• Journal of radiological science and technology
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• v.30 no.3
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• pp.259-263
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• 2007

For the preparation of $^{99m}Tc$-labeled RBC, $10{\sim}20\;{\mu}g/kg$ of Stannous(II) chloride and $10{\sim}40\;min$ of preparation was used. For finding out the effect of contrast agent, the blood samples were collected in three days, seven days, and 1 months after the diagnostic procedure. In the normal volunteer, the concentration of reducing agent and preparation time did not effect on the radiochemical yield. But in the patients, 10 mg of Stannous(II) chloride and 60 min incubation times was shown high radiochemical yield. Contrast agent has a significant effect on the radiochemical yield. Although the blood samples which were collected after seven days of diagnostic procedure did not effect on the radiochemical yield of $^{99m}Tc$-labeled RBC, but the radiochemical yield of $^{99m}Tc$-labeled RBC which was prepared with a sample of high concentration of contrast agent in blood led to low radiochemical yield. For these samples, the modified method showed high radiochemical yield than previous in vivo preparation method. The recommended method is followed. Blood collecting was performed at 30 minutes after injection of reducing agent, and it is centrifuged for removal of plasma. After addition of $^{99m}TcO^-_4$, sample reservoir was rotated. After addition of normal saline, and it is centrifuged for separation of saline. Then $^{99m}Tc$-labeled RBC was obtained after removal of saline.

• The Korean Journal of Nuclear Medicine
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• v.26 no.1
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• pp.116-123
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• 1992

$^{123}I$ has ideal half life of 13 hours, suitable 159 keV gamma energy for imaging, and easy labeling methods. In Korea Cancer Center Hospital, $^{123}I$ has been produced by MC-50 cyclotron. The purpose of this study is looking for good labeling condition of $^{123}I$ and $^{99m}Tc$ to nonspecific human polyclonal IgG, and comparing these with $^{67}Ga-citrate$ in the abscess bearing mice. Human polyclonal nonspecific IgG was labeled with 0.2 M phosphate buffer added $^{123}I$ by chloramine T method. Human polyclonat nonspecific IgG was labeled with $^{99m}Tc-gluconate$ after activation with $\beta-mercaptoethanol$. In the abscess bearing mice, the radioactivity in the abscess was higher in 24 hours than 6 hours after injection. In the abscess, $^{123}I$ nonspecific IgG had higher uptake than $^{99m}Tc-IgG\;or\;^{67}Ga-citrate$. There was no significant difference in absecess uptake of $^{123}I-IgG$ among 24, 72, 120 hours abscess age. Further clinical researches with $^{123}I-nonspecific$ IgG, and other immunoscintigraphies using $^{123}I$ are expected.

• The Korean Journal of Nuclear Medicine
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• v.32 no.6
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• pp.516-524
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• 1998

Purpose: Radiolabeled CEA79.4 antibody has a possibility to be used in radioimmunoscintigraphy or radioimmunotherapy of cancer. We investigated the in vitro properties and biodistribution of CEA79.4 antibody labeled with Re-188 or Tc-99m. Materials and Methods: CEA79.4 was reduced by 2-mercaptoethanol to produce-SH residue, and was labeled with Re-188 or Tc-99m. For direct labeling of Tc-99m, methylene-diphosphonate was used as transchelating agent. CEA79.4 in 50 mM Acetate Buffered Saline (ABS, pH 5.3) was labeled with Re-188, using stannous tartrate as reducing agent. In order to measure immunoreactivity and the affinity constant of radiolabeled antibody, cell binding assay and Scatchard analysis using human colon cancer cells SNU-C4, were performed. Biodistribution study of labeled CEA79.4 was carried out at 1, 14 and 24 hr in ICR mice. Results: Labeling efficiencies of Tc-99m and Re-188 labeled antibodies were $92.4{\pm}5.9%$ and $84.7{\pm}4.6%$, respectively, In vitro stability of Tc-99m-CEA79.4 in human serum was higher than Re-188-CEA79.4. Immunoreactivity and affinity constant of Tc-99m-CEA79.4 were 59.2% and $6.59{\times}10^9\;M^{-1}$, respectively, while those of Re-188-CEA79.4 were 41.6% and $4.2{\times}10^9\;M^{-1}$, respectively. After 24 hr of administrations of Re-188 and Tc-99m labeled antibody, the remaining antibodies in blood were 6.32 and 9.35% ID/g respectively. The biodistribution of each labeled antibody in other organs was similar because they did not accumulate in non-targeted organs. Conclusion: In vitro properties and biodistribution of Re-188-CEA79.4 were similar to those of Tc-99m-CEA79.4. It appears that Re-188-CEA79.4 can be used as a suitable agent for radioimmunotheraphy.

