title: Evaluation of copper(II)-pyruvaldehyde bis (N-4-methylthiosemicarbazone) for tissue blood flow measurement using 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.
authors.affiliation: Joint Department of Physics, Royal Marsden Hospital, Sutton, Surrey, UK.
authors.forename: H
authors.initials: H
authors.lastname: Young
authors.forename: P
authors.initials: P
authors.lastname: Carnochan
authors.forename: J
authors.initials: J
authors.lastname: Zweit
authors.forename: J
authors.initials: J
authors.lastname: Babich
authors.forename: S
authors.initials: S
authors.lastname: Cherry
authors.forename: R
authors.initials: R
authors.lastname: Ott
mesh_terms: D000818:Animals; D003037:Cobalt Radioisotopes; D003300:Copper; D003301:Copper Radioisotopes; D006801:Humans; D066298:In Vitro Techniques; D008863:Microspheres; D009942:Organometallic Compounds; D051381:Rats; D012039:Regional Blood Flow; D013882:Thiosemicarbazones; D014018:Tissue Distribution; D014055:Tomography, Emission-Computed
chemical_list: D003037:Cobalt Radioisotopes; D003301:Copper Radioisotopes; D009942:Organometallic Compounds; D013882:Thiosemicarbazones; C052629:copper pyruvaldehyde bis(N(4)-methylthiosemicarbazone) complex; D003300:Copper