Species dependence of [64Cu]Cu-Bis(thiosemicarbazone) radiopharmaceutical binding to serum albumins

Nathan E. Basken, Carla J. Mathias, Alexander E. Lipka, Mark A. Green

Research output: Contribution to journalArticlepeer-review


Introduction: 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.

Original languageEnglish (US)
Pages (from-to)281-286
Number of pages6
JournalNuclear Medicine and Biology
Issue number3
StatePublished - Apr 2008
Externally publishedYes


  • Copper-64
  • Cu-ATSM
  • Cu-ETS
  • Cu-PTSM
  • Serum albumin binding

ASJC Scopus subject areas

  • Molecular Medicine
  • Radiology Nuclear Medicine and imaging
  • Cancer Research


Dive into the research topics of 'Species dependence of [<sup>64</sup>Cu]Cu-Bis(thiosemicarbazone) radiopharmaceutical binding to serum albumins'. Together they form a unique fingerprint.

Cite this