• The Korean Journal of Nuclear Medicine
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• v.19 no.1
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• pp.137-143
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• 1985

Using chelating agents such as Nitrilotriaceticacid(NTA), ticacid(DTPA) and Ethylenediaminenitrilotetraceticacid(EDTA), with TC-99m were determined in vitro and in vivo. Methods.of separation and determination of TC-99m-liposomes added chelating agents were practiced by thin layer chromatogram scan and gel filtration. Biodistributions of Tc-99m-liposomes in normal and sarcoma 180 cells bearing mice were observed. The results were as follows: 1) Maximum amount of $Sn^{+2}$ to reduction from pertechnetium$(10\sim20{\mu}ci)$ by adding 0, 1, 10 and $100{\mu}g$ of $SnCl_2$ in 0.2 ml of oxygen free water was $10{\mu}g$. 2) The large amounts of $SnCl_2$ were not changed but the small amounts of $SnCl_2$ were much changed by labeling with TC-99m to add chelating agents. EDTA in small amounts of $SnCl_2$ were reduced more strongly than DTPA or NTA. Using a hydrophilic chelate, DTPA, the uptake of liposomes could not accumulated in liver and spleen by a lipophilic chelate NTA were significant in vivo. 3) Uptake by tumor was achived 1.14% of injected dose per gram tissue and tumor to organ ratios were measured in low with TC-99m-NTA-liposomes(+).

• The Korean Journal of Nuclear Medicine
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• v.39 no.3
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• pp.200-208
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• 2005

Purpose: Tc-99m labeled diethylenetriaminepentaacctic acid (DTPA)-coupled galactosylated human serum albumin (GSA) is a currently used imaging agent for asialoglycoprotein receptor (ASGPR) of the liver, but, it has several shortcomings. Recently a new ASGPR imaging agent, $^{99m}Tc$-lactosylated human serum albumin (LSA), with simple labeling procedure, high labeling efficiency, high stability was developed. In order to assess the feasibility of the $^{99m}Tc$-LSA as a ASGPR imaging radiopharmaceuticals, we performed biodistribution study of the tracer in liver injured mice model and the results were compared with histolgic data. Materals and Methods: To induce hepatic damage in ICR mice, diethylnitrosamine (DEN) ($60mg/kg/week{\times}5time$, low dose or $180mg/kg/week{\times}2times$, high dose) and thioacetamide (TAA) ($50mg/kg{\times}1time$) were administrated intraperitoneally. Degree of liver damage was evaluated by tissue hematoxilin-eosin stain, and expression of asialoglycoprotein receptor (ASGPR) was assessed by immunohistochemistry using ASGPR antibody. $^{99m}Tc$-LSA was intravenously administrated via tail vein in DEN or TAA treated mice, and biodistribution study of the tracer was also performed. Results: DEN treated mice showed ballooning of hepatocyte and inflammatory cell infiltration in low dose group and severe hapatocyte necrosis in high dose group, and low dose group showed higher ASGPR staining than control mice in immunohistochemical staining. TAA treated mice showed severe hepatic necrosis. $^{99m}Tc$-LSA Biodistribution study showed that mice with hepatic necrosis induced by high dose DEN or TAA revealed higher blood activity and lower liver activity than control mice, due to slow clearance of the tracer by the liver. The degree of liver uptake was inversely correlated with the degree of histologic liver damage. But low dose DEN treated mice with mild hepatic injury showed normal blood clearance and hepatic activity, partly due to overexpression of ASGPR in mice with mild degree hepatic injury. Conclusion: Liver uptake of $^{99m}Tc$-LSA was inversely correlated with degree of histologic hepatic injury in DEN and TAA treated mice. These results support that $^{99m}Tc$-LSA can be used to evaluate the liver status in liver disease patients.

