• Microbiology and Biotechnology Letters
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• v.31 no.4
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• pp.377-382
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• 2003

Purification of methioninase resulted in a yield of 69%, and SDS-PAGE analysis of the purified product revealed a single band of approximately 43 kDa in molecular weight. in vitro experiments with cancer cells incubated in methionine-free media demonstrated an increase in $^{11}$ C-methionine uptake to 25.8$\pm$1.1% at 6 hr, 31.8$\pm$0.8% at 24 hr, and 62.2$\pm$0.6% at 48hr, compared to controls. Treatment of the cancer cells with purified methioninase showed no decrease in survival after a 2 hr incubation with 0.01 U/ml, but survival of RR1022 cells decreased 30% after 24 to 48 hr incubation. SKOV-3 cells showed a 5% and 14% decrease in survival with 0.1 and 1 U/ml methioninase after 24 hr. After 48hr survival decreased 15% and 24% with 0.1 and 1 U/ml methioninase. Measurements of $^{11}$ C-methionine uptake in RR1022 cells demonstrated no change at 2 hr, but a 13.7$\pm$4.7% and 40.7$\pm$2.6% increase in uptake at 24 and 48 hr, respectively. SKOV-3 cells also showed no change at 2 hr, but had a 17.7$\pm$7.2% and 38.9$\pm$4.9% increase in $^{11}$ C-methionine uptake after 24 hr and 48 hr treatment with methioninase, respectively. $^{11}$ C-methionine PET imaging revealed clear visualization of both the tumors and contralateral infectious lesions. Administration of rMET appeared to result in a slight increase in tumor:nontumor contrast on $^{11}$ C-methionine PET images. Injection of purified methioninase also produced PET images where tumor uptake was higher than that of infectious lesions.

• The Korean Journal of Nuclear Medicine Technology
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• v.12 no.3
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• pp.181-183
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• 2008

We developed simple and highly efficient synthesis method for [$^{11}C$]methionine using solid-phase extraction method. For synthesis, we used C18 cartridge. [$^{11}C$]methionine was synthesized on C18 cartridge according to the solid-phase [$^{11}C$]methylation of precursor L-homocysteine thiolactone hydrochloride. The radiochemical yields of [$^{11}C$]methionine was $48.9{\pm}7.93%$ decay corrected (results of 30 syntheses, mean$\pm$SD), with average production higher than 180 mCi. This procedure showed high yield and simple synthesis of [$^{11}C$]methionine.

• Journal of Radiopharmaceuticals and Molecular Probes
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• v.2 no.2
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• pp.123-131
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• 2016

Increasing clinical demand for carbon-11 labeled radiopharmaceuticals has triggered technological advances in fields of radiochemistry and automated modules. Even though carbon-11 has a short half-life ($t_{1/2}=20.4min$), the consecutive second production of carbon-11 labeled radiopharmaceutical in one $^{11}C$-synthetic module should be delayed at least over 4 h to avoid the high radiation exposure. We herein aimed to produce two different carbon-11 labeled radiopharmaceuticals ([$^{11}C$]PIB and [$^{11}C$]methionine) by sharing of [$^{11}C$]methylation source in one $^{11}C$-synthetic module. The synthesis of $^{11}C$-labeling reagents ($[^{11}C]CH_3I$ or $[^{11}C]CH_3OTf$) is fully automated using the commercial TRACERlab $FX_{C-pro}$ module and is readily adaptable to $^{11}C$-labeling reactor for [$^{11}C$]PIB as well as another $^{11}C$-labeling apparatus for [$^{11}C$]methionine via the three-way valve. After completing the [$^{11}C$]PIB production, the re-synthesized $[^{11}C]CH_3I$ was passed through the three-way valve connected the polyetheretherketone (PEEK) line and loaded into the C18 Sep-Pak cartridge including the methionine precursor. The labeled product [^${11}C$]methionine was purified by a simple cartridge separation and reformulated into saline. The radiochemical yield of [$^{11}C$]PIB and [$^{11}C$]methionine were $5.3{\pm}0.6%$ and $18.7{\pm}0.8%$ (n.d.c.), respectively, with over 97% of radiochemical purity. The specific activity of [$^{11}C$]PIB was over $110GBq/{\mu}mol$. Total production time of two radiopharmaceuticals needs about 2 h from $1^{st}$ beam irradiation including quality control tests. Final [$^{11}C$]PIB and [$^{11}C$]methionine were satisfied all quality control test standards.

