Longitudinal changes in 18 F-THK5351 positron emission tomography in corticobasal syndrome.

BACKGROUND AND PURPOSE: Corticobasal syndrome (CBS) is pathologically characterized by tau deposits in neuronal and glial cells and by reactive astrogliosis. In several neurodegenerative disorders, 18 F-THK5351 has been observed to bind to reactive astrocytes expressing monoamine oxidase B. In this study, the aim was to investigate the progression of disease-related pathology in the brains of patients with CBS using positron emission tomography with 18 F-THK5351. METHODS: Baseline and 1-year follow-up imaging were acquired using magnetic resonance imaging and positron emission tomography with 18 F-THK5351 in 10 subjects: five patients with CBS and five age-matched normal controls (NCs). RESULTS: The 1-year follow-up scan images revealed that 18 F-THK5351 retention had significantly increased in the superior parietal gyrus of the patients with CBS compared with the NCs. The median increases in 18 F-THK5351 accumulation in the patients with CBS were 6.53% in the superior parietal gyrus, 4.34% in the precentral gyrus and 4.33% in the postcentral gyrus. In contrast, there was no significant increase in the regional 18 F-THK5351 retention in the NCs. CONCLUSIONS: Longitudinal increases in 18 F-THK5351 binding can be detected over a short interval in the cortical sites of patients with CBS. A monoamine oxidase B binding radiotracer could be useful in monitoring the progression of astrogliosis in CBS.

Tau imaging with [18 F]THK-5351 in progressive supranuclear palsy.

BACKGROUND AND PURPOSE: Visualization of pathogenic protein aggregates is crucial to elucidate pathomechanisms and to make an accurate diagnosis in many neurodegenerative conditions. Aggregates of the microtubule-binding protein, tau, are one of the most important pathogenic molecules in neurodegenerative disorders. Progressive supranuclear palsy (PSP) is characterized by the deposition of tau proteins in some specific area such as the basal ganglia and brainstem. We tried to detect tau lesions in the brains of living patients with PSP with a novel positron emission tomography (PET) tracer, [18 F]THK-5351, which we have recently developed. METHODS: Paraffin-embedded brain sections of the patients with PSP were used for autoradiography with [3 H]THK-5351 and immunohistochemistry. Nine healthy controls, 13 patients with Alzheimer's disease and three patients with PSP participated in this PET study with [18 F]THK-5351. To detect amyloid-ß deposition, PET imaging with Pittsburgh compound B was also performed. RESULTS: Autoradiography in the brain sections of patients with PSP demonstrated [3 H]THK-5351 binding to tau deposits with a high selectivity. Although patients with PSP exhibited no remarkable [18 F]THK-5351 retention in the temporal cortex, significantly higher tracer retention was observed in the globus pallidus and midbrain. In contrast, amyloid imaging with Pittsburgh compound B showed no remarkable accumulation in the cerebral cortex of PSP. CONCLUSIONS: We conclude that [18 F]THK-5351 PET can potentially be used to detect the regional brain distribution of tau lesions in PSP, thereby facilitating the differential diagnosis of neurodegenerative disorders associated with tau protein.

Performance evaluation of the small-animal PET scanner ClairvivoPET using NEMA NU 4-2008 Standards.

The aim of this study was to evaluate the performance of ClairvivoPET using NEMA NU4 standards. The ClairvivoPET incorporates a LYSO dual depth-of-interaction detector system with 151 mm axial field of view (FOV). Spatial resolution, sensitivity, counting rate capabilities, and image quality were evaluated using NEMA NU4-2008 standards. Normal mouse imaging was also performed for 10 min after intravenous injection of (18)F(-)-NaF. Data were compared with 19 other preclinical PET scanners. Spatial resolution measured using full width at half maximum on FBP-ramp reconstructed images was 2.16 mm at radial offset 5 mm of the axial centre FOV. The maximum absolute sensitivity for a point source at the FOV centre was 8.72%. Peak noise equivalent counting rate (NECR) was 415 kcps at 14.6 MBq ml(-1). The uniformity with the image-quality phantom was 4.62%. Spillover ratios in the images of air and water filled chambers were 0.19 and 0.06, respectively. Our results were comparable with the 19 other preclinical PET scanners based on NEMA NU4 standards, with excellent sensitivity because of the large FOV. The ClairvivoPET with iterative reconstruction algorithm also provided sufficient visualization of the mouse spine. The high sensitivity and resolution of the ClairvivoPET scanner provided high quality images for preclinical studies.

Voyage au bout de la nuit: Aß and tau imaging in dementias.

