QUANTIFICATION OF REGIONAL MYOCARDIAL PERFUSION WITH GENERATOR-PRODUCED CU-62-PTSM AND POSITRON EMISSION TOMOGRAPHY

Background. Noninvasive assessment of regional myocardial perfusion at rest and after stress is important for the objective evaluation of the effects of coronary artery disease and its response to therapy. Centers that do not have cyclotrons rely on generator-produced radioisotopes for assessment of regional myocardial perfusion with positron emission tomography (PET). The aim of the present study was to develop and implement an approach to quantify regional myocardial perfusion using copper(II) pyruvaldehyde bis-(N4-thiosemicarbazone) (PTSM) labeled with the generator-produced, positron-emitting radionuclide Cu-62 (t1/2=9.7 minutes). Methods and Results. Regional perfusion was estimated from dynamic PET scans after intravenous administration of Cu-62-PTSM in 21 studies in 13 intact dogs evaluated over a wide range of myocardial flow values. In 15 interventions in nine dogs, regional perfusion was also estimated with (H2O)-O-15. Regional perfusion with C-62-PTSM was estimated from dynamic blood and tissue time-activity curves, along with the model parameter k1 (forward rate of transport) and the PET parameter F(BM) (fraction of blood pool activity observed in tissue), using a two-compartment kinetic model. Arterial blood activity was corrected for red blood cell-associated Cu-62. In 44 comparisons, estimates of regional perfusion with Cu-62-PTSM correlated well with estimates obtained with concomitantly administered radiolabeled microspheres (y=0.90x+/-0.15, r=0.95, p<0.05) over a flow range from 0.23 to 6.14 ml/g per minute. In five healthy human volunteers evaluated at rest with (H2O)-O-15 and Cu-62-PTSM, regional perfusion estimated with (Cu-62-PTSM was not significantly different from that obtained with (H2O)-O-15 (1.05+/-0.36 versus 0.96+/-0.28 ml/g per minute). Cu-62-PTSM provided high-quality images of the heart. Conclusions. The results of this study demonstrate that quantification of regional myocardial perfusion is feasible using generator-produced Cu-62-PTSM. Since CU-62-PTSM can be used to estimate perfusion in the brain, kidney, and tumors as well as in the heart, it is an attractive tracer for centers that rely on generator-produced tracers for the evaluation of perfusion with PET.