• The Korean Journal of Nuclear Medicine
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• v.27 no.2
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• pp.277-284
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• 1993

$^{99m}Tc$-MAG3는 세뇨관 배설을 하는 신장 기능 영상용 방사성의 약품으로서, 가운데 $^{99m}Tc$이 있고 1개의 유황과 3개의 질소가 아래쪽 면에 정사각형으로 배치되고 정점에 산소가 위치한 4각 피라미드형을 하고 있다. 그러나 시판되는 신장 영상용 MAG3는 반응성이 강한 -SH기에 의한 부산물 생성을 방지하기 위해 benzoyl기로 보호되어 있으므로 보통 조건으로는 잘 표지되지 않고 10분 정도 끓여주어야 한다. 본 실험에서는 실온에서도 benzoyl기를 잘 끊어지게 하는 이미다졸, 아고마틴, 괴리딘등과 같은 염기성 촉매제를 가하고 여러가지 PH에서 실온에서 반응시켜 본 결과, benzoyl기가 끊어지면서 $^{99m}Tc$과 -SH기가 반응하는 첫번째 반응이 일어난 후에도 산성에서 약알칼리성 범위에서는 중간체가 상당량 생성되고 알칼리성 (pH 10.5)이 되어야 최종 산물로 재빨리 넘어가는 것을 발견하였다. 또한 glucarate, medronate, phthalate, acetate 등 여러가지 다른 transchelating agent를 사용하여 같은 반응을 시킨 후에도 생성된 중간체의 HPLC 피크가 같은 retention time (Rt)을 보이는 것으로 보아 이 중간체의 화학구조내에는 transchelating agent를 포함하지 않는 것으로 보인다. 최종 생성물과 중간체의 ImM 시트테인 용액 중에서의 안정도 시험을 하여 본 결과 최종 생성물은 매우 안정하나 중간체는 불안정한 것을 발견하였다.

• The Korean Journal of Nuclear Medicine
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• v.29 no.3
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• pp.328-331
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• 1995

$^{99m}Tc$ labeled PnAO(propylene amine oxime) derivatives have been widely studied as brain perfusion agents. We synthesized and characterized a PnAO derivative, (RR/SS/ meso)-4,8-diaza-3,9-dimethylundecane-2, 10-dione bisoxime(PRODD). Proton-NMR spectroscopy and thin layer chromatography(silica gel) were performed for its characterization. PRODD was labeled with $^{99m}Tc$ using stannous chloride as reducing agent. The labeling efficiency was determined to be about 85%. Brain uptakes of $4.16{\pm}0.42$ %ID/g and $3.24{\pm}0.13$ %ID/g were found after 10min and 30min after intravenous injection. Brain-to-blood ratios were 1.17 and 0.75 at 10 and 30 minutes, which were lower than 1.3 and 1.9 of the ratios with commercial ${\pm}$-HMPAO. Autoradiographs of rat brain sections showed the gray matter to white matter ratios of $1.13{\pm}0.10$ at 30 min after intravenous injection, which was lower than $1.94{\pm}0.19$ of commercial $^{99m}Tc$-HMPAO. With the above findings, we concluded that the lipophilic $^{99m}Tc$-PRODD complex was able to cross the blood-brain barrier, however the complex showed lower uptake than $^{99m}Tc$-HMPAO in mouse or rat brains. We could suggest possibility that PRODD could be used as another $^{99m}Tc$ chelator.