• 대한핵의학회:학술대회논문집
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• 1976.06a
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• pp.78.2-79
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• 1976

• Toxicological Research
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• v.29 no.1
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• pp.21-25
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• 2013

The selective targeting of an integrin ${\alpha}_v{\beta}_3$ receptor using radioligands may enable the assessment of angiogenesis and integrin ${\alpha}_v{\beta}_3$ receptor status in tumors. The aim of this research was to label a peptidomimetic integrin ${\alpha}_v{\beta}_3$ antagonist (PIA) with $^{99m}Tc(CO)_3$ and to test its receptor targeting properties in nude mice bearing receptor-positive tumors. PIA was reacted with tris-succinimidyl aminotriacetate (TSAT) (20 mM) as a PIA per TSAT. The product, PIA-aminodiacetic acid (ADA), was radiolabeled with $[^{99m}Tc(CO)_3(H_2O)_3]^{+1}$, and purified sequentially on a Sep-Pak C-18 cartridge followed by a Sep-Pak QMA anion exchange cartridge. Using gradient C-18 reverse-phase HPLC, the radiochemical purity of $^{99m}Tc(CO)_3$-ADA-PIA (retention time, 10.5 min) was confirmed to be > 95%. Biodistribution analysis was performed in nude mice (n = 5 per time point) bearing receptor-positive M21 human melanoma xenografts. The mice were administered $^{99m}Tc(CO)_3$-ADA-PIA intravenously. The animals were euthanized at 0.33, 1, and 2 hr after injection for the biodistribution study. A separate group of mice were also co-injected with 200 ${\mu}g$ of PIA and euthanized at 1 hr to quantify tumor uptake. $^{99m}Tc(CO)_3$-ADA-PIA was stable in phosphate buffer for 21 hr, but at 3 and 6 hr, 7.9 and 11.5% of the radioactivity was lost as histidine, respectively. In tumor bearing mice, $^{99m}Tc(CO)_3$-ADA-PIA accumulated rapidly in a receptor-positive tumor with a peak uptake at 20 min, and rapid clearance from blood occurring primarily through the hepatobiliary system. At 20 min, the tumor-to-blood ratio was 1.8. At 1 hr, the tumor uptake was 0.47% injected dose (ID)/g, but decreased to 0.12% ID/g when co-injected with an excess amount of PIA, indicating that accumulation was receptor mediated. These results demonstrate successful $^{99m}TC$ labeling of a peptidomimetic integrin antagonist that accumulated in a tumor via receptor-specific binding. However, tumor uptake was very low because of low blood concentrations that likely resulted from rapid uptake of the agent into the hepatobiliary system. This study suggests that for $^{99m}Tc(CO)_3$-ADA-PIA to be useful as a tumor detection agent, it will be necessary to improve receptor binding affinity and increase the hydrophilicity of the product to minimize rapid hepatobiliary uptake.

• Bulletin of the Korean Chemical Society
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• v.32 no.7
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• pp.2410-2412
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• 2011

Using a single step chemical synthesis, we synthesized the potential tumor imaging agent $^{99m}Tc$-diglucose-diethylenetriamine (DGTA) from diethylenetriamine and natural D-glucose. 10 min Incubation of 10 mg of precursor with 50 ${\mu}g$ of $SnCl_2{\cdot}2H_2O$ at room temperature yielded over 95% of $^{99m}Tc$ labeling. The stability for 6 hours in saline or human plasma was over 90%. In vitro tumor cell uptake assays using the SNU-C5 and 9 L cell lines showed that, in 0-400 mg/dL glucose medium, cell uptake of $^{99m}Tc$-DGTA was 1.5-8 times higher than that of [$^{18}F$]FDG. Moreover, [$^{18}F$]FDG uptake was dependent on glucose concentration in the medium, whereas cellular uptake of $^{99m}Tc$-DGTA was not dependent on glucose concentration, suggesting that the two compounds have different uptake mechanisms by tumor cells.

