We found a match
Your institution may have access to this item. Find your institution then sign in to continue.
- Title
Elucidation of the human serum albumin (HSA) binding site for the Cu-PTSM and Cu-ATSM radiopharmaceuticals.
- Authors
Basken, Nathan E; Mathias, Carla J; Green, Mark A
- Abstract
The Cu-PTSM (pyruvaldehyde bis(N(4)-methylthiosemicarbazonato)copper(II)) and Cu-ATSM (diacetyl bis(N(4)-methylthiosemicarbazonato)copper(II)) radiopharmaceuticals exhibit strong, species-dependent binding to human serum albumin (HSA), while Cu-ETS (ethylglyoxal bis(thiosemicarbazonato)copper(II)) appears to only exhibit nonspecific binding to human and animal serum albumins. This study examines the structural basis for HSA binding of Cu-PTSM and Cu-ATSM via competition with drugs having known albumin binding sites. Warfarin, furosemide, ibuprofen, phenylbutazone, benzylpenicillin, and cephmandole were added to HSA solutions at drug:HSA mole ratios from 0 to 8:1, followed by quantification of radiopharmaceutical binding to HSA by ultrafiltration. Warfarin, a site IIA drug, progressively displaced both [(64)Cu]Cu-PTSM and [(64)Cu]Cu-ATSM from HSA. At 8:1 warfarin:HSA mole ratios, free [(64)Cu]Cu-PTSM and [(64)Cu]Cu-ATSM levels increased 300-500%. This was in contrast to solutions containing ibuprofen, a site IIIA drug; no increase in free [(64)Cu]Cu-PTSM or [(64)Cu]Cu-ATSM was observed except at high ibuprofen:HSA ratios, where secondary ibuprofen binding to the IIA site may cause modest radiopharmaceutical displacement. By contrast, and consistent with earlier findings suggesting Cu-ETS exhibits only nonspecific associations, [(64)Cu]Cu-ETS binding to HSA was unaffected by the addition of drugs that bind in either site. We conclude that the species-dependence of Cu-PTSM and Cu-ATSM albumin binding arises from interaction(s) with the IIA site of HSA.
- Publication
Journal of pharmaceutical sciences, 2009, Vol 98, Issue 6, p2170
- ISSN
1520-6017
- Publication type
Journal Article
- DOI
10.1002/jps.21570