• The Korean Journal of Nuclear Medicine
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• v.29 no.1
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• pp.98-104
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• 1995

Recently murine monoclonal antibodies have been studied actively for radioimmuno-scintigraphy and radioimmunotherapy, especially on patients with leukemia and lymphoma. In this research, we studied radiolabeling and immunologic characteristics of two in-house anti-leukemic monoclonal antibodies(anti-CALLA & anti-JL-1 antibodies) to make the basis for their clinical application. Each antibody was radiolabeled successfully with $^{99m}Tc$ by pretargeting transchelation method and with $^{125}I$ by lodogen method. We also studied cell binding assay, Scatchard analysis and modulation phenomenon. $^{125}I$ showed 90% labeling efficiency for each anti-body which was satisfactory, but $^{99m}Tc$ showed labeling efficiency below 70%, for which we need better labeling method. In cell binding assay, the immunoreactivity(IR) was low for $^{99m}Tc$-labeled antibodies. Scatchard analysis showed satisfactory data for both binding affinity. The affinity constant and antibody binding sites per cell are around $10^9M^{-1}$ and $10^4$, respectively. There was no modulation phenomenon in cases of $^{125}I$ or $^{99m}Tc$ labeled antibodies. We expect that two anti-leukemic monoclonal antibodies may be useful in diagnosis and therapy for leukemia and lymphoma patients.

• Proceedings of the Korean Nuclear Society Conference
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• 2001.05a
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• pp.548.2-548
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• 2001

• Asian Pacific Journal of Cancer Prevention
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• v.13 no.9
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• pp.4255-4261
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• 2012

The present study was conducted to evaluate radioimmunoimaging (RII) and in vivo distribution of mixed antibodies $^{99m}Tc$-EGFR-mAb and $^{99m}Tc$-CD44-mAb in nude mice bearing human lung adenocarcinoma xenografts. Single and mixed applications of the two radiolabeled monoclonal antibodies (mAbs) were compared. Direct labeling of $^{99m}Tc$ was applied to radiolabel the EGFR and CD44 mAbs. The properties of the radiolabeled antibodies were then characterized. RII and assessment of the distribution of the antibodies in nude mice bearing lung adenocarcinoma xenografts were achieved by applying separate and combined doses of $^{99m}Tc$-EGFR-mAb and $^{99m}Tc$-CD44-mAb. The labeling rates of $^{99m}Tc$ for EGFR-mAb and CD44-mAb were $91.5%{\pm}3.8%$ and $92.3%{\pm}4.1%$ respectively, with specific activities of 2.8 and $2.9MBq/{\mu}g$, respectively, and radiochemical purities (RCP) of 96.5% and 96.2%. The radioactivity uptake of the combined application of both radiolabeled antibodies was clearly higher than with a single application of either alone. The relative values of target-to-nontarget (T/NT) measured through the regional interest (ROI) technique were $5.59{\pm}0.42$ (mixed antibodies), $2.78{\pm}0.20$ ($^{99m}Tc$-EGFR-mAb), and $2.28{\pm}0.16$ ($^{99m}Tc$-CD44-mAb) in the RII. The body distribution of the radiolabeled antibodies and their imaging results were basically identical. Application of the mixed antibodies with $^{99m}Tc$-EGFR-mAb and $^{99m}Tc$-CD44-mAb can increase the radioactivity uptake of tumor tissue, leading to more ideal target-to-nontarget ratios, and therefore superior results.

• Journal of Radiopharmaceuticals and Molecular Probes
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• v.6 no.1
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• pp.3-9
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• 2020

Tetraiodothyroacetic acid (tetrac) is a derivative of thyroid hormone T₄ and causes anti-angiogenesis by blocking T₄ binding to integrin α_vβ₃. In this study, we synthesized [^99mTc]Tc-Cys-Asp-Gly(CDG)-tetrac and evaluated it in vitro as a tumor angiogenesis imaging ligand. The CDG was conjugated to tetrac as a chelator for technetium-99m labeling. The cold vial containing CDG-tetrac, sodium glucoheptonate, and reducing agent was completed under nitrogen-filled atmospheric glove bag. [^99mTc]Tc-CDG-tetrac was synthesized in quantitative yield by heating the cold vial with [^99mTc]TcO₄^- at 100℃ for 30 min. In vitro serum stability of [^99mTc]Tc-CDG-tetrac was measured by incubating the radioligand in 50% fetal bovine serum at 37℃ and analyzing the incubation mixture by radio-TLC, which showed high stability over 6 h (≥ 98%). Cell binding study was carried out by incubating [^99mTc]Tc-CDG-tetrac with human umbilical vein endothelial (HUVE) cells at 37℃ for 6 h. The cell binding of the radioligand increased from 100% at 0.5 h to 293.7% at 6 h in a time-dependent manner. For blocking study, the cells were incubated with the radioligand in the presence of either tetrac (20 μM) or cRGDyK (20 μM) at 37℃ for 4 h. The results demonstrated that the cell binding of the radioligand was inhibited by tetrac (19.1%) or cRGDyK (35.6%), indicating specific binding of the radioligand to integrin α_vβ₃. Thus, this study suggests that [^99mTc]Tc-CDG-tetrac may be a potential radioligand for tumor angiogenesis imaging.

