title: Neurotensin(8-13) analogue: radiolabeling and biological evaluation using different chelators.
abstract: BACKGROUND
  Several strategies on the development of radiopharmaceuticals have been employed. Bifunctional chelators seem to be a promising approach since high radiochemical yields as well as good in vitro and in vivo stability have been achieved. To date, neurotensin analogs have been radiolabeled using the (99m)Tc-carbonyl approach and none was described employing the bifunctional chelating agent technique.
  
  
  OBJECTIVE
  The purpose of this study was to evaluate the radiochemical and biological behaviour of NT(8-13) analogue radiolabeled with (99m)Tc, using HYNIC and NHS-S-acetyl-MAG(3) as chelator agents.
  
  
  METHODS
  Radiolabeling, in vitro stability toward cysteine and glutathione, partition coefficient and plasma protein binding were assessed for both radioconjugates. Biodistribution in healthy Swiss mice were carried out in order to evaluate the biological behaviour of the radiocomplexes.
  
  
  RESULTS
  Radiochemical yields were higher than 97% and no apparent instability toward transchelant agents was observed for both radioconjugates. A higher lipophilic character was observed for the radioconjugate labeled via MAG(3). The chelators seem to have no effect on the percentage of the radioconjugate bound to plasma proteins. A similar biological pattern was observed for both radioconjugates. Total blood, bone and muscle values revealed a slightly slower clearance for the radiocomplex labeled via MAG(3). Moreover, a remarkable liver and intestinal uptake was observed for the radiocomplex labeled via MAG(3) even at the later time points studied.
  
  
  CONCLUSIONS
  The high radiochemical yields achieved and the similar in vivo pattern found for both radioconjugates make them potential candidates for imaging tumors using nuclear medicine techniques.
authors.affiliation: Center of Radiopharmacy, Institute of Energetic and Nuclear Research, Sao Paulo, SP 05508-000, Brazil. teodoro_rodrigo@yahoo.com.br
authors.forename: Rodrigo
authors.initials: R
authors.lastname: Teodoro
authors.forename: Bluma Linkowski
authors.initials: BL
authors.lastname: Faintuch
authors.forename: Eutimio Gustavo Fernández
authors.initials: EG
authors.lastname: Núñez
authors.forename: Rodrigo Guimarães
authors.initials: RG
authors.lastname: Queiróz
mesh_terms: D000818:Animals; D001798:Blood Proteins / Q000378:metabolism; D002614:Chelating Agents / Q000737:chemistry*; D003432:Cross-Linking Reagents / Q000737:chemistry*; D003545:Cysteine / Q000737:chemistry; D004355:Drug Stability; D005260:Female; D005978:Glutathione / Q000737:chemistry; D006834:Hydrazines / Q000737:chemistry*; D007553:Isotope Labeling / Q000379:methods*; D051379:Mice; D009496:Neurotensin / Q000097:blood / Q000737:chemistry* / Q000378:metabolism / Q000493:pharmacokinetics; D009539:Nicotinic Acids / Q000737:chemistry*; D009842:Oligopeptides / Q000737:chemistry*; D015609:Organotechnetium Compounds / Q000737:chemistry*; D010446:Peptide Fragments / Q000097:blood / Q000737:chemistry* / Q000378:metabolism / Q000493:pharmacokinetics; D011854:Radiochemistry; D013388:Succinimides / Q000737:chemistry*
chemical_list: C120392:6-hydrazinopyridine-3-carboxylic acid; D001798:Blood Proteins; D002614:Chelating Agents; D003432:Cross-Linking Reagents; D006834:Hydrazines; D009539:Nicotinic Acids; D009842:Oligopeptides; D015609:Organotechnetium Compounds; D010446:Peptide Fragments; C118517:S-acetylmercaptoacetyltriglycine N-hydroxysuccinimide; D013388:Succinimides; D009496:Neurotensin; C054381:neurotensin (8-13); D005978:Glutathione; D003545:Cysteine