Further observations upon the diagnosis of deafness in young children, with particular reference to the making of recommendations for special educational treatment.

Abstract

¹⁸F-MK-6240 is a highly selective, subnanomolar-affinity Positron Emission Tomography (PET) tracer for imaging neurofibrillary tangles (NFTs). Plasma kinetics, brain uptake, and preliminary quantitative analysis of ¹⁸F-MK-6240 in healthy elderly subjects (HE), subjects with clinically probable Alzheimer disease (AD), and amnestic mild cognitive impairment (MCI) were characterized in a first-in-human study. <b>Methods:</b> Dynamic PET scans of up to 150 min were performed in 4 cognitively normal HE, 4 AD and 2 MCI subjects, after bolus injection of 152-169 MBq ¹⁸F-MK-6240 to evaluate tracer kinetics and distribution in brain. Regional standardized uptake value ratio (SUVR) and distribution volume ratio (DVR) were determined using the cerebellar cortex as a reference region. Total distribution volume (<i>VT</i>) was assessed by compartmental modeling using radiometabolite corrected input function in a subgroup of 6 subjects. <b>Results:</b>¹⁸F-MK-6240 had rapid brain uptake with peak standardized uptake value of 3-5, followed by a uniformly quick washout from all brain regions in HE; slower clearance was observed in regions commonly associated with NFT deposition in AD. In AD, SUVR measured between 60-90 min postinjection was high (approximately 2-4) in regions associated with NFT deposition; whereas, in HE, SUVR was approximately 1 across all brain regions suggesting high tracer selectivity for binding NFTs in vivo. ¹⁸F-MK-6240 VT was approximately 2- to 3-fold higher in neocortical and medial temporal brain regions of AD compared with HE, and stabilized by 60 min in both groups. DVR estimated by Logan reference tissue model or compartmental modeling correlated well (R² &gt;0.9) to SUVR_{60-90 min} for AD. <b>Conclusion:</b>¹⁸F-MK-6240 exhibited favorable kinetics with high-binding levels to brain regions with a plausible pattern for NFT deposition in AD. In comparison, negligible tracer binding was observed in HE. This pilot study suggests simplified ratio methods such as SUVR can be employed to quantify NFT binding. These results support further clinical development of ¹⁸F-MK-6240 for potential application in longitudinal studies.