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

Introduction: In-vivo 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. Methods: 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_ND) were calculated using the multi-linear reference tissue model, during PET/MR measurements [¹¹C]DASB was applied as bolus plus constant infusion, and BP_ND was calculated using the steady state method and data acquired at tracer equilibrium. Occupancies were calculated as the relative decrease in BP_ND between saline and citalopram scans. Results: During placebo scans, a mean difference in BP_ND of -0.08 (-11.71%) across all ROIs was found between methods. PET/MR scans resulted in higher BP_ND 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_ND 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_ND 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). Conclusion: Here, we demonstrated the feasibility of reliable and non-invasive SERT quantification using a [¹¹C]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_ND at baseline was observed in subcortical high-binding regions.