• The Korean Journal of Nuclear Medicine
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• v.33 no.4
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• pp.430-438
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• 1999

Purpose: We evaluated a rapid preparation procedures for the labeling and quality control of $^{99m}Tc$-ECD, $MAG_3$, and MIBI using microwave heating and Sep-Pak cartridges. Materials and Methods: $^{99m}Tc$ labeling of ECD, $MAG_3$, and MIBI kit preparation was performed according to the package inserts with microwave heating modification. Heating time was 10-15 sec, and heating was performed with 3 mm plastic bottle with screw cap to prevent radiation contamination. Labeling efficiency was obtained with $C_{18}$ or Alumina N Sep-Pak cartridges. Results: The radiochemical purity of $93{\sim}96%$ for $^{99m}Tc$-ECD and $95{\sim}99%$ for $^{99m}Tc$-MIBI was obtained using Alumina N Sep-Pak cartridge. The optimum irradiation time of microwave method for 3 ml $^{99m}Tc$-labeled radiopharmaceutical solution was 10 sec for $^{99m}Tc$-ECD and $^{99m}Tc$-MIBI, and 15 sec for $^{99m}Tc-MAG_3$. The results of quality control data with Sep-Pak cartridges were well correlated with TLC method. The total preparation time of these radiopharmcaeuticals was $5{\sim}6min$ including quality control procedure. Conclusion: This study demonstrates that radiopharmaceuticals preparation by microwave heating and quality control by Sep-Pak cartridges can be efficiently utilized as an alternative to the recommended method by manufacturer's manual.

• The Korean Journal of Nuclear Medicine
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• v.30 no.4
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• pp.541-547
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• 1996

The previous monoclonal antibody labeling method for bone marrow immunoscintigrapy was complicated and laborious for clinical application. Also it showed a relatively low labeling efficiency. To improve this procedure, we compared several direct labeling methods of $^{99m}Tc$. 1) The labeling efficiency in the method using gluconate as a transchelator was low (40-70%), but immunoscintigraphy using this radiotracer produced a clear image. 2) To improve labeling efficiency, ${\beta}$-mercaptoethanol was removed after reduction. The labeling efficiency was improved up to 70-80%, but the radioactivity of the blood pool was high. 3) The higest labeling efficiency (>90%) and best quality images could be obtained by using MDP as a transchelating agent. It did not require additional procedures for separation of labeled antibodies. The immunoreactivity of this antibody was 60%. Residual MDP which can be taken up by the bone could be removed by PD-10 column. The reduced antibodies were stable with a high labeling efficiency (>90%) for up to 47 days by deep freezing. We concluded that the improved procedure for $^{99m}Tc$ labeling of anti-NCA-95 monoclonal antibody using MDP as a transchelating agent will be a simple and useful method for clinical application.

• The Korean Journal of Nuclear Medicine
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• v.30 no.3
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• pp.367-371
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• 1996

The $MAG_3$ is a tubular excreting radiopharmaceutical for renal image. We synthesized benzoyl $MAG_3\;(Bz-MAG_3)$ and made a kit for labeling with $^{99m}Tc$. We checked the labeling efficieny of $^{99m}Tc$ labeled $MAG_3$ and biodistribution. Labeling efficieny was checked by TLC-SG (acetonitrile/$H_2O$=2/1). After injecting of 1 mCi of $^{99m}Tc-MAG_3$ to ICR-mice, $T_{max}(min),\;T_{1/2}(min)$ were obtained in the renogram. Sequential images (30sec, 2min, 5min, 10min, 15min, 20min) of $^{99m}Tc-MAG_3$ were compared with those of commercial $^{99m}Tc$-DTPA (Du Pont Merck Pharmaceutical Co.) kit. 1) The $R_f$ value of synthesized $^{99m}Tc-MAG_3$ was 0.78 and labeling efficiency was $97.5{\pm}1.9%$ (n=10). 2) The dynamic images of the $^{99m}Tc-MAG_3$ were better than those of the $^{99m}Tc$-DTPA. 3) The $T_{max}(min.)$ and $T_{1/2}(min.)$ of $^{99m}Tc-MAG_3$ (n=10) were $1.5{\pm}0.5$ (left), $1.4{\pm}0.4$ (right), and $4.3{\pm}1.4$ (left), $4.8{\pm}2.0$ (right), respectively. The $T_{max}(min.)$ and $T_{1/2}(min.)$ of $^{99m}Tc$-DTPA (n=7) were $2.7{\pm}1.6$ (left), $2.7{\pm}1.6$ (right), and $3.8{\pm}1.7$ (left), $4.5{\pm}2.7$ (right), respectively. The quaility of image and labeling efficiency of the synthesized $Bz-MAG_3$ kit were excellent, that it was supposed to be used in routine clinical work.

