• Title/Summary/Keyword: Medical isotope

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Non-clinical Trials using 14C-Acetaminophen to Validate Biomedical Accelerator Mass Spectrometry System (14C-아세트아미노펜 비임상시험을 통한 생체시료 분석용 가속질량분석기의 검증)

  • Jinho Song;Jae Hoon Shim;Jung Bae Park;Chang Su Yeo;Soo Hyeon Bae;Min Sun Choi;Mi Hye Kwon;Kyeong Min Kim
    • Journal of Radiation Industry
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    • v.17 no.2
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    • pp.127-134
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    • 2023
  • Pharmacokinetic (PK) data provide pivotal information in drug development, and they are usually first studied in the preclinical stage using various animals. However, quite often, animal PK data may not match with human PK, especially in metabolites. Thus, most regulatory agencies in the world make it mandatory to obtain metabolite information using 14C radiolabeled drug in human for small molecule drug candidates. However, such studies are expensive and time consuming and they are usually done at the end of Phase II trials using ~3.7 MBq of 14C labeled drug in a limited number of human subjects. Introduction of accelerator mass spectrometry (AMS) in this kind of study has revolutionized it. Since AMS can measure 14C level as close as natural abundance, it can quantify the amounts of 14C labeled drugs and their metabolites produced in human body that consumes less than the amount of 0.0037 MBq of 14C labeled drug, a very safe level of radioactive dose in human. Therefore, it is now possible to conduct human 14C studies safely in early clinical trials without spending hefty amount of money and time. Korea Radioisotope Center for Pharmaceuticals(KRICP) at Korea Institute of Biological and Medical Sciences(KIRAMS) has established an AMS facility in 2018, housing a 0.5MV AMS manufactured at the US National Electrostatics Corps (NEC). The AMS instrument has been validated using various standard samples that have been prepared at Lawrence Livermore National Laboratory in the US, a worldly reputable provider of AMS standards. In this paper, we present a mass balance study for acetaminophen in rats using AMS and prove that the study results are equivalent with those of literature, which shows the AMS facilities at KRICP has successfully installed and be ready to be used in the various PK studies using 14C labelled compounds for new drug development.

[18F]FET PET is a useful tool for treatment evaluation and prognosis prediction of anti-angiogenic drug in an orthotopic glioblastoma mouse model

  • Kim, Ok-Sun;Park, Jang Woo;Lee, Eun Sang;Yoo, Ran Ji;Kim, Won-Il;Lee, Kyo Chul;Shim, Jae Hoon;Chung, Hye Kyung
    • Laboraroty Animal Research
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    • v.34 no.4
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    • pp.248-256
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    • 2018
  • O-2-$^{18}F$-fluoroethyl-l-tyrosine ($[^{18}F]FET$) has been widely used for glioblastomas (GBM) in clinical practice, although evaluation of its applicability in non-clinical research is still lacking. The objective of this study was to examine the value of $[^{18}F]FET$ for treatment evaluation and prognosis prediction of anti-angiogenic drug in an orthotopic mouse model of GBM. Human U87MG cells were implanted into nude mice and then bevacizumab, a representative anti-angiogenic drug, was administered. We monitored the effect of anti-angiogenic agents using multiple imaging modalities, including bioluminescence imaging (BLI), magnetic resonance imaging (MRI), and positron emission tomography-computed tomography (PET/CT). Among these imaging methods analyzed, only $[^{18}F]FET$ uptake showed a statistically significant decrease in the treatment group compared to the control group (P=0.02 and P=0.03 at 5 and 20 mg/kg, respectively). This indicates that $[^{18}F]FET$ PET is a sensitive method to monitor the response of GBM bearing mice to anti-angiogenic drug. Moreover, $[^{18}F]FET$ uptake was confirmed to be a significant parameter for predicting the prognosis of anti-angiogenic drug (P=0.041 and P=0.007, on Days 7 and 12, respectively, on Pearson's correlation; P=0.048 and P=0.030, on Days 7 and 12, respectively, on Cox regression analysis). However, results of BLI or MRI were not significantly associated with survival time. In conclusion, this study suggests that $[^{18}F]FET$ PET imaging is a pertinent imaging modality for sensitive monitoring and accurate prediction of treatment response to anti-angiogenic agents in an orthotopic model of GBM.

Development of an Isotope Dilution Mass Spectrometry (IDMS)-Based Method for the Analysis of Ibuprofen

  • Lee, Joonhee;Kim, Byungjoo
    • Mass Spectrometry Letters
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    • v.8 no.3
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    • pp.49-52
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    • 2017
  • Ibuprofen is one of the most popular analgesic and antipyretic drugs. An isotope dilution mass spectrometry method based on LC/MS was developed as a candidate reference method for the accurate determination of ibuprofen in pharmaceutical tablets. Isotope labelled ibuprofen, $ibuprofen-d_3$, was added as an internal standard into sample extracts. Ibuprofen and $ibuprofen-d_3$, was analysed by LC/MS in a selected ion monitoring (SIM) mode to detect ions at m/z 205 and 208, respectively. The repeatability and reproducibility of the developed ID-LC/MS method were tested for the validation and assessment of metrological quality of the method.

