Optimization of the radiosynthesis of [(18) F]MEFWAY for imaging brain serotonin 1A receptors by using the GE TracerLab FXFN-Pro module.

The aim of this study was to develop a highly reliable radiofluorination method for the preparation of N-{2-[4-(2-methoxyphenyl)piperazinyl]ethyl}-N-(2-pyridyl)-N-(4-(18) F-fluoromethylcyclohexane)carboxamide ([(18) F]Mefway) by using a fully automated system. The optimal condition is composed of two parts. The extraction system of the trapped F-18 in the anion exchange resin (i.e., quaternary methylamine cartridge) is a complex of Kryptofix 2.2.2. (K222, 4 mg/0.9 mL methanol) and K2 CO3 (1 mg/0.1 mL H2 O). After removing the solvents, the trans-tosylated Mefway precursor (1 mg/0.5 mL acetonitrile) was reacted with dried K222-K[(18) F] at 100°C for 5 min. After purification and formulation, [(18) F]Mefway was obtained with 38 ± 2.4% (decay corrected, n = 34) radiochemical yield, a total synthesis time of 52 ± 3.4 min, specific activity was 120.6 ± 8.7 GBq/µmol at the end of synthesis and a radiochemical purity of 99%. According to the quality control tests, formulated [(18) F]Mefway is suitable to apply parenteral clinical application.

Effective microPET imaging of brain 5-HT(1A) receptors in rats with [(18) F]MeFWAY by suppression of radioligand defluorination.

INTRODUCTION: [(18) F]MeFWAY has been developed for imaging the serotonin 1A receptors in the brain. The purpose of this study were to verify the metabolic stability of [(18) F]MeFWAY, to measure the degree of defluorination of [(18) F]MeFWAY in vivo, to investigate methods of inhibition of defluorination of [(18) F]MeFWAY, and to assess the efficacy of [(18) F]MeFWAY in rat brains in vivo. METHODS: MicroPET experiments in rats were conducted to confirm the distribution of radioactivity in the brain. Nondisplaceable binding potential (BP(ND) ) in the hippocampus and frontal cortex were also analyzed. Miconazole and fluconazole were tested for the ability to suppress defluorination of [(18) F]MeFWAY. We conducted a blockade and displacement experiment by treating with WAY-100635. RESULTS: In vitro stability tests showed that MeFWAY was very stable in serum for 6 h, but PET revealed that authentic [(18) F]MeFWAY underwent significant defluorination in vivo. In vitro inhibition study against decreasing parent activity in liver microsomes, miconazole and fluconazole suppressed metabolic elimination of MeFWAY. However, in the PET study, fluconazole showed more potent inhibitory activity than miconazole. In the suppression of metabolizing enzymes using fluconazole, radioactivity in skull was dramatically decreased by 81% (compared with 69% with miconazole) and it was coupled with an increase in brain uptake. Moreover, BP(ND) in hippocampus was 5.53 and 2.66 in frontal cortex. The blockade and displacement study showed the specificity of [(18) F]MeFWAY to 5-HT(1A) receptors. CONCLUSION: In the rat brain, [(18) F]MeFWAY microPET showed skull uptake due to defluorination in vivo. We can effectively overcome this drawback with fluconazole.

The Use of Dynamic Contrast-Enhanced Magnetic Resonance Imaging for the Evaluation of Blood-Brain Barrier Disruption in Traumatic Brain Injury: What Is the Evidence?

(1) Background: Blood brain barrier (BBB) disruption following traumatic brain injury (TBI) results in a secondary injury by facilitating the entry of neurotoxins to the brain parenchyma without filtration. In the current paper, we aimed to review previous dynamic contrast-enhanced magnetic resonance imaging (DCE-MRI) studies to evaluate the occurrence of BBB disruption after TBI. (2) Methods: In electronic databases (PubMed, Scopus, Embase, and the Cochrane Library), we searched for the following keywords: dynamic contrast-enhanced OR DCE AND brain injury. We included studies in which BBB disruption was evaluated in patients with TBI using DCE-MRI. (3) Results: Four articles were included in this review. To assess BBB disruption, linear fit, Tofts, extended Tofts, or Patlak models were used. KTrans and ve were increased, and the values of vp were decreased in the cerebral cortex and predilection sites for diffusion axonal injury. These findings are indicative of BBB disruption following TBI. (4) Conclusions: Our analysis supports the possibility of utilizing DCE-MRI for the detection of BBB disruption following TBI.