• The Korean Journal of Nuclear Medicine
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• v.33 no.1
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• pp.84-93
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• 1999

Purpose: We investigated the direct labeling method of antibody with $^{99m}Tc$ and $^{188}Re$ and examined the stability and function of these labeled compounds in in vitro and in vivo. Materials and Methods: Disulfide bond of nonspecific human IgG was reduced to -SH group by 2-mercaptoethanol. Stannous ion was used to reduce $^{99m}Tc$ and $^{188}Re$. The stability of $^{99m}Tc$-IgG and $^{188}Re$-IgG was estimated upto 24 hrs. Biodistribution was evaluated in abscess bearing rats at 4 and 24 hr post-injection of $^{99m}Tc$ or $^{188}Re$ labeled IgG. Results: The number of -SH group per reduced IgG molecule was 2.34. The labeling yield of $^{99m}Tc$-IgG and $^{188}Re$-IgG were 90% and 95%, respectively The stability of $^{99m}Tc$-IgG at 1, 4, 6 and 24 hr was 91%, 83%, 78%, 7% and that of $^{188}Re$-IgG at 1, 4, 16 and 24 hr was 94%, 80%, 47%, 42%, respectively. At 4 hr post-injection of $^{99m}Tc$-IgG, high uptake was found on kidney, blood, stomach and abscess ($9.42{\pm}0.68,\;1.43{\pm}0.24,\;0.86{\pm}0.18,\;0.72{\pm}0.10$ %ID/g, respectively). The uptakes at 24 hr were kidney, abscess,.itomach, and blood in descending order. In case of $^{188}Re$-lgG, high uptake at 4 hr post injection appeared on kidney, blood, abscess and stomach ($3.92{\pm}0.62,\;1.32{\pm}0.08,\;0.88{\pm}0.01,\;0.26{\pm}0.06$, respectively). The uptakes at 24 hr were kidney, abscess, blood and stomach in descending order. The abscess to blood uptake ratio of $^{99m}Tc$-IgG was 0.5 at 4 hr and 2.02 at 24 hr and that of $^{188}Re$-IgG was 0.67 and 1.29. Conclusion: $^{99m}Tc$-IgG and $^{188}Re$-IgG canbe labeled efficiently with direct labeling method. However, $^{99m}Tc$-IgG and $^{188}Re$-IgG, labeled with direct method, was unstable. Further study is needed to enhance the stability of the antibody labeling.

• 대한핵의학회:학술대회논문집
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• 1999.05a
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• pp.193-195
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• 1999

There is considerable interest in $^{188}Re$ due to its favorable properties as a therapeutic radionuclide $^{188}Re$ and $^{99m}Tc$ act as a matched pair because of their similar chemical properties, and therefore methods of labeling with $^{99m}Tc$ can be applied to the labeling with $^{188}Re$. With appropriately chosen agents as carriers of $^{188}Re$, the labeling can be readily carried out using $^{188}ReO_4^-$ in the presence of a reducing agent. $^{188}Re$ radio-pharmaceuticals based on $^{99m}Tc$ complexes have been synthesized and are currently being studied for clinical use. Some of them are shown to be suitable for therapeutic use and promising for radiotherapy in nuclear medicine.

• The Korean Journal of Nuclear Medicine
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• v.39 no.5
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• pp.278-283
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• 2005

Purpose: In prior study, we synthesized $^{99m}Tc$-galactosylated chitosan (GC) and performed in vivo biodistribution study, showed specific targeting to hepatocyte. The aim of this study is to evaluate the labeling efficiency and cytotoxicity of modified galactosylated chitosan compounds, galactosyl methylated chitosan (GMC) and HYNIC-galactosylated chitosan (GCH). Materials and Methods: GC, GMC and GCH were synthesized and radiolabeled with $^{99m}Tc$. Then, they were incubated for 6 hours at room temperature and human serum at $37^{\circ}C$. Labeling efficiencies were determined at 15, 30 m, 1, 2, 3 and 6 h after radiolabeling. To evaluate cytotoxicity, MTT assay was performed in HeLa and HepG2 cells. Results: In comparison with them of $^{99m}Tc$-GC labeling efficiencies of $^{99m}Tc$-GMC were significantly improved (100, 97 and 89%) in acetone and 96.3, 95.8 and 75.6% in saline at 15 m, 1 and 6 h, respectively). Moreover, $^{99m}Tc$-GCH showed more improved labeling efficiencies (>95% in acetone and human serum and >90% in saline at 6 h). In MTT assay, cytotoxicity was very low and not different from that of controls. Conclusion: These results represent that these compounds are radiochemically compatible radiopharmaceuticals, can be used in hepatocyte specific imaging study and in vivo gene or drug delivery monitoring.

