Assessment of Cu-ETS as a PET radiopharmaceutical for evaluation of regional renal perfusion

Mark A. Green, Carla J. Mathias, Lynn R. Willis, Rajash K. Handa, Jeffrey L. Lacy, Michael A. Miller, Gary D. Hutchins

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40 Scopus citations

Abstract

The copper(II) complex of ethylglyoxal bis(thiosemicarbazone) (Cu-ETS) was evaluated as a positron emission tomography (PET) radiopharmaceutical for assessment of regional renal perfusion. Methods: The concordance of renal flow estimates obtained with 11- and 15-μm microspheres was confirmed in four immature farm pigs using co-injected 46Sc- and 57Co-microspheres administered into the left ventricle. With the use of both immature farm pigs (n=3) and mature Göttingen minipigs (n=6), regional renal radiocopper uptake following intravenous [64Cu]Cu-ETS administration was compared to microsphere measurements of renal perfusion. The distribution and kinetics of [64Cu]Cu-ETS were further studied by PET imaging of the kidneys. The rate of [64Cu]Cu-ETS decomposition by blood was evaluated in vitro, employing octanol extraction to recover intact [64Cu]Cu-ETS. Results: The co-injected 11- and 15-μm microspheres provided similar estimates of renal flow. A linear relationship was observed between the renal uptake of intravenous [64Cu]Cu-ETS and regional renal perfusion measured using microspheres. [64Cu]Cu-ETS provided high-quality PET kidney images demonstrating the expected count gradient from high-flow outer cortex to low-flow medulla. When incubated with pig blood in vitro at 37°C, the [64Cu]Cu-ETS radiopharmaceutical was observed to decompose with a half-time of 2.8 min. Conclusion: Cu-ETS appears suitable for use as a PET radiopharmaceutical for evaluation of regional renal perfusion, affording renal uptake of radiocopper that varies linearly with microsphere perfusion measurements. Quantification of renal perfusion (in ml min-1 g-1) with [60,61,62,64Cu]Cu-ETS will require correcting the arterial input function for the fraction of blood radiocopper remaining present as the intact Cu-ETS radiopharmaceutical, since the Cu-ETS chelate has limited chemical stability in blood. Rapid octanol extraction of blood samples appears suitable as an approach to capturing the actual blood concentration of [60/61/62/64Cu]Cu-ETS.

Original languageEnglish (US)
Pages (from-to)247-255
Number of pages9
JournalNuclear Medicine and Biology
Volume34
Issue number3
DOIs
StatePublished - Apr 1 2007

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Keywords

  • Copper-62
  • Copper-64
  • Cu-ETS radiopharmaceutical
  • Positron emission tomography (PET)
  • Renal perfusion

ASJC Scopus subject areas

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

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