• 한국미생물·생명공학회지
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• 제31권4호
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• pp.377-382
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• 2003

1차 DEAE-Toyopearl 650 M ion exchange column chromatography 및 2차DEAE-Sephadex A-50 ion exchange column chromatography에 의해 정제를 수행한 결과 15.92 units/mg의 정제배율 및 비활성은 92배, 정제 효소의 순도는 SDS-PAGE에 의해 단일 밴드를 나타내었으며, 분자량은 43kDa으로 추정되었다. 래트의 대장암 세포인 RR1022세포와, 사람의 난소암 세포인 SKOV-3 세포에서 RPMI1640 배지와 methionine이 결핍된 RPMI1640 배지를 처리한 결과 정상군에 비해 대조군의 $^{11}$ C-methionine의 섭취 변화가 증가하였다. 종양세포인 RR1022, SKOV-3세포에 methioninase 투여하여 종양세포의 생존율의 변화를 trypan blue 기법으로 확인한 결과 배지내에서 종양세포의 증식에 필요한 methionine의 농도가 감소하여 DNA, RNA, Protein의 합성을 저해한다고 사료된다. 종양세포인 RR1022, SKOV-3세포에 methioninase를 투여한 결과 정상군에 비해 대조군이 시간 지나면서 $^{11}$ C-methionine의 섭취 변화가 증가하였다. 동물의 $^{11}$ C-methionine PET 영상 결과 종양과 염증병변이 모두 관찰되었다. rMET를 투석한 결과 염증병변의 섭취에 비하여 종양의 섭취가 증가하는 경향이 관찰되었으며, 정제한 methioninase를 투여하고 영상을 얻은 경우에도 종양 섭취가 염증보다 높게 나타났다. 종양세포에 methioninase를 처리하면 methionine의 섭취 요구량은 시간이 지나면서 증가하였으며 생존율은 감소하였다. 종양 동물모델에서도 methioninase를 투여한 경우 종양의 좋은 $^{11}$ C-methionine 섭취를 관찰할수 있었으며 methioninase의 이용이 종양의 검출에 유용하게 이용될 수 있을 것으로 사료되었다.

• 핵의학기술
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• 제12권3호
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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.

• 대한방사성의약품학회지
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• 제2권2호
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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.

• 대한핵의학회지
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• 제36권1호
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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.

• Journal of Microbiology and Biotechnology
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• 제18권1호
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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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• 제6권2호
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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.

• 대한유전성대사질환학회지
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• 제13권2호
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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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• 제13권9호
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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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• 제39권3호
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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.

• Bulletin of the Korean Chemical Society
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• 제19권9호
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• pp.952-956
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• 1998

An automated system was developed for the routine preparation of carbon-11 ($^11C$) labeled radiopharmaceuticals, which consisted of three major parts including [$^11C$]methylation of the precursor with [$^11C$] iodomethane ($[^11C]CH_3I)$, purification of the desired product and formulation of the final $^11C$ labeled radiopharmaceutical. The whole system included seven three-way slider valves, eleven solenoid valves, four pneumatic cylinders, a HPLC (High Performance Liquid Chromatography) system and a rotary evaporator. Using this system, we investigated the radiochemical synthesis of L-[$methyl-^11C$]methionine, which is the most widely used amino acid in tumor PET (Positron Emission Tomography) studies. The overall operation took 3035 min including the production of $[^11C]CH_3I$ (10.5 min) and decay-corrected radiochemical yield was 25%. The automated system we described herein can be widely utilized for the preparation of many $^11C$ labeled radiopharinaceuticals and has been shown to be efficient, reliable and easy to operate.