title: Very stable 188Re-S4 chelates for labelling biomolecules: preparation with highly concentrated perrhenate eluates.
abstract: OBJECTIVE
  The preparation and stability of a new (188)Re-S(4)-complex [S(4) = (1-aza-18-crown-6)(O)C-C(SH)-C(SH)-C(O)NH-(CH(2))(3)-NH-(CH(2))(3)-NHC(O)-C(SH)-C(SH)-C(O)(1-aza-18-crown-6] was studied at therapeutic relevant radioactive concentrations. The results were compared with (188)Re-MAG(3) (MAG(3): mercaptoacetyltriglycine) and (188)Re-DMSA preparations (DMSA: dimercaptosuccinic acid) performed with the same highly concentrated [(188)Re]perrhenate solution (12-15 GBq/ml).
  
  
  METHODS
  The (188)Re complexes were prepared by direct reduction of perrhenate ((188)Re-S(4)-complex) as well as via the (188)Re-EDTA precursor complex ((188)Re-MAG(3), (188)Re-DMSA). The preparations were stabilised with 15 mg of ascorbic acid and analysed after 1, 2, and 24 hours by TLC and HPLC. Additionally, in vitro and in vivo stability studies were performed with the purified complexes.
  
  
  RESULTS
  After stabilisation with 15 mg of ascorbic acid, all of the complexes were nearly stable under nitrogen for hours, and only 2-8% of perrhenate was observed after 24 h. In contrast, only the (188)Re-S(4) complex was completely stable in vitro and in all investigated in vivo samples after separation of ligand excess and reducing agent by HPLC.
  
  
  CONCLUSIONS
  The bridging amine group or free carboxylic groups of the S(4)-ligand framework make available reactive positions for coupling biomolecules to the chelate. Thus it appears that the new (188)Re-S(4) complexes offer the possibility of stable and high specific activity labelling of biomolecules for therapeutic application.
authors.affiliation: Institut für Radiopharmazie, Forschungszentrum Dresden-Rossendorf, PF 510119, 01314 Dresden, Germany. s.seifert@fzd.de
authors.forename: S
authors.initials: S
authors.lastname: Seifert
authors.forename: C
authors.initials: C
authors.lastname: Jentschel
authors.forename: R
authors.initials: R
authors.lastname: Bergmann
authors.forename: H-J
authors.initials: HJ
authors.lastname: Pietzsch
authors.forename: G
authors.initials: G
authors.lastname: Wunderlich
authors.forename: J
authors.initials: J
authors.lastname: Kotzerke
authors.forename: J
authors.initials: J
authors.lastname: Steinbach
mesh_terms: D004355:Drug Stability; D007553:Isotope Labeling / Q000379:methods*; D008024:Ligands; D008958:Models, Molecular; D011868:Radioisotopes; D012211:Rhenium / Q000032:analysis
chemical_list: D008024:Ligands; D011868:Radioisotopes; C015428:perrhenate; D012211:Rhenium