Simple measurement the chelator number of antibody conjugates by MALDI-TOF MS

  • Shin, Eunbi;Lee, Ji Woong;Lee, Kyo Chul;Shim, Jae Hoon;Cha, Sangwon;Kim, Jung Young
    • Journal of Radiopharmaceuticals and Molecular Probes
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    • v.3 no.2
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    • pp.54-58
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    • 2017
  • Matrix-assisted laser desorption/ionization time-of-flight mass spectrometry(MALDI-TOF MS) is one of the powerful methods that enable analysis of small molecules as well as large molecules up to about 500,000 Da without severe fragmentation. MALDI-TOF MS, thus, has been a very useful an analytical tool for the confirmation of synthetic molecules, probing PTMs, and identifying structures of a given protein. In recent nuclear medicine, MALDI-TOF MS liner ion mode helps researcher calculate the average number of chelator(or linkage) per an antibody conjugate, such as DOTA-(or DFO-) trastuzumab for labeling a medical radioisotope. This simple technique can be utilized to improve the labeling method and control the quality at the development of antibody-based radiopharmaceuticals, which is very effected to diagnosis and therapy for in vivo tumor cells, with radioisotopes like $^{89}Zr$, $^{64}Cu$, and 177Lu. To minimize the error, MALDI-TOF MS measurement is repeatedly performed for each sample in this study, and external calibration is carried out after data collection.

Development of a Nutritional Supplement Certified Reference Material for Elemental Analysis

  • Lee, Jong Wha;Heo, Sung Woo;Kim, Hwijin;Lim, Youngran;Lee, Kyoung-Seok;Yim, Yong-Hyeon
    • Mass Spectrometry Letters
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    • v.9 no.4
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    • pp.105-109
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    • 2018
  • A certified reference material (CRM) for the analysis of inorganic nutrients in nutritional supplements has been developed. Accurate mass fractions of chromium (Cr), iron (Fe), copper (Cu), and zinc (Zn) were determined by isotope dilution inductively coupled plasma mass spectrometry (ID ICP/MS). The measurement results were used to assign certified values for the CRM, which were metrologically traceable to the definitions of the measurement units in the International System of Units (SI). Production of a candidate reference material (RM) and the certification processes are summarized. Each nutrient in the CRM showed good homogeneity, which was estimated using relative standard deviations of the measurement results of twelve bottles in a batch. This CRM is expected to be an important reference to improve reliability and comparability of nutrient analyses in nutritional supplements and related samples in analytical laboratories.

Evaluation of exposure to ionizing radiation of medical staff performing procedures with glucose labeled with radioactive fluorine - 18F-FDG

  • Michal Biegala;Marcin Brodecki;Teresa Jakubowska;Joanna Domienik-Andrzejewska
    • Nuclear Engineering and Technology
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    • v.56 no.1
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    • pp.335-339
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    • 2024
  • Employees of nuclear medicine facilities performing medical procedures with the use of open radioactive sources require continuous detailed control of exposure to ionizing radiation. Thermoluminescent (TL) detectors placed in dosimeters: for the whole body, for lenses, ring and wrist dosimeters were used to assess exposure. The highest whole-body exposure of (1.70 ± 1.09) µSv/GBq was recorded in nurses administering radiopharmaceutical to patients. The highest exposure to lenses and fingers was recorded for employees of the quality control zone and it was (8.08 ± 2.84) µSv/GBq and a maximum of (1261.46 ± 338.93) µSv/GBq, respectively. Workers in the production zone received the highest doses on their hands, i.e. (175.67 ± 13.25) µSv/GBq. The measurements performed showed that the analyzed workers may be classified as exposure category A. Wrist dosimeters are not recommended for use in isotope laboratories due to underestimation of ionizing radiation doses. Appropriately selected shields, which significantly reduce the dose received by employees, must be used in isotope laboratories. Periodic measurements confirmed that the appropriate optimization of exposure reduces the radiation doses received by employees.

The Activity Check of Brachytherapy Isotope (근접치료동위원소의 Activity Check)

  • Kim, Gun-Oh;Lee, Byung-Koo;Kwon, Young-Ho
    • The Journal of Korean Society for Radiation Therapy
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    • v.16 no.1
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    • pp.21-27
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    • 2004
  • An isotope Ir-192, which is used in brachytherapy depends on import in whole quantities. There are a few ways for its activity. measurement using Welltype chamber or the way to rely on authentic decay table of manufacturer. In-air dosimetry using Farmer Chamber, etc. In this paper, let me introduce the way using Farmer chamber which is easier and simple. With the Farmer chamber and source calibration jig, take a measurement the activity of an isotope Ir-192 and compare the value with the value from decay table of manufacturer and check the activity of source. The result of measurement, compared the value from decay table, by ${\pm}2.1\%$. (which belongs to recommendable value for AAPM ${\pm}5\%$ as difference of error range) It is possible to use on clinical medicine. With the increase in use of brachytherapy, the increase of import is essential. And an accurate activity check of source is compulsory. For the activity check of source, it was possible to use Farmer chamber and source calibration jig without additional purchase of Well type chamber.

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