• Title/Summary/Keyword: Medical radioisotope

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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.

Similarity of Intracellular Signaling Toward Apoptosis Following UVB and UVC Irradiation

  • Horikawa, Miwa;Matsuda, Naoki;Yoshida, Masahiro;Okumura, Yutaka;Watanabe, Masami;Mori, Toshio
    • Journal of Photoscience
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    • v.9 no.2
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    • pp.482-484
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    • 2002
  • UV irradiation activates various intracellular signaling pathways causing cell death in a DNA damage-dependent and an independent manner. As DNA photoproducts, major forms of DNA damage, are maximally formed by UV light at 260-nm, short wavelength UV (UVC) is more harmful than middle wavelength UV (UVB). However, the differences or similarities in responses of DNA damage-independent intracellular signaling molecules to UVB and UVC are not elucidated. We examined activation of signaling molecules towards apoptosis in normal human fibroblastic cells after irradiation with UVB or UVC at a dose generating the equal amount of DNA photoproducts. Both UVB and UVC induced transient phosphorylation of ERK and sustained phosphorylation of p38. Phosphorylation of p53 at Ser15 and at Ser392 residues were also observed, which were inhibited by a phosphoinositide 3-kinase inhibitor, wortmannin. In contrast, an antioxidant N-acetyl-cysteine and a p38 inhibitor SB203580 suppressed only Ser392 phosphorylation, suggesting that UV-induced oxidative stress and p38 activation were involved in the phosphorylation of this site. The apoptic signals such as mitochondrial cytochrome C release and annexin V binding were then observed. Overall, no difference was found in chronological responses of p53, MAPK, and apoptosis between UVB-irradiated and UVC-irradiated cells. These results suggested that DNA damage-independent intracellular signaling molecules similarly responded to UVB and UVC when the equal level of DNA photoproducts were generated.

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Comparison and evaluation of 89Zr-labeled trastuzumab and Thio-trastuzumab : a potential immuno-PET probe for HER2-positive carcinomas

  • Un Chol Shin;Seoku Bae;Suk-man Kim;Min-Woo Lee;Han Sang Jin;Hyun Park;Kyo Chul Lee;Jung Young Kim;Ji Woong Lee
    • Journal of Radiopharmaceuticals and Molecular Probes
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    • v.7 no.2
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    • pp.105-111
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    • 2021
  • 89Zr is a positron-emitting radioisotope, which has known as well-suited radioisotope for use in a monoclonal antibody-based imaging agent for immuno-PET. The purpose of this study was to quantitatively evaluate the diagnostic ability of general trastuzumab and thio-trastuzumab as HER2 positive receptors based on Df hexadentate iron chelator. Desferrioxamine-p-SCN (Df-Bz-NCS) and desferroixamine-maleimide (Df-Mal) were purchased from Macrocyclics (Dallas, TX, USA). The trastuzumab was purchased from Roche (Schweiz), and thio-trastuzumab was obtained from professor Hyo-Jeong Hong group (Kangwon National University). The radioisotope 89Zr was produced by domestic purification system and KIRAMS using medical cyclotron (50 MeV, Scantronix). The conjugates of Df-trastuzumab and Df-thio-trastuzumab were prepared with Df-Bz-NCS and Df-Mal under basic aqueous solution (pH 8-9) at room temperature, respectively. The conjugates purified by PD-10 column were mixed with dried 89Zr chloride. 89Zr-labeled conjugates were purified and concentrated by Amicon ultra centrifugal filter. The preparation step and time of 89Zr-labeled conjugates was shorted as 4 steps within 2 hours. 89Zr-labeled conjugates showed the highly radiochemical purity of over 98%, and were very stable until 7 days by the analysis of radio-ITLC method. Each radio-labeled conjugates were also exhibited the highly stability in both PBS buffer and mouse serum. Immuno-PET imaging of 89Zr-labeled conjugates in mice bearing gastric cancer xenograft tumors with HER2 expression showed high tumor uptake in the NCI-N87 HER2-expressing. However, 89Zr-Df-Mal-thio-trastuzumab showed a relatively lower tumor-to-background ratio than 89Zr-Df-Bz-trastuzumab, as well as whole-body distribution. In the results, 89Zr-Df-Bz-trastuzumab was evaluated to have a relatively higher HER2 diagnostic ability than 89Zr-Df-Mal-thio-trastuzumab.