• The Korean Journal of Nuclear Medicine
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• v.36 no.1
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• pp.19-27
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• 2002

The annual incidence of primary brain tumors is 7-19 cases per 100,000 people. The unique capacity of visualizing biochemical processes allows PET to determine functional metabolic activities of the brain tumors. Like other malignant tumors, F-18 FDG has been used commonly in the imaging of brain tumors. FDG PET is valuable in grading malignancy, predicting prognosis, monitoring treatment, differentiating tumor recurrence from radiation necrosis, and detecting primary lesion in metastatric brain tumors. Among amino acids labeled with positron emitters, C-11 methionine is used clinically. Tumor delineation is much better with methionine PET than with FDG PET. Low grade gliomas, in particular, are better evaluated with methionine than with FDG. PET opens another dimension in brain tumor imaging. PET imaging has clearly entered the clinical area with a profound impact on patient care in many indications.

• Korean Journal of Radiology
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• v.20 no.6
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• pp.967-975
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• 2019

Objective: To evaluate whether the combination of magnetic resonance spectroscopy (MRS) and ¹¹C-methionine positron emission tomography (¹¹C-MET PET) could increase accurate diagnostic sensitivity for non-enhancing supratentorial gliomas. Materials and Methods: Between February 2012 and December 2017, 109 patients with non-enhanced supratentorial lesions on contrast-enhanced MRI were enrolled. Each patient underwent MRS and ¹¹C-MET PET before treatment. A lesion was considered to be a glioma when either the MRS or ¹¹C-MET PET results reached the diagnostic threshold. The radiological diagnosis was compared with the pathological diagnosis or medical diagnostic criteria. Results: The sensitivity and specificity were 60.0% and 50.0% for MRS and 75.8% and 50.0% for ¹¹C-MET PET, respectively. Upon combining the two modalities, the sensitivity and specificity of the imaging-based diagnosis prior to surgery reached 89.5% and 42.9%, respectively. Statistically significant differences in the sensitivities were observed between the combined and individual approaches (MRS alone, 89.5% vs. 60.0%, p < 0.001; ¹¹C-MET PET alone, 89.5% vs. 75.8%, p = 0.001). However, no significant differences in specificity were observed between the combined and individual modalities. Conclusion: The combination of MRS and ¹¹C-MET PET findings significantly increases accurate diagnostic sensitivity for non-enhancing supratentorial gliomas without significantly lowering the specificity. This finding suggests the potential of the combined MRS and ¹¹C-MET PET approach in clinical applications.

• Journal of Microbiology and Biotechnology
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• v.18 no.1
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• pp.59-62
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• 2008

The peptide methionine sulfoxide reductases (Msrs) are enzymes that catalyze the reduction of methionine sulfoxide back to methionine. Because of two enantiomers of methionine sulfoxide (S and R forms), this reduction reaction is carried out by two structurally unrelated classes of enzymes, MsrA (E.C. 1.8.4.11) and MsrB (E.C. 1.8.4.12). Whereas MsrA has been well characterized structurally and functionally, little information on MsrB is available. The recombinant MsrB from Bacillus subtilis has been purified and crystallized by the hanging-drop vapor-diffusion method, and the functional and structural features of MsrB have been elucidated. The crystals belong to the trigonal space group P3, with unit-cell parameters a=b=136.096, $c=61.918{\AA}$, and diffracted to $2.5{\AA}$ resolution using a synchrotron-radiation source at Pohang Light Source. The asymmetric unit contains six subunits of MsrB with a crystal volume per protein mass $(V_M)\;of\;3.37{\AA}^3\;Da^{-1}$ and a solvent content of 63.5%.

• Brain Tumor Research and Treatment
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• v.6 no.2
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• pp.47-53
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• 2018

Brain tumors represent a diverse spectrum of histology, biology, prognosis, and treatment options. Although MRI remains the gold standard for morphological tumor characterization, positron emission tomography (PET) can play a critical role in evaluating disease status. This article focuses on the use of PET with radiolabeled glucose and amino acid analogs to aid in the diagnosis of tumors and differentiate between recurrent tumors and radiation necrosis. The most widely used tracer is $^{18}F$-fluorodeoxyglucose (FDG). Although the intensity of FDG uptake is clearly associated with tumor grade, the exact role of FDG PET imaging remains debatable. Additionally, high uptake of FDG in normal grey matter limits its use in some low-grade tumors that may not be visualized. Because of their potential to overcome the limitation of FDG PET of brain tumors, $^{11}C$-methionine and $^{18}F$-3,4-dihydroxyphenylalanine (FDOPA) have been proposed. Low accumulation of amino acid tracers in normal brains allows the detection of low-grade gliomas and facilitates more precise tumor delineation. These amino acid tracers have higher sensitivity and specificity for detecting brain tumors and differentiating recurrent tumors from post-therapeutic changes. FDG and amino acid tracers may be complementary, and both may be required for assessment of an individual patient. Additional tracers for brain tumor imaging are currently under development. Combinations of different tracers might provide more in-depth information about tumor characteristics, and current limitations may thus be overcome in the near future. PET with various tracers including FDG, $^{11}C$-methionine, and FDOPA has improved the management of patients with brain tumors. To evaluate the exact value of PET, however, additional prospective large sample studies are needed.