• The Korean Journal of Nuclear Medicine
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• v.26 no.2
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• pp.380-391
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• 1992

This study was designed to evaluate a direct method of $^{99m}Tc$ labeling using $\beta-mercaptoethanol$ as a reducing agent, and to investigate whether $^{99m}Tc$ labeled specific monoclonal antibody against carcinoembryonic antigen (CEA-92) can be used for the scintigraphic localization of human colon cancer xenograft. Purified CEA-92 IgG was fragmented into F $(ab')_2$ and then labeled with $^{99m}Tc$ by transchelation method using glucarate as a chelator. Labeling efficiency, immunological reactivity and in vitro stability of $^{99m}Tc$ CEA-92 F $(ab')_2$ were measured and then injected intravenously into nude mice bearing human colon cancer (SNU-C4). Scintigrams were obtained at 24 hour after injection. Then nude mice were sacrificed and the radioactivity was measured Labeling efficiency of injected $^{99m}Tc$ CEA-92 F $(ab')_2$, immunoreative fraction and in vitro stability at 24 hour of injected $^{99m}Tc$ CEA-92 F $(ab')_2$ was 45.2%, 32.8% and 57.4%, respectively. At 24 hour after injection, % ID/g in kidney (46.77) showed high uptake, but %ID/g in tumor (1.65) was significantly higher than spleen (0.69), muscle (0.16), intestine (0.45), stomach (0.75), heart (0.48) and blood (0.45). There was no significant difference between tumor and liver (1.81). Tumor contrast as quantitated by tumor to blood ratio of $^{99m}Tc$ CEA-92 F $(ab')_2$ was increased significantly (p<0.005) until 24 hours (3.70), and there was no statistical differece from tumor to blood ratio of I-131 CEA-92 F $(ab')_2$. The scintigram demonstrated localization of radioactivity over transplanted tumor, but significant background radioactivity was also noted over kidney and abdomen. It is concluded that CEA-92 F $(ab')_2$ can be labeled with $^{99m}Tc$ by a direct transchelation method using $\beta-mercaptoethanol$ as a reducing agent and $^{99m}Tc$ labeled CEA-92 F $(ab')_2$ can be used for the scintigraphic localization of human colon cancer xenograft in nude mice model.

• Toxicological Research
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• v.28 no.4
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• pp.235-240
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• 2012

$^{99m}Tc$ tricarbonyl glycine monomers, trimers, and pentamers were synthesized and evaluated for their radiolabeling and in vivo distribution characteristics. We synthesized a $^{99m}Tc$-tricarbonyl precursor with a low oxidation state (I). $^{99m}Tc(CO)_3(H_2O)_3^+$ was then made to react with monomeric and oligomeric glycine for the development of bifunctional chelating sequences for biomolecules. Labeling yields of $^{99m}Tc$-tricarbonyl glycine monomers and oligomers were checked by high-performance liquid chromatography. The labeling yields of $^{99m}Tc$-tricarbonyl glycine and glycine oligomers were more than 95%. We evaluated the characteristics of $^{99m}Tc$-tricarbonyl glycine oligomers by carrying out a lipophilicity test and an imaging study. The octanol-water partition coefficient of $^{99m}Tc$ tricarbonyl glycine oligomers indicated hydrophilic properties. Single-photon emission computed tomography imaging of $^{99m}Tc$-tricarbonyl glycine oligomers showed rapid renal excretion through the kidneys with a low uptake in the liver, especially of $^{99m}Tc$ tricarbonyl triglycine. Furthermore, we verified that the addition of triglycine to prototype biomolecules (AGRGDS and RRPYIL) results in the improvement of radiolabeling yield. From these results, we conclude that triglycine has good characteristics for use as a bifunctional chelating sequence for a $^{99m}Tc$-tricarbonyl-based biomolecular imaging probe.