Calculation of Effective Half-life of Gamma Emission Radionuclide using Bio-kinetic Model (생체역동학 모델을 이용한 감마선 방출 핵종의 유효반감기 계산)

  • Lee, Sang-Kyung;Jeong, Kyu-Hwan;Lee, Ji-Yon;Kim, Bong-Gi;Kim, Jung-Min
    • Journal of Radiation Industry
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    • v.12 no.4
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    • pp.277-285
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    • 2018
  • Patients administered radioisotope for medical purposes are regulated by each country to quarantine them until their body's radioactivity contents decrease below release criteria. To predict the quarantine period and provide it to medical staffs and patients, it is necessary to approach the assessment of the exposure dose of persons due to patients in a realistic manner. For this purpose, a whole-body effective half-life should be applied to the dose assessment equation instead of the physical half-life. In this study, we constructed a bio-kinetic model for each nuclear species based on the ICRP publication to obtain a whole-body effective half-life of 10 unsealed gamma-ray emitting nuclei from the notification of Nuclear Safety and Security Commission, and calculated the effective half-life mathematically by simulating the distribution of the radioisotope administered in the whole body as well as each organ scale. The whole-body effective half-life of $^{198}Au$, $^{67}Ga$, $^{123}I$, $^{111}In$, $^{186}Re$, $^{99m}Tc$, and $^{201}TI$ were 1,93, 2.57, 0.295, 2.805, 1.561, 0.245, and 2.397 days respectively. However, it was found to be undesirable to offer a single value of the effective half-life of $^{125}I$, $^{131}I$, and $^{169}Yb$ because the changes in the effective half-life show no linearity. A bio-kinetic model created for the internal exposure assessment has been shown to be possible to calculate the effective half-life of radioisotopes administered in the patient's body, but subsequent studies of radiolabeled compounds are required as well.

Image-based Absorbed Dosimetry of Radioisotope (영상기반 방사성동위원소 흡수선량 평가)

  • Park, Yong Sung;Lee, Yong Jin;Kim, Wook;Ji, Young Hoon;Kim, Kum Bae;Kang, Joo Hyun;Lim, Sang Moo;Woo, Sang-Keun
    • Progress in Medical Physics
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    • v.27 no.2
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    • pp.86-92
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    • 2016
  • An absorbed dose calculation method using a digital phantom is implemented in normal organs. This method cannot be employed for calculating the absorbed dose of tumor. In this study, we measure the S-value for calculating the absorbed dose of each organ and tumor. We inject a radioisotope into a torso phantom and perform Monte Carlo simulation based on the CT data. The torso phantom has lung, liver, spinal, cylinder, and tumor simulated using a spherical phantom. The radioactivity of the actual absorbed dose is measured using the injected dose of the radioisotope, which is Cu-64 73.85 MBq, and detected using a glass dosimeter in the torso phantom. To perform the Monte Carlo simulation, the information on each organ and tumor acquired using the PET/CT and CT data provides anatomical information. The anatomical information is offered above mean value and manually segmented for each organ and tumor. The residence time of the radioisotope in each organ and tumor is calculated using the time activity curve of Cu-64 radioactivity. The S-values of each organ and tumor are calculated based on the Monte Carlo simulation data using the spatial coordinate, voxel size, and density information. The absorbed dose is evaluated using that obtained through the Monte Carlo simulation and the S-value and the residence time in each organ and tumor. The absorbed dose in liver, tumor1, and tumor2 is 4.52E-02, 4.61E-02, and 5.98E-02 mGy/MBq, respectively. The difference in the absorbed dose measured using the glass dosimeter and that obtained through the Monte Carlo simulation data is within 12.3%. The result of this study is that the absorbed dose obtained using an image can evaluate each difference region and size of a region of interest.

Calculation of Proton-Induced Reactions on Tellurium Isotopes Below 60 MeV for Medical Radioisotope Production

  • Kim, Doohwan;Jonghwa Chang;Yinlu Han
    • Nuclear Engineering and Technology
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    • v.32 no.4
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    • pp.361-371
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    • 2000
  • The 123Te(p,n)123I, 124Te(p,n)124I and 124Te(p,2n)123I reactions, among the many reaction channels opened, are the major reactions under consideration from a diagnostic purpose because reaction residuals as the gamma emitters are used for most radiophamaceutical applications involving radioiodine. Based on the available experimental data, the absorption cross sections and elastic scattering angular distributions of the proton-induced nuclear reaction on Te isotopes below 60 MeV are calculated using the optical model code APMNK. The transmission coefficients of neutron, proton, deuteron, trition and alpha particles are calculated by CUNF code and are fed into the GNASH code. By adjusting level density parameters and the pair correction values of some reaction channels, as well as the composite nucleus state density constants of the pre-equilibrium model, the production cross sections and energy-angle correlated spectra of the secondary light particles, as well as production cross sections and energy distributions of heavy recoils and gamma rays are calculated by the statistical plus pre-equilibrium model code GNASH. The calculated results are analysed and compared with the experimental data taken from the EXFOR. The optimized global optical model parameters give overall agreement with the experimental data over both the entire energy range and all tellurium isotopes.

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