Measurement of regional cerebral blood flow with copper-62-PTSM and a three-compartment model

We evaluated quantitatively 62Cu-labeled pyruvaldehyde bis(N4-methylthiosemicarbazone) copper II (62Cu-PTSM) as a brain perfusion tracer for positron emission tomography (PET). For quantitative measurement, the octanol extraction method is needed to correct for arterial radioactivity in estimating the lipophilic input function, but the procedure is not practical for clinical studies. To measure regional cerebral blood flow (rCBF) by 62Cu-PTSM with simple arterial blood sampling, a standard curve of the octanol extraction ratio and a three-compartment model were applied.

We performed both 15O-labeled water PET and 62 Cu-PTSM PET with dynamic data acquisition and arterial sampling in six subjects. Data obtained in 10 subjects studied previously were used for the standard octanol extraction curve. Arterial activity was measured and corrected to obtain the true input function using the standard curve.

Graphical analysis (Gjedde-Patlak plot) with the data for each subject fitted by a straight regression line suggested that 62Cu-PTSM can be analyzed by the three-compartment model with negligible K4. Using this model, K1-K3 were estimated from curve fitting of the cerebral time-activity curve and the corrected input function. The fractional uptake of 62Cu-PTSM was corrected to rCBF with the individual extraction at steady state calculated from K1-K3. The influx rates (Ki) obtained from three-compartment model and graphical analyses were compared for the validation of the model. A comparison of rCBF values obtained from 62Cu-PTSM and 150-water studies demonstrated excellent correlation.

The results suggest the potential feasibility of quantitation of cerebral perfusion with 62Cu-PTSM accompanied by dynamic PET and simple arterial sampling.