Head-to-head comparison of [18F]-Flortaucipir, [18F]-MK-6240 and [18F]-PI-2620 postmortem binding across the spectrum of neurodegenerative diseases.

We and others have shown that [18F]-Flortaucipir, the most validated tau PET tracer thus far, binds with strong affinity to tau aggregates in Alzheimer's (AD) but has relatively low affinity for tau aggregates in non-AD tauopathies and exhibits off-target binding to neuromelanin- and melanin-containing cells, and to hemorrhages. Several second-generation tau tracers have been subsequently developed. [18F]-MK-6240 and [18F]-PI-2620 are the two that have garnered most attention. Our recent data indicated that the binding pattern of [18F]-MK-6240 closely parallels that of [18F]-Flortaucipir. The present study aimed at the direct comparison of the autoradiographic binding properties and off-target profile of [18F]-Flortaucipir, [18F]-MK-6240 and [18F]-PI-2620 in human tissue specimens, and their potential binding to monoamine oxidases (MAO). Phosphor-screen and high resolution autoradiographic patterns of the three tracers were studied in the same postmortem tissue material from AD and non-AD tauopathies, cerebral amyloid angiopathy, synucleopathies, transactive response DNA-binding protein 43 (TDP-43)-frontotemporal lobe degeneration and controls. Our results show that the three tracers show nearly identical autoradiographic binding profiles. They all strongly bind to neurofibrillary tangles in AD but do not seem to bind to a significant extent to tau aggregates in non-AD tauopathies pointing to their limited utility for the in vivo detection of non-AD tau lesions. None of them binds to lesions containing ß-amyloid, α-synuclein or TDP-43 but they all show strong off-target binding to neuromelanin and melanin-containing cells, as well as weaker binding to areas of hemorrhage. The autoradiographic binding signals of the three tracers are only weakly displaced by competing concentrations of selective MAO-B inhibitor deprenyl but not by MAO-A inhibitor clorgyline suggesting that MAO enzymes do not appear to be a significant binding target of any of them. These findings provide relevant insights for the correct interpretation of the in vivo behavior of these three tau PET tracers.

Trends in hospitalization and death rates among patients with head and neck cancer in Spain, 2009 to 2019.

BACKGROUND: Head and neck squamous cell carcinoma (HNSCC) is the seventh most common cancer worldwide, and prevalence is still substantially higher in men than in women. Causative factors include smoking and alcohol use, while human papillomavirus (HPV) infection is causally related to a subset of oropharyngeal cancers. In this retrospective study, we aimed to provide estimates on the clinical and economic burden of HNSCC in Spain. METHODS: We used the discharge reports from the Spanish Minimum Basic Data Set (MBDS), to retrospectively analyze hospital discharge data in individuals with a diagnosis of HNSCC in any diagnostic position, based on the ICD coding system (ICD-9-CM and ICD10 CM), from 2009 to 2019. RESULTS: A total of 175,340 admissions and 14,498 deaths due to laryngeal, pharyngeal and oral cavity cancer were recorded in Spain, of which 85% occurred in men. The most prevalent diagnoses were laryngeal cancer in men (50.9%) and oral cavity cancer in women (49.1%). In general, the hospitalization and death rates for all major head and neck cancer sites decreased in men and increased or remained stable in women during the study period. However, the corresponding rates for tonsil cancer, strongly associated with HPV infection, increased significantly in men. Overall, the economic burden of HNSCC during the study period was estimated at 100 million euros per year on average. CONCLUSION: HNSCC still places an important clinical and economic burden on the health system in Spain. Prevention strategies should be prioritized, and vaccination programs against HPV in both sexes should be reinforced.