pharmacological profile of a compound and support observations that the C-terminal tail of human AM plays an important role in the AM receptor binding process. Consequently, incorporation of a radionuclide to produce an AM-based nuclear medicine agent should privilege the N-terminus of the molecule.
authors.affiliation: Laboratoire d'Études Moléculaires et Pharmacologiques des Peptides, INRS-Institut Armand-Frappier, Ville de Laval, Qc, Canada.
authors.forename: Yan
authors.initials: Y
authors.lastname: Fu
authors.forename: Myriam
authors.initials: M
authors.lastname: Létourneau
authors.forename: David
authors.initials: D
authors.lastname: Chatenet
authors.forename: Jocelyn
authors.initials: J
authors.lastname: Dupuis
authors.forename: Alain
authors.initials: A
authors.lastname: Fournier
mesh_terms: D053607:Adrenomedullin / Q000737:chemistry* / Q000378:metabolism*; D000818:Animals; D001665:Binding Sites; D004285:Dogs; D006801:Humans; D007455:Iodine / Q000737:chemistry*; D007784:Lactoperoxidase / Q000378:metabolism; D008168:Lung / Q000378:metabolism*; D009683:Nuclear Medicine / Q000379:methods*; D015609:Organotechnetium Compounds / Q000737:chemistry / Q000378:metabolism; D010084:Oxidation-Reduction; D013379:Substrate Specificity
chemical_list: D015609:Organotechnetium Compounds; D053607:Adrenomedullin; D007455:Iodine; D007784:Lactoperoxidase