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-microm microspheres was confirmed in four immature farm pigs using co-injected (46)Sc- and (57)Co-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 [(64)Cu]Cu-ETS administration was compared to microsphere measurements of renal perfusion. The distribution and kinetics of [(64)Cu]Cu-ETS were further studied by PET imaging of the kidneys. The rate of [(64)Cu]Cu-ETS decomposition by blood was evaluated in vitro, employing octanol extraction to recover intact [(64)Cu]Cu-ETS.


RESULTS
The co-injected 11- and 15-microm 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. [(64)Cu]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 degrees C, the [(64)Cu]Cu-ETS radiopharmaceutical was observed to decompose with a half-time of 2.8 min.


CONCLUSIONS
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 [(60,61,62,64)Cu]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 [(60/61/62/64)Cu]Cu-ETS.
Green
Mark A
MA
Department of Industrial and Physical Pharmacy, Purdue University, West Lafayette, IN 47907-2091, USA. magreen@purdue.edu
Mathias
Carla J
CJ
Willis
Lynn R
LR
Handa
Rajash K
RK
Lacy
Jeffrey L
JL
Miller
Michael A
MA
Hutchins
Gary D
GD
D000818:Animals; D001783:Blood Flow Velocity / Q000502:physiology; D004353:Drug Evaluation, Preclinical; D005240:Feasibility Studies; D007090:Image Interpretation, Computer-Assisted / Q000379:methods; D007668:Kidney / Q000098:blood supply* / Q000000981:diagnostic imaging*; D009942:Organometallic Compounds / Q000493:pharmacokinetics; D049268:Positron-Emission Tomography / Q000379:methods*; D019275:Radiopharmaceuticals / Q000493:pharmacokinetics; D012077:Renal Artery / Q000000981:diagnostic imaging / Q000502:physiology*; D012079:Renal Circulation / Q000502:physiology*; D015203:Reproducibility of Results; D012680:Sensitivity and Specificity; D013552:Swine; D013882:Thiosemicarbazones / Q000493:pharmacokinetics
D009942:Organometallic Compounds; D019275:Radiopharmaceuticals; D013882:Thiosemicarbazones; C063294:copper (II) ethylglyoxal bis(N(4)-methylthiosemicarbazone)