¹²³I-Iofluopane Single-Photon Emission Computed Tomography as an Imaging Biomarker of Pre-Synaptic Dopaminergic...

Dopaminergic (DA) system function is frequently disrupted after traumatic brain injury (TBI). However, published interventions that target the DA system with the hope of enhancing functional outcomes are inconclusive, partially because of the lack of DA signaling biomarkers that can be used to select patients likely to benefit from DA-directed therapies or to monitor treatment efficacy. The aim of this study was to evaluate the feasibility of using ¹²³I-iofluopane single-photon emission computerized tomography (SPECT) to assess pre-synaptic DA system dysfunction after severe TBI. Eighteen patients with severe TBI were enrolled in this study. ¹²³I-iofluopane SPECT imaging was performed at baseline and again 2.5 h after a single dose of methylphenidate (MP) administered enterally. DA transporter (DAT) specific binding ratio (SBR) before and after MP was measured. Functional outcomes included the Disability Rating Scale, JFK Coma Recovery Scale-Revised, Functional Independence Measure, and Functional Assessment Measure. Thirteen of 18 patients completed the study. Average time from injury to SPECT scan was 48 days (standard deviation [SD], 24 days; median, 31). Baseline ioflupane striatal SBR was 1.51 ± 0.46 (median, 1.67). A 43.1% (SD, 16; median, 46.5) displacement of ioflupane from pre-synaptic DAT was observed after MP administration. Baseline SBR positively correlated with functional status at baseline and 4 weeks after completion of the study. Serum MP levels correlated with relative change in SBR (r_s = 0.60; p = 0.04). Our findings suggest that ¹²³I-iofluopane SPECT is a promising tool to determine the severity of pre-synaptic DA terminal disruption and for monitoring pharmacokinetics and pharmacodynamics of therapeutic interventions targeting the DA system.