Confirmation of Specific Binding of the 18-kDa Translocator Protein (TSPO) Radioligand [18F]GE-180: a Blocking Study Using XBD173 in Multiple Sclerosis Normal Appearing White and Grey Matter

• DOI: 10.1007/s11307-019-01323-8
• Publication Date: 2019-02-22T10:35:48Z
• Authors: Sujata Sridharan; Joel Raffel; Ashwini Nandoskar; Chris Record; David J. Brooks; David Owen; David Sharp; Paolo A. Muraro; Roger Gunn; Richard Nicholas
• Keywords: Translocator protein; Radioligand; Binding potential

Measurements of non-displaceable binding (VND) positron emission tomography (PET) ligands are not often made in vivo humans because they require to displace target receptors and there few readily available, safe ones use. A technique measure VND for the 18-kDa translocator protein (TSPO) has recently been developed which compares total volume distribution (VT) before after administration TSPO ligand XBD173. Here, we used XBD173 with an occupancy plot quantify two radiotracers, [18F]GE-180 [11C]PBR28, cohorts people multiple sclerosis (MS). Additionally, compared plots subjects carrying high (HAB) or mixed (MAB) affinity polymorphisms estimate without receptor blockade. Twelve MS underwent baseline MRI 90-min dynamic PET [11C]PBR28 (n = 6; three HAB, MAB each). Arterial blood sampling was generate plasma input functions two-tissue compartment model. calculated using independent methods: (by modelling differences signal post XBD173) polymorphism across presence absence rs6971 genotypes). Whole brain VT (mean ± standard deviation) 0.29 0.17 ml/cm3 5.01 1.88 [11C]PBR28. Using respectively, 0.11 (95 % CI 0.02, 0.16) 0.20 (0.16, 0.34), accounting for, on average, 55 whole brain. For these values were 3.81 (3.02, 4.21) 3.49 (1.38, 4.27), 67 average VT. Although is low, indicating low penetration, half shown by reflected specific binding. higher thirds non-specific. No ROIs devoid signal, further confirming that true reference tissue approaches potentially problematic estimating levels.