• The Korean Journal of Nuclear Medicine
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• v.26 no.2
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• pp.346-354
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• 1992

Cancer cells have several tumor-associated antigens on the cell surfaces, and antibodies against these antigens have been developed by many investigators. Radiolabeled antibodies have been used as new methods to diagnose and treat malignant tumors. Especially anti-carcinoembryonic antigen (CEA) is the most popular antibody for these purposes. In this investigation, we tried to label $^{131}I$ and $^{99m}Tc $ to anti-CEA monoclonal antibodies which were developed in the Seoul National University College of Medicine. We found CEA-79 and CEA-92 antibodies had the better immunological characteristics among 8 anti-CEA monoclonal antibodies. And radioiodination of CEA-79 could be performed by chloramine-T method, while radioiodination of CEA-92 by iodogen method. To label these antibodies with $^{99m}Tc $, we used pretargeting transchelation as direct labeling method. At first, $^{99m}Tc $ was bound to glucaric acid, and monoclonal antibody was reduced by $\beta-mercaptoethanol$. When these were incubated together. $^{99m}Tc $ bound to glucarate was switched to monoclonal antibody because of higher affinity. We established conditions of several steps in this method. Anti-CEA monoclonal antibodies labeled with $^{131}I$ and $^{99m}Tc $ are expected to be used valuably in the detection and treatment of malignant tumors.

• The Korean Journal of Nuclear Medicine Technology
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• v.13 no.1
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• pp.25-29
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• 2009

Purpose: Several radioactive agents were used for lymphoscintigraphy in breast cancer. But recently, due to the change of local radiopharmaceutical licensing policy and discontinuation of supplies from manufacturer, we could not use many radiocolloids such as $^{99m}Tc$-Antimony Trisulfide Colloid, $^{99m}Tc$-Tin Colloid, $^{99m}Tc$-Human Serum Albumin. So it is necessary to use the substitution radiopharmaceutical. Therefore, this study aims to evaluate the performance of substitution radiopharmaceutical ($^{99m}Tc$-Phytate) including the existing radiocolloids and to set up of the appropriate protocol in lymphoscintigraphy. Materials and Methods: For each radiocolloids ($^{99m}Tc$-Antimony Trisulfide Colloid (ASC), $^{99m}Tc$-Tin Colloid (TC), $^{99m}Tc$-Human Serum Albumin (HSA), $^{99m}Tc$-Phytate) were performed the particle size by Zeta Sizer (Nano-ZS) and we compared the radiolabeling time, procedure and acquisition time for each of the radiocolloids (total 200 patients). For the last time, we made an analysis of image for each of the radiocolloids with our previous report (SJ Jang et al, Korean Nucl Med Mol imaging Vol.41, No.6, Dec 2007). Results: The particle size of each radiocolloids showed A.S.C (50 nm), T.C (310 nm), H.S.A (10.8 nm), $^{99m}Tc$-Phytate (499 nm). The labeling and acquisition time for each of the radiocolloids showed no substantial difference. But there is difference of the labeling time for the A.S.C. because the ASC procedure need to boiling process. There were no significant differences among those radiocolloids (p>0.005) in the identification rate (IR), false negative rate (FNR), and negative predictive value (NPV). Conclusions: $^{99m}Tc$-labeled radiocolloids showed equivalent results in lymphoscintigraphy. Therefore, in this exam of each radiocolloids could be applied appropriate protocol in lymphoscintigraphy.

