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

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-mu m microspheres was confirmed in four immature farm pigs using co-injected Sc-46- and Co-57-microspheres administered into the left ventricle. With the use of both immature farm pigs (n=3) and mature Gottingen minipigs (n = 6), regional renal radiocopper uptake following intravenous [Cu-64] Cu-ETS administration was compared to microsphere measurements of renal perfusion. The distribution and kinetics of [Cu-64] Cu-ETS were further studied by PET imaging of the kidneys. The rate of [Cu-64]Cu-ETS decomposition by blood was evaluated in vitro, employing octanol extraction to recover intact [Cu-64]Cu-ETS. Results: The co-injected 11- and 15-mu m microspheres provided similar estimates of renal flow. A linear relationship was observed between the renal uptake of intravenous [(64) Cu]Cu-ETS and regional renal perfusion measured using microspheres. [Cu-64]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 pie blood in vitro at 37 degrees C, the [Cu-64] 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 [Cu-60,Cu-61.62.64]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 [Cu-60/61/62/64] Cu-ETS. (c) 2007 Elsevier Inc. All rights reserved.