AUTHOR=Silberbauer Leo R. , Gryglewski Gregor , Berroterán-Infante Neydher , Rischka Lucas , Vanicek Thomas , Pichler Verena , Hienert Marius , Kautzky Alexander , Philippe Cecile , Godbersen Godber M. , Vraka Chrysoula , James Gregory M. , Wadsak Wolfgang , Mitterhauser Markus , Hacker Marcus , Kasper Siegfried , Hahn Andreas , Lanzenberger Rupert 

TITLE=Serotonin Transporter Binding in the Human Brain After Pharmacological Challenge Measured Using PET and PET/MR

JOURNAL=Frontiers in Molecular Neuroscience

VOLUME=12

YEAR=2019

URL=https://www.frontiersin.org/journals/molecular-neuroscience/articles/10.3389/fnmol.2019.00172

DOI=10.3389/fnmol.2019.00172

ISSN=1662-5099

ABSTRACT=<p><bold>Introduction:</bold><italic>In-vivo</italic> quantification of the serotonin transporter (SERT) guided our understanding of many neuropsychiatric disorders. A recently introduced bolus plus constant infusion protocol has been shown to allow the reliable determination of SERT binding with reduced scan time. In this work, the outcomes of two methods, a bolus injection paradigm on a GE PET camera, and a bolus plus infusion paradigm on a combined Siemens PET/MR camera were compared.</p><p><bold>Methods:</bold> A total of seven healthy subjects underwent paired PET and paired PET/MR scans each with intravenous double-blind application of 7.5 mg citalopram or saline in a randomized cross-over study design. While PET scans were performed according to standard protocols and non-displaceable binding potentials (BP<sub>ND</sub>) were calculated using the multi-linear reference tissue model, during PET/MR measurements [<sup>11</sup>C]DASB was applied as bolus plus constant infusion, and BP<sub>ND</sub> was calculated using the steady state method and data acquired at tracer equilibrium. Occupancies were calculated as the relative decrease in BP<sub>ND</sub> between saline and citalopram scans.</p><p><bold>Results:</bold> During placebo scans, a mean difference in BP<sub>ND</sub> of −0.08 (−11.71%) across all ROIs was found between methods. PET/MR scans resulted in higher BP<sub>ND</sub> estimates than PET scans in all ROIs except the midbrain. A mean difference of −0.19 (−109.40%) across all ROIs between methods was observed for citalopram scans. PET/MR scans resulted in higher BP<sub>ND</sub> estimates than PET scans in all ROIs. For occupancy, a mean difference of 23.12% (21.91%) was observed across all ROIs. PET/MR scans resulted in lower occupancy compared to PET scans in all ROIs except the temporal cortex. While for placebo, BP<sub>ND</sub> of high-binding regions (thalamus and striatum) exhibited moderate reliability (ICC = 0.66), during citalopram scans ICC decreased (0.36–0.46). However, reliability for occupancy remained high (0.57–0.82).</p><p><bold>Conclusion:</bold> Here, we demonstrated the feasibility of reliable and non-invasive SERT quantification using a [<sup>11</sup>C]DASB bolus plus constant infusion protocol at a hybrid PET/MR scanner, which might facilitate future pharmacological imaging studies. Highest agreement with established methods for quantification of occupancy and SERT BP<sub>ND</sub> at baseline was observed in subcortical high-binding regions.</p>