Species-dependent binding of copper(II) bis(thiosemicarbazone) radiopharmaceuticals to serum albumin

C. J. Mathias, S. R. Bergmann, Mark Green

Research output: Contribution to journalArticle

35 Citations (Scopus)

Abstract

Copper-62-labeled pyruvaldehyde bis(N4-methylthiosemicarbazonato)- copper(II) (Cu-PTSM) is a generator-based PET radio-pharmaceutical under investigation for use in evaluation of tissue perfusion. Despite promising results from animals, problems have been encountered in the use of 62Cu- PTSM to quantitate myocardial perfusion in humans at high flow rates, possibly due to species-dependent interactions of the tracer with serum albumin. Methods: Ultrafiltration and plasma/erythrocyte partitioning studies were performed to assess the protein binding of 67Cu-labeled Cu-PTSM and six related copper(II) bis(thiosemicarbazone) complexes. Results: These studies reveal significant interspecies variability in the strength of Cu- PTSM binding to serum albumin, with 67Cu-PTSM binding much more strongly to human albumin than to dog albumin. Most of the related Cu(II)- bis(thiosemicarbazone) complexes examined exhibit interspecies variability of albumin binding similar to that observed with Cu-PTSM. Two such complexes, Cu-ETS and Cu-n-PrTS, however, were identified that exhibit no preferential association with human serum albumin. Conclusion: Copper-62-PTSM exhibits substantial interspecies variability in the strength of its binding to serum albumin, which appears to explain the problems encountered in using animal data to predict 62Cu-PTSM behavior in humans. The 62Cu-ETS and 62Cu-n- PrTS complexes may be viable alternatives to 62Cu-PTSM for PET studies to evaluate quantitatively myocardial blood flow in humans.

Original languageEnglish (US)
Pages (from-to)1451-1455
Number of pages5
JournalJournal of Nuclear Medicine
Volume36
Issue number8
StatePublished - 1995
Externally publishedYes

Fingerprint

Thiosemicarbazones
Radiopharmaceuticals
Serum Albumin
Copper
Albumins
Perfusion
Pyruvaldehyde
Ultrafiltration
Radio
Protein Binding
Erythrocytes
Dogs
copper pyruvaldehyde bis(N(4)-methylthiosemicarbazone) complex
Pharmaceutical Preparations

Keywords

  • albumin binding
  • copper(II) bis(thiosemicarbazone)
  • positron emission tomography
  • ultrafiltration

ASJC Scopus subject areas

  • Radiological and Ultrasound Technology

Cite this

Species-dependent binding of copper(II) bis(thiosemicarbazone) radiopharmaceuticals to serum albumin. / Mathias, C. J.; Bergmann, S. R.; Green, Mark.

In: Journal of Nuclear Medicine, Vol. 36, No. 8, 1995, p. 1451-1455.

Research output: Contribution to journalArticle

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abstract = "Copper-62-labeled pyruvaldehyde bis(N4-methylthiosemicarbazonato)- copper(II) (Cu-PTSM) is a generator-based PET radio-pharmaceutical under investigation for use in evaluation of tissue perfusion. Despite promising results from animals, problems have been encountered in the use of 62Cu- PTSM to quantitate myocardial perfusion in humans at high flow rates, possibly due to species-dependent interactions of the tracer with serum albumin. Methods: Ultrafiltration and plasma/erythrocyte partitioning studies were performed to assess the protein binding of 67Cu-labeled Cu-PTSM and six related copper(II) bis(thiosemicarbazone) complexes. Results: These studies reveal significant interspecies variability in the strength of Cu- PTSM binding to serum albumin, with 67Cu-PTSM binding much more strongly to human albumin than to dog albumin. Most of the related Cu(II)- bis(thiosemicarbazone) complexes examined exhibit interspecies variability of albumin binding similar to that observed with Cu-PTSM. Two such complexes, Cu-ETS and Cu-n-PrTS, however, were identified that exhibit no preferential association with human serum albumin. Conclusion: Copper-62-PTSM exhibits substantial interspecies variability in the strength of its binding to serum albumin, which appears to explain the problems encountered in using animal data to predict 62Cu-PTSM behavior in humans. The 62Cu-ETS and 62Cu-n- PrTS complexes may be viable alternatives to 62Cu-PTSM for PET studies to evaluate quantitatively myocardial blood flow in humans.",
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N2 - Copper-62-labeled pyruvaldehyde bis(N4-methylthiosemicarbazonato)- copper(II) (Cu-PTSM) is a generator-based PET radio-pharmaceutical under investigation for use in evaluation of tissue perfusion. Despite promising results from animals, problems have been encountered in the use of 62Cu- PTSM to quantitate myocardial perfusion in humans at high flow rates, possibly due to species-dependent interactions of the tracer with serum albumin. Methods: Ultrafiltration and plasma/erythrocyte partitioning studies were performed to assess the protein binding of 67Cu-labeled Cu-PTSM and six related copper(II) bis(thiosemicarbazone) complexes. Results: These studies reveal significant interspecies variability in the strength of Cu- PTSM binding to serum albumin, with 67Cu-PTSM binding much more strongly to human albumin than to dog albumin. Most of the related Cu(II)- bis(thiosemicarbazone) complexes examined exhibit interspecies variability of albumin binding similar to that observed with Cu-PTSM. Two such complexes, Cu-ETS and Cu-n-PrTS, however, were identified that exhibit no preferential association with human serum albumin. Conclusion: Copper-62-PTSM exhibits substantial interspecies variability in the strength of its binding to serum albumin, which appears to explain the problems encountered in using animal data to predict 62Cu-PTSM behavior in humans. The 62Cu-ETS and 62Cu-n- PrTS complexes may be viable alternatives to 62Cu-PTSM for PET studies to evaluate quantitatively myocardial blood flow in humans.

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