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

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

doi:10.1016/j.nucmedbio.2007.01.002

« Previous Next »Nuclear Medicine and Biology
Volume 34, Issue 3 , Pages 247-255, April 2007

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

Mark A. Green
- Department of Industrial and Physical Pharmacy, Purdue University, West Lafayette, IN 47907, USA
- Corresponding author. Purdue University, West Lafayette, IN 47907-2091, USA. Tel.: +1 765 494 1445; fax: +1 765 496 3367.
Carla J. Mathias
- Department of Industrial and Physical Pharmacy, Purdue University, West Lafayette, IN 47907, USA
Lynn R. Willis
- Department of Pharmacology and Toxicology, Indiana University School of Medicine, Indianapolis, IN 46202, USA
Rajash K. Handa
- Department of Pharmacology and Toxicology, Indiana University School of Medicine, Indianapolis, IN 46202, USA
Jeffrey L. Lacy
- Proportional Technologies, Inc., Houston, TX 77054, USA
Michael A. Miller
- Department of Radiology and the Indiana Center of Excellence in Biomedical Imaging, Indiana University School of Medicine, Indianapolis, IN 46202, USA
Gary D. Hutchins
- Department of Radiology and the Indiana Center of Excellence in Biomedical Imaging, Indiana University School of Medicine, Indianapolis, IN 46202, USA

Received 23 October 2006; received in revised form 19 December 2006; accepted 2 January 2007.

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.

Keywords: Renal perfusion, Copper-62, Copper-64, Cu-ETS radiopharmaceutical, Positron emission tomography (PET)