• Journal of The Korean Society of Inherited Metabolic disease
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• v.13 no.2
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• pp.98-103
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• 2013

Purpose: MAT-I/III deficiency by MAT1A gene mutation causes isolated hypermethioninemia, which is considered to be a clinically benign disease. But in some patients, mental retardation, developmental delay, myelination disorder may be shown. This study was performed to find out the clinical manifestations and genetic characteristics of patients with isolated hypermethioninemia. Methods: Clinical, biochemical and genetic analysis were done to 10 patients with isolated hypermethioninemia who were referred to department of pediatrics, Soonchunhyang University Hospital from March 1999 to March 2012. Results: At first visit, all patients' mean plasma methionine level was 5.5 mg/dL (2.1-14.6) and there were no increase of amino acid levels including homocystine in all patients. Serum homocysteine level was evaluated in seven patients who visited after year 2003, and ranged from 4.96 to $11.15{\mu}mol/L$ (normal < $25{\mu}mol/L$). Methionine restricted diet was started to all patients. Nine patients who managed regularly showed normal development, but one patient whose initial plasma methionine level was 14.6 mg/dL showed language delay at 1 year of age and was diagnosed as mild mental retardation (IQ=66) at 6 years of age. Genetic analysis was done to eight patients, R264H mutation was identified in seven patients. Also, both R299C and R356Q mutation were identified in one patient. Conclusion: Clinical findings in patients with isolated hypermethioninemia were generally good, but one patient showed mental retardation and language difficulty. R264H mutation which usually inherits as an autosomal dominant trait was most frequently found in our patients, and R299C/R356Q mutation were also identified.

• Asian-Australasian Journal of Animal Sciences
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• v.13 no.9
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• pp.1235-1238
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• 2000

Thirty-six Holstein dairy cows were used to evaluate the effect of a rumen protected methionine supplement (RPMet). The cows were divided into two groups of 18 each (control/experimental). The experimental group was given 15 g/d of RPMet (Mepron $^{(R)}$M85, Degussa) from the 4th to the 26th week postpartum. All cows were fed a similar amount of forage including alfalfa silage, corn silage and timothy silage. Concentrate mixture was offered in proportion to the milk yield of each cow. Sufficiency of major metabolizable AAs was checked. Milk yield and milk composition was monitored for each individual cow. A metabolic profile test (MPT) was carried out at the 7th, 11th and 21st week postpartum. Without supplement, both methionine and leucine fell short of the daily requirement. Supplementation with 15 g/d RPMet was calculated to be within a sufficient margin of safety. Milk yield tended to remain higher in the supplemented group than in the controls during supplementation with RPMet. The differences in weekly milk production at the 17th, 18th, 19th and 22nd weeks postpartum were significantly high in the RPMet group (p<0.05). The average 305-d milk yield and the percentages of milk fat, milk protein and solids-not-fat were not affected by the treatment. No differences were observed in either the somatic cell count in the milk or the reproductive status. Judging from MPT, all the cows were in good health during lactation.

• Journal of Korean Neurosurgical Society
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• v.39 no.3
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• pp.176-182
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• 2006

Objective : This study concernes the usefulness of $^{11}C-methyl-L-and$ D-methionine[Met]-positron emission tomography[PET] for glioma grading and detection of recurrence in gliomas, compared with fluorine-18, 2-fluoro-deoxyglucose[FDG]-PET. Methods : Eighty patients underwent Met-PET study for evaluation of glioma : 37 astrocytomas [WHO grade II, 3; III, 8; IV, 26]. 27 oligodendrogliomas [WHO grade II, 16; III, 11]. and 12 suspicious recurrent gliomas. All images were taken within 2 weeks before operation. For suspicious recurrent cases on magnetic resonance images, both FDG-PET and Met-PET were performed. Results : In astrocytoma, Mean maximum standard uptake value[SUV] of region of interest[ROI] was not different between WHO grades [p=0.108]. but ROI/normal contralateral tissue SUV [T/N] ratio was statistically different between WHO grades [p=0.002]. T/N ratio was more closely related to visual scale than maximum SUV of ROI [p<0.001 and p=0.107 respectively]. In oligodendroglioma, there was no statistical difference between WHO grades in view of maximum SUV and T/N ratio. For recurrent gliomas, sensitivity of FDG-PET and Met-PET was 25% and 100%, while specificity of FDG-PET and Met-PET were 100% and 80%, respectively. Conclusion : Met-PET might be an appropriate tool for tumor grading in astrocytoma and be more sensitive for detection of recurrence in gliomas than FDG-PET.