• Journal of Radiopharmaceuticals and Molecular Probes
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• v.5 no.1
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• pp.18-25
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• 2019

2-Nitroimidazole derivatives have been reported to accumulate in hypoxic tissue. We prepared a novel $^{99m}Tc-MAG_3$-2-nitroimidazole and evaluated the feasibility for hypoxia imaging agent. $Bz-MAG_3$-2-nitroimidazole was synthesized by direct coupling of $Bz-MAG_3$ and 2-nitroimidazole using dicyclohexylcarbodiimide. $Bz-MAG_3$-2-nitroimidazole was labeled with $^{99m}Tc$ in the presence of tartaric acid and $SnCl_2-2H_2O$ at $100^{\circ}C$ for 30 min. And the reaction mixture was purified by $C_{18}$ Sep-pak cartridge. The labeling efficiency and the radiochemical purity were checked by ITLC-SG/acetonitrile. The tumor was grown in balb/c mice for 8~13 days after the subcutaneous injection of tumor cells, CT-26 (murine colon adenocarcinoma cell). Biodistribution study and tumor autoradiography were performed in the xenografted mice after i.v injection of 74 kBq/0.1 mL and 19 MBq/0.1 mL of $^{99m}Tc-MAG_3$-2-nitroimidazole, respectively. In vivo images of $^{99m}Tc-MAG_3$-2-nitroimidazole in tumor bearing mice were obtained 1.5 hr post injection. The labeling efficiency was $45{\pm}20%$ and the radiochemical purity after purification was over 95%. Paper electrophoresis confirmed negative charge of $^{99m}Tc-MAG_3$-2-nitroimidazole. $^{99m}Tc-MAG_3$-2-nitroimidazole was very stable at room temperature and its protein binding was 53%. The $^{99m}Tc-MAG_3$-2-nitroimidazole exhibited high uptake in the liver, stomach and intestine. In biodistribution study using tumor bearing mice, the uptakes (% ID/g) of the tumor were $0.5{\pm}0.1$, $0.4{\pm}0.0$, $0.2{\pm}0.1$ and $0.1{\pm}0.1$ at 5, 15, 30 min and 4 hrs. Tumor/muscle ratio were $1.4{\pm}0.1$, $2.2{\pm}0.83$, $3.0{\pm}0.9$, and 3.7 (n=2) for 5, 15, 30 min and 4 hrs. The uptake in hypoxic area was found higher than in non-hypoxic area of tumor tissue by autoradiography. In vivo images showed the relatively faint uptake to the hypoxic tumor region. $^{99m}Tc-MAG_3$-2-nitroimidazole was successfully synthesized and found feasible for imaging hypoxia.

• The Korean Journal of Nuclear Medicine
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• v.28 no.2
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• pp.167-171
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• 1994

Ethylcystein dimer (ECD) was synthesized by dimerizatlon of L-thiazolidine-4-carboxylic acid in liquid ammania with sodium metal and successive esterification in ethanolic solution of hydrogen chlorde. The purified product was labeled with $^{99m}Tc$ in the presence of sodium glucarate(pH= 5.6) and stannous chloride. Best result was obtained from the preparation con sisting of 0.1mg ECD, $40{\mu}l$ of 0.4M sodium glucarate (pH=5.6), and $20{\mu}g$ of stannous chloride. The labeling efficiency was 90% with previous condition. The labeled $^{99m}Tc$-ECD was stable at least for 3 hours in PBS(pH=7.4) at room temperature. About 10mCi of $^{99m}Tc$-ECD was injected to normal volunteer, and SPECT image of brain was obtained by triple head camera 10 minutes after inection. The image showed similar distribution of radioactivity in brain with that of HMPAO image.