A 26-year-old woman with relapsing-remitting multiple sclerosis (MS) underwent 18F-THK5351 PET during a remission period. PET imaging showed that small regions with elevated uptake of 18F-THK5351 were scattered in the brain and that the foci of 18F-THK5351 accumulations corresponded anatomically to MS plaques identified by MRI. Because 18F-THK5351 binds to monoamine oxidase B highly expressed in astrocytes, 18F-THK5351 accumulates in lesions undergoing astrogliosis. Hence, elevated uptake of 18F-THK5351 in the present case can represent ongoing astrogliosis in inactive MS lesions (plaques).

A BS TRACT: Background: We recently developed a positron emission tomography (PET) probe, [ 18 F]PM-PBB3, to detect tau lesions in diverse tauopathies, including mixed three-repeat and four-repeat (3R + 4R) tau fibrils in Alzheimer's disease (AD) and 4R tau aggregates in progressive supranuclear palsy (PSP). For wider availability of this technology for clinical settings, biasfree quantitative evaluation of tau images without a priori disease information is needed. Objective: We aimed to establish tau PET pathology indices to characterize PSP and AD using a machine learning approach and test their validity and tracer capabilities. Methods: Data were obtained from 50 healthy control subjects, 46 patients with PSP Richardson syndrome, and 37 patients on the AD continuum. Tau PET data from 114 regions of interest were subjected to Elastic Net cross-validation linear classification analysis with a oneversus-the-rest multiclass strategy to obtain a linear function that discriminates diseases by maximizing the area under the receiver operating characteristic curve.We defined PSP-and AD-tau scores for each participant as values of the functions optimized for differentiating PSP (4R) and AD (3R + 4R), respectively, from others. Results: The discriminatory ability of PSP-and AD-tau scores assessed as the area under the receiver operating characteristic curve was 0.98 and 1.00, respectively. PSPtau scores correlated with the PSP rating scale in patients with PSP, and AD-tau scores correlated with Mini-Mental State Examination scores in healthy control-AD continuum patients. The globus pallidus and amygdala were highlighted as regions with high weight coefficients for determining PSP-and AD-tau scores, respectively. Conclusions: These findings highlight our technology's unbiased capability to identify topologies of 3R + 4R versus 4R tau deposits.

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Background 18 F-THK5351 was recently shown to bind to monoamine oxidase B (MAO-B) with high affinity. MAO-B is highly concentrated in astrocytes and increases during astrogliosis. Therefore, 18 F-THK5351 accumulates in lesions undergoing astrogliosis. Cerebral infarction causes astrogliosis, which may be beneficial for repairing and regenerating injured cells and tissues in the lesions. Therefore, monitoring the degree of astrogliosis and stroke symptoms is essential for understanding the roles of astrogliosis in cerebral infarction. Case presentation A 72-year-old man, complaining of total loss of sensation in the left index finger, was diagnosed with acute cerebral infarction, and underwent 18 F-THK5351 positron emission tomography (PET) on two occasions after the stroke. The first PET scan performed on day 27 revealed intense uptake in the infarct lesion located around the right precentral and postcentral gyri. However, the second PET scan on day 391 showed that the uptake had diminished significantly. The sensory deficit in the left index finger had improved by 30 and 70% at the times of the first and second PET scans, respectively. Conclusions 18 F-THK5351 uptake in the infarct lesion evidently changed between days 27 and 391, along with improved sensory deficit in the left index finger. Astrocytes reportedly play a role in restoring neuronal integrity. Therefore, the temporal course of astrogliosis may have been related to improving stroke symptoms in this patient, suggesting that the degree of astrogliosis in the infarct lesion may aid in assessing the prognosis in stroke patients.