The last decade has witnessed the development and characterization of tracers for the evaluation of neuropathology in vivo. The introduction of these tracers, namely ß-amyloid (Aß) and later tau, are providing the tools to change the landscape and refine our understanding of Aß and tau deposition in the brain, allowing to investigate the causes, refine diagnosis and improve treatment of major neurodegenerative conditions such as Alzheimer's disease (AD), chronic traumatic encephalopathy (CTE) and frontotemporal lobar degeneration (FTLD). Aß and tau imaging allow examination of the regional and global changes of these disease markers over time as well as their relationship with other relevant parameters such as cognitive performance and neurodegenerative changes. Aß and tau imaging will enable to establish the role Aß and tau play -and interplay- in aging and disease. Aß and tau imaging value resides in being not only diagnostic, prognostic or progression markers, but also surrogate markers of disease, crucial for patient recruitment and efficacy evaluation of disease-specific therapies.

Automated preparation of hypoxic cell marker [18F]FRP-170 by on-column hydrolysis.

An automated synthesis for the preparation of the novel hypoxic cell marker, [(18)F]FRP-170 3, [(18)F]1-[2-fluoro-1-(hydroxymethyl)ethoxy]methyl-2- nitroimidazole, was developed using an on-column basic-hydrolysis step. The (18)F-labeled protected intermediate 2 was retained on a Sep-Pak Plus C18 cartridge and, in the same cartridge at room temperature, hydrolyzed by NaOH for deacetylation to give [(18)F]FRP-170. The elution method from the cartridge was optimized for direct injection of the crude product into an HPLC column. Thus, [(18)F]FRP-170 was prepared in 20-30% decay-corrected radiochemical yield within 60 min.

Functional anatomy of GO/NO-GO discrimination and response selection--a PET study in man.

The purpose of this study was to identify the functional fields activated in relation to the NO-GO decision. Nine healthy subjects participated in the study which consisted of two test positron emission tomography (PET) scans (GO/NO-GO task and response selection task) and one control scan. In the response selection task, subjects were asked to flex their thumb of the right hand when a light emitting diode (LED) placed 60 cm from their eyes turned on red and to flex their index finger of the right hand when LED turned on green. In the GO/NO-GO task, subjects were asked to flex their thumb when the LED turned on red, however, they were asked not to move their fingers when LED turned on green. In the control state, they were asked simply to look at the LED without any movement of finger during the course of the scan. The mean regional cerebral blood flow (rCBF) change images for each task minus control and task minus task were calculated and fields of significant rCBF changes were identified. Several fields in the prefrontal cortex of the right hemisphere were specifically activated in relation to the GO/NO-GO task. The results indicate that the prefrontal cortex of the right hemisphere may be a key structure to make a decision not to move.

Changes in regional cerebral blood flow during self-paced arm and finger movements. A PET study.

The purpose of this study was to identify the functional fields activated in relation to the self-paced proximal and distal arm movements. The regional cerebral blood flow (rCBF) was measured with positron emission tomography (PET) and 15O-labelled H2O (H2(15)O) in eight healthy subjects. All subjects performed the following three tasks: (1) repetitive opposition of thumb and index finger of the right hand, (2) repetitive co-contraction of biceps and tricepts brachii muscles of the right arm, and (3) rest. The mean rCBF change images for each task minus control was calculated and fields of significant rCBF changes were identified. Each movement activated different fields in the primary motor area (MI), the dorsal aspect of the premotor area (PMA) and the superior part of the prefrontal area (PFA) of the contralateral hemisphere. In these areas, arm fields were located relatively dorsally to the finger fields. In addition, specific fields in the ventral part of the PMA, the supplementary motor area (SMA), the superior parietal lobule (SPL) of the contralateral hemisphere, and the ipsilateral PFA were consistently activated during both movements. Due to a limited a field of view of the PET scanner in the axial direction, the PET scan could not cover the cerebellum. The results indicate that there may be somatotopical organization not only in the MI but also in the dorsal part of the PMA and the PFA, and that the specific fields in the ventral part of the PMA, the SMA, the SPL, and the PFA may be involved in self-paced movement.

Activity in the human primary motor cortex related to arm and finger movements.

With the purpose of mapping representations of the finger and proximal arm in the human primary motor cortex (MI), we measured regional cerebral blood flow (rCBF) in eight right-handed normal volunteers during self-paced finger and proximal arm movements. Each movement activated two different fields in MI, one located deep in the anterior lip of the central sulcus and the other relatively close to the surface of the precentral gyrus. Arm fields were located higher than finger fields. A superficial arm field and a deep finger field partially, overlapped. The results indicate that there are two spatially separate motor representations of the finger and proximal arm in the human MI.