Surrogate markers for cerebral blood flow correlate with [18F]-fallypride binding potential at dopamine D2/3 receptors in human striatum

Positron emission tomography (PET) with the high affinity dopamine D2/3 receptor ligand [18F]-fallypride affords estimates of the binding potential (BPND) in extra-striatal regions of low receptor abundance, but the sufficient recording time for accurate measurements in striatum has been called into question. We have earlier argued that transient equilibrium measurements are obtained in striatum with [18F]-fallypride PET recordings of 3 h duration, which may be the practical limit for clinical investigations without interrupted scanning. However, the high extraction fraction of [18F]-fallypride predicts flow-dependence of tracer delivery to brain, which may be a source of variance of the apparent BPND in regions of high binding. To test this prediction, we conducted a retrospective analysis of [18F]-fallypride PET data from a group of 50 healthy volunteers (age 1858 years [mean +/- SD: 32.6 +/- 10.6), who had participated in clinical studies without arterial input measurements. We used the initial 120-s integral (AUC) of the venous confluence (VC) as a surrogate marker for cerebral blood flow (CBF) and tested for correlations between regional estimates of BPND calculated by the simplified reference tissue model (SRTM) and the individual VC-AUC. The magnitude of BPND in a high binding region (putamen), but not in a low binding region (thalamus) correlated positively with VC-AUC, suggesting that approximately 9% of the variance in the [18F]-fallypride BPND in putamen can be attributed to individual differences in this surrogate marker for CBF, a contribution equal in magnitude to the effects of age on BPND in putamen of the present healthy control group. Synapse, 2013. (c) 2012 Wiley Periodicals, Inc.