• Korean Journal of Veterinary Research
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• v.44 no.1
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• pp.15-21
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• 2004

This paper describes the development of $^{99m}Tc$ tricarbonyl cysteine as potential renal function diagnostic radiopharmaceutical and evaluation of its biological characteristics using experimental animals. l-Cysteine was labeled efficiently with $^{99m}Tc$ tricarbonyl precursor $([^{99m}Tc(CO)_3(H_2O)_3)]^{+})$ under 30 min heating at ${75^{\circ}C}$. Labeling yield and stability were analyzed by high performance liquid chromatography (HPLC). The biodistribution property of $^{99m}Tc$ tricarbonyl cysteine in mice and its dynamic imaging profiles in rabbits were carried out. To investigate the excretion mechanism of $^{99m}Tc$ tricarbonyl cysteine, tubular transport inhibition test with probenecid was adopted. $^{99m}Tc$ tricarbonyl cysteine was obtained with a high labeling yield under the moderate condition. The results of biodistribution experiments of $^{99m}Tc$ tricarbonyl cysteine in ICR mice at 3 and 90 min provided that $^{99m}Tc$ tricarbonyl cysteine was very highly accumulated in the kidney and bladder, thereby almost 99% of $^{99m}Tc$ tricarbonyl cysteine was excreted within 90 min post injection. The same results were confirmed by the whole body dynamic images for 30 minutes and static images in rabbits at given time intervals after injection. Renogram of $^{99m}Tc$ tricarbonyl cysteine in rabbits showed that its $T_{max}$ and $T_{1/2}$ of $^{99m}Tc$ tricarbonyl cysteine were $2.33{\pm}0.56$ and $4.30{\pm}0.79$ min, respectively. The $T_{max}$ of $^{99m}Tc$ tricarbonyl cysteine with probenecid pretreatment was $2.30{\pm}0.17$ min, whereas $T_{1/2}$ of that with probenecid pretreatment was $17.0{\pm}32.47$ min. $T_{1/2}$ of $^{99m}Tc$ tricarbonyl cysteine with probenecid pretreatment was significantly different, as compared to the result without probenecid (p<0.0001). The results showed that the excretion of $^{99m}Tc$ tricarbonyl cysteine was extremely affected by probenecid. Therefore, $^{99m}Tc$ tricarbonyl cysteine was rapidly excreted from the kidney principally by the tubular secretion.

• Nuclear Medicine and Molecular Imaging
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• v.40 no.3
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• pp.177-185
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• 2006

Purpose: Purpose of this study is to synthesize $^{99m}Tc$-labeled transferrin for injection imaging and to compare it with $^{67}Ga$-titrate for the detection of infectious foci. Materials and methods: Succinimidyl 6-hydrazino-nicotinate hydrochloride-chitosan-transferrin (Transferrin) was synthesized and radiolabeled with $^{99m}Tc$. Labeling efficiencies of $^{99m}Tc$-Transferrin were determined at 10 min, 30 min, 1 hr, 2 hr, 4 hr and 8 hr. Biodistribution and imaging studies with $^{99m}Tc$-Transferrin and $^{67}Ga$-citrate were performed in a rat abscess model induced with approximately $2{\times}10^8$ colony forming unit of Staphylococcus aureus ATCC 25923. Results: Successful synthesis of Transferrin was confirmed by mass spectrometry. Labeling efficiency of $^{99m}Tc$-Transferrin was $96.2{\pm}0.7%,\;96.4{\pm}0.5%,\;96.6{\pm}1.0%,\;96.9{\pm}0.5%,\;97.0{\pm}0.7%\;and\;95.5{\pm}0.7%$ at 10 min, 30 min, 1 hr, 2 hr, 4 hr and 8 hr, respectively. The injected dose per tissue gram of $^{99m}Tc$-Transferrin was $0.18{\pm}0.01\;and\;0.18{\pm}0.01$ in the lesion and $0.05{\pm}0.01\;and\;0.04{\pm}0.01$ in the normal muscle, and lesion-to-normal muscle uptake ratio was $3.7{\pm}0.6\;and\;4.7{\pm}0.4$ at 30 min and 3 hr, respectively. On image, lesion-to-background ratio of $^{99m}Tc$-Transferrin was $2.18{\pm}0.03,\;2.56{\pm}0.11,\;3.08{\pm}0.18,\;3.77{\pm}0.17,\;4.70{\pm}0.45\;and\;5.59{\pm}0.40$ at 10 min, 30 min, 1 hr, 2 hr, 4 hr and 10 hr and those of $^{67}Ga$-citrate was $3.06{\pm}0.84,\;4.12{\pm}0.54\;and\;4.55{\pm}0.74 $ at 2 hr, 24 hr and 48 hr, respectively. Conclusion: Transferrin is successfully labeled with $^{99m}Tc$, and its labeling efficiency was higher than 95% and stable for 8 hours. $^{99m}Tc$-Transferrin scintigraphy showed higher image quality in shorter time compared to $^{67}Ga$-citrate image. $^{99m}Tc$-transferrin is supposed to be useful in the detection of the infectious foci.