• The Korean Journal of Nuclear Medicine
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• v.36 no.6
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• pp.333-343
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• 2002

Purpose: A new linker, hydrazino nicotinamide (HYNIC), was recently introduced for labelling of liposome with $^{99m}Tc$. In this study we synthesized HYNIC derivatized PEG (polyethylene glycol)-liposomes radiolabeled with $^{99m}Tc$. Materials and Methods: In order to synthesize HYNIC-DSPE (distearoyl phosphatidyl ethanolamine) which is a crucial component for $^{99m}Tc$ chelation, first of all succinimidyl 6-BOC-hydrazinopyridine-3-carboxylic acid was synthesized from 6-chloronicotinic acid by three sequential reactions. A DSPE derivative of succinimidyl 6-BOC-hydrazinopyridine-3-carboxylic acid was transformed into HYNIC-DSPE by HCI/dioxane. HYNIC-PEG-liposomes were prepared by hydration of the dried lipid mixture of EPC (egg phosphatidyl choline): PEG-DSPE : HYNIC-DSPE:cholesterol (1.85:0.15:0.07:1, molar ratio). The HYNIC-PEG-liposomes were labeled with $^{99m}Tc$ in the presence of $SnCl_2{\cdot}2H_2O$ (a reducing agent) and tricine (a coligand). To investigate the level of in vivo transchelation of $^{99m}Tc$ in the liposomes, the $^{99m}Tc$-HYNiC-PES-liposomes were incubated with a molar excess of DTPA, cysteine or glutathione solutions at $37^{\circ}C$ for 1 hour. The radiolabeled liposomes were also incubated in the presence of human serum at $37^{\circ}C$ for 24 hours. Results: 6-BOC-hydrazinopyridine-3-carboxylic acid was synthesized with 77.3% overall yield. The HYNIC concentration in the PEG-coated liposome dispersion was 1.08 mM. In condition of considering the measured liposomal size of 106 nm, the phospholipid concentration of $77.5\;{\mu}mol/m{\ell}$ and the liposomal particle number of $5.2{\times}10^{14}$ liposomes/ml, it is corresponded to approximate 1,250 nicotinyl hydrazine group per liposome in HYNIC-PEG-liposome. The removal of free $^{99m}Tc$ was not necessary because the labeling efficiency were above 99%. The radiolabeled liposomes maintained 98%, 96% and 99%, respectively, of radioactivity after incubation with transchelators. The radiolabeled liposomes possessed above 90% of the radioactivity in serum. Conclusion: These results suggest that the HYNIC can be synthesized easily and applied in labelling of PEG-liposomes with $^{99m}Tc$.

• Bulletin of the Korean Chemical Society
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• v.30 no.5
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• pp.1107-1112
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• 2009

The aim of this study is to develop and synthesize $5-HT_{1A}$ receptor imaging agents with WAY-100635 moiety and $^{99m}Tc(CO)_3$ core. WAY-100635 is commonly known as $5-HT_{1A}$ antagonist and its labeled compound ([$^{11}C$] WAY-100635) has been used as effective radioligand for imaging brain $5-HT_{1A}$ receptors with PET(Positron Emission Tomography). However, there are several restrictions in using a radioisotope of C-11 and requires for more effective radioisotopes and ligands. In order to produce a structure most similar to WAY-100635, WAY-100635 derivatives containing a cysteine chelator were designed and confirmed by using in silico (Hyperchem). The novel compounds (7a, 7b, 7c) were prepared in five or 7 steps with yields of 16%, 36% and 42%, respectively and radiolabeled with $[^{99m}Tc(CO)_3(H_2O)_3]^{+}$. The labeling yield was 99% for all the newly synthesized compounds. [$^{99m}Tc(CO)_3$]- WAY-100635 derivatives show a neutral charge which were confirmed by paper electrophoresis.