Evaluation of copper(II)-pyruvaldehyde bis (N-4-methylthiosemicarbazone) for tissue blood flow measurement usina a trapped tracer model

Abstract

Copper(II)-pyruvaldehyde bis (N-4-methylthiosemicarbazone) (Cu-PTSM) labelled with ^62,64Cu is a promising radiotracer for the study of blood flow using positron emission tomography (PET). We have investigated the application of a simple trapped tracer model to measurements of tissue ⁶⁴Cu-PTSM uptake combined with continuous arterial sampling. A dual-tracer method was used to compare blood flow estimated by ⁶⁴Cu-PTSM with values derived from measurements using cobalt-57 microspheres in the rat. Prolonged retention of ⁶⁴Cu-PTSM following intravenous administration was initially confirmed in both normal tissues and tumours. After intraventricular ⁶⁴Cu-PTSM infusion, cumulative arterial ⁶⁴Cu activity increased progressively, and after extraction in n-octanol was found to plateau to levels corresponding with those reached following administration of ⁵⁷CO microspheres. Rapid and species-dependent rates of ⁶⁴Cu-PTSM decomposition to non-extractable ⁶⁴Cu complexes were found in rat and human blood in vitro (70%±6% and 43%±5% respectively at 16 min), demonstrating the need for immediate processing of arterial samples. Close agreement was found between blood flow estimated by ⁶⁴Cu-PTSM and ⁵⁷CO microsphere methods in tissues of low to moderate flow: muscle (0.01, 0.08, 0.07 ml/min per gram; mean difference, mean ⁶⁴Cu, mean ⁵⁷Co), brain (0.09, 0.52, 0.43 ml/min per gram) and kidney (−0.16, 2.29, 2.45 ml/min per gram). Estimates of cardiac output also compared favourably between the two methods (5.7, 59.8, 54.1 ml/min). We conclude that a simple tissue trapping model may be suitable for the derivation of blood flow estimates using ^62,64Cu-PTSM, PET imaging and continuous arterial blood sampling.