title: Species dependence of [64Cu]Cu-Bis(thiosemicarbazone) radiopharmaceutical binding to serum albumins.
abstract: BACKGROUND
  Interactions of three copper(II) bis(thiosemicarbazone) positron emission tomography radiopharmaceuticals with human serum albumin, and the serum albumins of four additional mammalian species, were evaluated.
  
  
  METHODS
  64Cu-labeled diacetyl bis(N4-methylthiosemicarbazonato)copper(II) (Cu-ATSM), pyruvaldehyde bis(N4-methylthiosemicarbazonato)copper(II) (Cu-PTSM) and ethylglyoxal bis(thiosemicarbazonato)copper(II) (Cu-ETS) were synthesized and their binding to human, canine, rat, baboon and porcine serum albumins quantified by ultrafiltration. Protein binding was also measured for each tracer in human, porcine, rat and mouse serum.
  
  
  RESULTS
  The interaction of these neutral, lipophilic copper chelates with serum albumin is highly compound- and species-dependent. Cu-PTSM and Cu-ATSM exhibit particularly high affinity for human serum albumin (HSA), while the albumin binding of Cu-ETS is relatively insensitive to species. At HSA concentrations of 40 mg/ml, "% free" (non-albumin-bound) levels of radiopharmaceutical were 4.0+/-0.1%, 5.3+/-0.2% and 38.6+/-0.8% for Cu-PTSM, Cu-ATSM and Cu-ETS, respectively.
  
  
  CONCLUSIONS
  Species-dependent variations in radiopharmaceutical binding to serum albumin may need to be considered when using animal models to predict the distribution and kinetics of these compounds in humans.
authors: Division of Nuclear Pharmacy, Department of Industrial and Physical Pharmacy, Purdue University, West Lafayette, IN 47907, USA. nbasken@purdue.edu
authors: Nathan E
authors: NE
authors: Basken
authors: Carla J
authors: CJ
authors: Mathias
authors: Alexander E
authors: AE
authors: Lipka
authors: Mark A
authors: MA
authors: Green
mesh_terms: D000818:Animals; D002846:Chromatography, Affinity; D056831:Coordination Complexes; D003301:Copper Radioisotopes / Q000737:chemistry; D004285:Dogs; D006801:Humans; D051379:Mice; D009942:Organometallic Compounds / Q000138:chemical synthesis / Q000737:chemistry / Q000493:pharmacokinetics*; D010215:Papio; D049268:Positron-Emission Tomography; D011485:Protein Binding; D019275:Radiopharmaceuticals / Q000138:chemical synthesis / Q000737:chemistry; D051381:Rats; D012709:Serum Albumin / Q000737:chemistry*; D013045:Species Specificity; D013329:Structure-Activity Relationship; D013552:Swine; D013882:Thiosemicarbazones / Q000138:chemical synthesis / Q000737:chemistry* / Q000493:pharmacokinetics; D014462:Ultrafiltration
chemical_list: D056831:Coordination Complexes; D003301:Copper Radioisotopes; D009942:Organometallic Compounds; D019275:Radiopharmaceuticals; D012709:Serum Albumin; D013882:Thiosemicarbazones; C089548:copper (II) diacetyl-di(N(4)-methylthiosemicarbazone); C530436:ethylglyoxal bis(thiosemicarbazonato)copper(II); C052629:copper pyruvaldehyde bis(N(4)-methylthiosemicarbazone) complex