TY - JOUR T1 - <strong>Imaging of Mitochondrial Complex 1 with <sup>18</sup>F-BCPP-EF in the Healthy Human Brain</strong> JF - Journal of Nuclear Medicine JO - J Nucl Med SP - 1709 LP - 1709 VL - 59 IS - supplement 1 AU - Ayla Mansur AU - Robert Comley AU - Yvonne Lewis AU - Lefkos Middleton AU - Mickael Huiban AU - Qi Guo AU - Jan Passchier AU - Hideo Tsukada AU - Roger Gunn AU - Eugenii Rabiner AU - for the MIND MAPS CONSORTIUM Y1 - 2018/05/01 UR - http://jnm.snmjournals.org/content/59/supplement_1/1709.abstract N2 - 1709Objectives: Mitochondrial Complex 1 (MC1) availability has been quantified in the living brain using the novel radioligand [18F]BCPP-EF, in pre-clinical models of Alzheimer’s Disease (AD), Parkinson’s Disease(PD), ischemic insult and aging (Tsukada, Nishiyama, Ohba et al., 2014; Kanazawa et al., 2017; Tsukada, Ohba, Kanazawa, et al., 2014; Tsukada, Ohba, Nishiyama, et al., 2014). The successful translation of [18F]BCPP-EF as a tool for quantifying MC1 expression in the human brain, requires the determination of an appropriate kinetic modelling approach. In this study we have evaluated a range of modelling approaches to quantify MC1 in the healthy human brain. Methods: Eight healthy volunteers (ages 22-75) underwent a 90 minute dynamic [18F]BCPP-EF scan with arterial blood samples acquired during the scan to enable full quantification. A structural T1 MRI scan of the brain was acquired to allow delineation of anatomical regions of interest. A metabolite corrected arterial plasma input function and regional time activity curves (TACs) were derived from the arterial blood data and the [18F]BCPP-EF PET emission data respectively. Both the two-tissue compartmental model (2TCM) and the multilinear analysis 1 model (MA1) were applied to the data and the resultant model fits were evaluated in the cerebral white matter (CWM), frontal cortex (FCTX), striatum (STR), hippocampus (HIP) and substantia nigra (SN). Analyses of the PET data were performed using MIAKATTM software (version 4.3.1). A variety of outcome parameters including VT (volume of distribution), VT/fp (where fp is the free fraction of parent metabolite in plasma) and DVR (distribution volume ratio) were examined. DVR values were calculated using the region with the lowest VT values (CWM) as a pseudo-reference region. The relationship between these outcome parameters and subjects age were also evaluated. Results: [18F]BCPP-EF uptake was rapid in all regions and peaked between 10-20 minutes(Fig 1a,b), consistent with published preclinical data (Tsukada., 2014), followed by a gradual washout from all regions. Both 2TCM and MA1 produced good fits when applied to the TAC data. VT values estimated using both the 2TCM and MA1 models were lowest in the CWM and highest in the STR (Fig 1c), with VT2TCM values highly correlating with VTMA1 values (r = 0.99). VT / fp results mirrored the VT estimates with the highest values observed for the STR and lowest for the CWM (Fig 1d). DVR and VT showed a slight negative trend with increasing age in all regions analysed (STR: -0.05 VT/year, -0.003 DVR/year, p=0.77). Conclusion: [18F]BCPP-EF binding in the human brain is consistent with previously published non-human primate data (Tsukada et al, 2014). Kinetic modelling of the data using MA1 appears to be suitable for the quantification of [18F]BCPP-EF in the human brain. Effects of age on [18F]BCPP-EF binding appear to be modest. The low uptake and VT observed for the CWM region warrants further investigation into its potential use as a pseudo-reference region. ER -