The blood-brain barrier disruption after syncope: a dynamic contrast-enhanced magnetic resonance imaging study: A case report.

RATIONALE: Using dynamic contrast-enhanced magnetic resonance imaging (DCE-MRI), we demonstrated blood-brain barrier (BBB) disruption following syncope. PATIENT CONCERNS: A 45-year-old man experienced syncope with a chief complaint of syncope (duration: 1 minutes), 1 day before visiting a university hospital for examination. He had no history of medical problems and was not taking any medications. This episode was the first in his lifetime. DIAGNOSES: After syncope, the patient did not have any illnesses or symptoms, such as headache, cognitive deficits, or somnolence. INTERVENTIONS: Cardiac evaluation did not reveal any abnormal findings. In addition, in conventional brain and chest computed tomography and brain MRI, no abnormal lesions were observed. OUTCOMES: DCE-MRI of the patient showed bright blue colored lines within the sulci throughout the cerebral cortex. The regions of interest, including bright blue colored lines, had significantly higher Ktrans values (6.86 times higher) than those in healthy control participants. These findings are indicative of BBB disruption of the vessels in the sulci. LESSONS: Using DCE-MRI, we demonstrated BBB disruption following syncope. DCE-MRI is a useful tool for the detection of BBB disruption following syncope.

Prognostic Factors of Atypical Meningioma: Overall Survival Rate and Progression Free Survival Rate.

OBJECTIVE: Atypical meningioma is rare tumor and there is no accurate guide line for optimal treatment. This retrospective study analyzed the prognostic factors, the effect of different methods of treatments and the behavior of atypical meningioma. METHODS: Thirty six patients were diagnosed as atypical meningioma, among 273 patients who were given a diagnosis of meningioma in the period of 2002 to 2015. Age, gender, tumor location, Ki 67, Simpson grade and treatment received were analyzed. We studied the correlation between these factors with recurrence, overall survival rate and progression free survival. RESULTS: Median overall survival time and progression free survival time are 60 and 53 (months). Better survival rate was observed for patients less than 50 years old but with no statistical significance (p=0.322). And patients with total resection compared with subtotal resection also showed better survival rate but no statistical significance (p=0.744). Patients with a tumor located in skull base compared with patients with a tumor located in brain convexity and parasagittal showed better progression free survival (p=0.048). Total resection is associated with longer progression-free survival than incomplete resection (p=0.018). CONCLUSION: We confirmed that Simpson grade was significant factor for statistically affect to progression free survival in univariate analysis. In case of skull base atypical tumor, it is analyzed that it has more recurrence than tumor located elsewhere. Overall survival was not affected statistically by patient age, gender, tumor location, Ki 67, Simpson grade and treatment received in this study.

Dopaminergic neuron destruction reduces hippocampal serotonin 1A receptor uptake of trans-[(18)F]Mefway.

The purpose of the present study is to investigate the relationship between dopaminergic neuron destruction and 5-HT system changes in a hemiparkinsonian rat model. We performed PET imaging studies with trans-[(18)F]Mefway in a hemiparkinsonian model of unilateral 6-hydroxydopamine (6-OHDA) rats. Region-of-interests (ROIs) were drawn in the hippocampus (HP) and cerebellum (CB). HP uptake, the ratios of specific binding to non-specific binding in the HP, and non-displaceable binding potential (BPND) in the HP were compared between 6-OHDA and control rats. As a result, unilateral 6-OHDA-lesioned rats exhibited significant bilateral reduction of HP uptake and trans-[(18)F]Mefway BPND compared to the intact control group. Therefore, the results demonstrate that destruction of the dopaminergic system causes the reduction of the serotonergic system.