Non-invasive kinetic modelling of PET tracers with radiometabolites using a constrained simultaneous estimation method: evaluation with 11C-SB201745

Background: Kinetic analysis of dynamic PET data requires an accurate knowledge of available PET tracer concentration within blood plasma over time, known as the arterial input function (AIF). The gold standard method used to measure the AIF requires serial arterial blood sampling over the course of the PET scan, which is an invasive procedure and makes this method less practical in clinical settings. Traditional image-derived methods are limited to specific tracers and are not accurate if metabolites are present in the plasma. Results: In this work, we utilise an image-derived whole blood curve measurement to reduce the computational complexity of the simultaneous estimation method (SIME), which is capable of estimating the AIF directly from tissue time activity curves (TACs). This method was applied to data obtained from a serotonin receptor study (C-11-SB207145) and estimated parameter results are compared to results obtained using the original SIME and gold standard AIFs derived from arterial samples. Reproducibility of the method was assessed using test-retest data. It was shown that the incorporation of image-derived information increased the accuracy of total volume of distribution (V-T) estimates, averaged across all regions, by 40% and non-displaceable binding potential (BPND) estimates by 16% compared to the original SIME. Particular improvements were observed in K-1 parameter estimates. BPND estimates, based on the proposed method and the gold standard arterial sample-derived AIF, were not significantly different (P = 0.7). Conclusions: The results of this work indicate that the proposed method with prior AIF information obtained from a partial volume corrected image-derived whole blood curve, and modelled parent fraction, has the potential to be used as an alternative non-invasive method to perform kinetic analysis of tracers with metabolite products.