title: Surrogate markers for cerebral blood flow correlate with [¹⁸F]-fallypride binding potential at dopamine D(2/3) receptors in human striatum.
abstract: Positron emission tomography (PET) with the high affinity dopamine D(2/3) receptor ligand [¹⁸F]-fallypride affords estimates of the binding potential (BP(ND) ) 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 BP(ND) 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 18-58 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 BP(ND) calculated by the simplified reference tissue model (SRTM) and the individual VC-AUC. The magnitude of BP(ND) 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 BP(ND) 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 BP(ND) in putamen of the present healthy control group.
authors.affiliation: Department of Nuclear Medicine, Ludwig-Maximilian University, Munich, Germany.
authors.forename: Paul
authors.initials: P
authors.lastname: Cumming
authors.forename: Guoming
authors.initials: G
authors.lastname: Xiong
authors.forename: Christian
authors.initials: C
authors.lastname: la Fougère
authors.forename: Axel
authors.initials: A
authors.lastname: Rominger
authors.forename: Peter
authors.initials: P
authors.lastname: Bartenstein
authors.forename: Hans-Georg
authors.initials: HG
authors.lastname: Buchholz
authors.forename: Markus
authors.initials: M
authors.lastname: Piel
authors.forename: Frank
authors.initials: F
authors.lastname: Rösch
authors.forename: Gerhard
authors.initials: G
authors.lastname: Gründer
authors.forename: Ingo
authors.initials: I
authors.lastname: Vernaleken
mesh_terms: D000293:Adolescent; D000328:Adult; D001549:Benzamides / Q000493:pharmacokinetics*; D001921:Brain / Q000000981:diagnostic imaging* / Q000378:metabolism; D002560:Cerebrovascular Circulation / Q000502:physiology*; D005260:Female; D005462:Fluorine Radioisotopes / Q000493:pharmacokinetics*; D006801:Humans; D008297:Male; D008875:Middle Aged; D049268:Positron-Emission Tomography; D017448:Receptors, Dopamine D2 / Q000378:metabolism*; D050637:Receptors, Dopamine D3 / Q000378:metabolism*; D012189:Retrospective Studies; D055815:Young Adult
chemical_list: D001549:Benzamides; C493593:DRD3 protein, human; D005462:Fluorine Radioisotopes; D017448:Receptors, Dopamine D2; D050637:Receptors, Dopamine D3; C574003:fallypride