• Biomolecules & Therapeutics
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• v.5 no.3
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• pp.233-238
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• 1997

The distribution and excretion of radioactivity were examined after intraportal administration of sup 166/Ho-chitosan complex at a dose of 1 mcitg (10 mg chitosan/kg) to rats. Whole body macroautoluminographs showed that the radioactivity after an administration was concentrated in liver and perfused primarily to organs including kidney, spleen, and bone marrow, then to muscle and brain. Similar profiles were observed from 2 hr to 168 hr after the administration. The relative percentage of radioactivity in bone and spinal column increased with time, suggesting that free $^{166}$ Ho, released from chitosan complex deposited in the liver, selectively binds to these tissues. $^{166}$ Ho-chitosan complex administered intraportally was excreted less than 4% through urine (2.7$\pm$0.8%) and feces (0.65 $\pm$ 0.4%) up to seven days. These results demonstrate that the radio-activity of $_{166}$ Ho-chitusan complex when administered intraportally, mainly localizes in liver without affec-ting other tissues and organs. Considering the short half life of $^{166}$ Ho and the localization to the liver, $^{166}$ Ho-chitosan complex might be a useful agent in the treatment of hepatic carcinoma.

• Proceedings of the PSK Conference
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• 2003.10a
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• pp.54-55
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• 2003

Radiation therapy has been used for the cancer treatment externally or internally. The external radiation therapy has been widely used, but for the lack of its selectivity it requires strong radiation dose causing the dermal irritation and radiation effect of the normal tissues or organs. So we investigate non-clinical and clinical studies of “Milican inj.”, in which chitosan is chelated with 166-Holmium, as an anticancer agent for internal radiation therapy. (omitted)

• The Korean Journal of Nuclear Medicine
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• v.30 no.3
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• pp.351-360
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• 1996

Chitosan is a polysaccharide of natural orgin obtained by full or partial deacetylation of chitin, a very abudant natural polymer, which has the properties of biocompatibilities, bioaffinities, and biodegradabilities. The free amino group of chitosan should be participated in forming chelate with holmium (${\beta}$-emitter). $^{166}Ho(NO_3)_3\;5H_2O$ of high radionuclidic purity of upto 99.9% was made by neutron irradiation of naturally occuring $^{166}Ho(NO_3)_3\;5H_2O$, and then reacted with the prepared chitosan solution. The effect of pH, reaction time, the concentration and viscosity of chitosan and the amount of $^{166}Ho$ on forming $^{166}Ho$-chitosan complex ($^{166}Ho$-CHICO) were investigated. $^{166}Ho$-chitosan macroaggregate($^{166}Ho$-CHIMA) was made from $^{166}Ho$-CHICO. Their physical properties such as radionuclidic purity, particle size distribution, stability in vitro and vivo were examined. Their high in vitro and vivo stability makes them attractive agents for internal radiotherapy by local administeration.

• Biomolecules & Therapeutics
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• v.5 no.3
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• pp.278-283
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• 1997

DW-166HC ($^{166}$ Holmium ($^{166}$ Ho)-Chitosan complex) is a new radiopharmaceutic anticancer agent with a broad anti-tumoriginec spectrum, especially against human fepatic cancer. DW-166HC was evaluated for the appearance of micronucleus in polychromatic erythrocytes (PCEs) of mouse bone marrow cells after subcutaneous and intravenous single administration. Bone marrow cells were prepared at 24 hr and 48 hr after DW-166HC-I ($^{165}$ Ho-Chitosan complex cold compound) administration and at 24 hr, 72 hr and 2 weeks after DW-166HC ($^{166}$ Ho-Chitosan complex : hot compound) administration. The results showed there was no statistically significant increase of the numbers of PCEs with micronucleus in all DW-166HC-I administered groups compared with a negative control group but there was statistically significant increase of the numbers of PCEs with micronucleus at 24 hr and 72 hr in all DW-166HC administered groups, which was recovered after 2 weeks from the drug administration. The results also showed the ratio of normochromatic erythrocytes (NCEs) to PCEs of all DW-166HC-I administered groups was not significantly different from that of a negative control group but there was significant difference this ratio at 24hr and 72 hr in all DW-166HC administered groups compared with that of negative group, which was also recovered after two weeks from the drug administration. These results suggested that DW-166HC-I may not cause any chromosomal damage but DW-166HC has in vivo mutagenic potential because of its radioactivity.

• Proceedings of the Korean Society of Applied Pharmacology
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• 1999.04a
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• pp.53-61
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• 1999

Radiation therapy has been used for the cancer treatment and radiation synovectomy$\^$1-3)/. There are two kinds of radiation therapy; the external radiation therapy and the internal radiation therapy. Hitherto, the external radiation therapy has been widely used, but for the lack of its selectivity it requires strong radiation dose and causes the irritation and damage of the normal tissue or organ. Therefore many researchers give their interests to the internal radiation therapy in which the radioactive materials are injected directly into the target organ or tissue. Many ${\beta}$-emitting radionuclides have been studied for the application of the internal radiation theraily. Among them, Holmium-166 has the many beneficial physical characteristics for the internal radiation therapy such as appropriate half life (26.8hr), high ${\beta}$ energy (max. 1.85 MeV(51%), 1.77 MeV (48%), mean 0.67MeV), and low ${\gamma}$ energy (0.081MeV) easily detected by ${\gamma}$-camera. In the internal radiation therapy, the administered radioactive materials should be retained in the target long enough to increase the therapeutic effects and avoid the damage in the normal tissue or organ. For this purpose, radionuclides are used as complex form with carriers. Carriers should have a high affinity with radionuclides in vivo and in vitro, so the complex can be evenly distributed in the lesion but can not be leaked out from the lesion.

• 대한임상약리학회:학술대회논문집
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• 1999.12a
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• pp.48-48
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• 1999

• The Korean Journal of Nuclear Medicine
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• v.34 no.1
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• pp.62-73
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• 2000

Purpose: Esophageal cancer patients have a difficulty in the intake of meals through the blocked esophageal lumen, which is caused by an ingrowth of cancer cells and largely influences on the prognosis. It is reported that esophageal cancer has a very low survival rate due to the lack of nourishment and immunity as the result of this. In this study a new radioactive stent, which prevents tumor ingrowth and restenosis by additional radiation treatment, has been developed. Materials and Methods: Using ${\ulcorner}HANARO{\lrcorner}$ research reactor, the radioactive stent assembly ($^{166}Ho$-SA) was prepared by covering the metallic stent with a radioactive sleeve by means of a post-irradiation and pre-irradiation methods. Results: Scanning electron microscopy and autoradiography exhibited that the distribution of $^{165/166}Ho\;(NO_3)$ compounds in polyurethane matrix was homogeneous. A geometrical model of the esophagus considering its structural properties, was developed for the computer simulation of energy deposition to the esophageal wall. The dose distributions of $^{166}Ho$-stent were calculated by means of the EGS4 code system. The sources are considered to be distributed uniformly on the surface in the form of a cylinder with a diameter of 20 mm and length of 40 mm. As an animal experiment, when radioactive stent developed in this study was inserted into the esophagus of a Mongrel dog, tissue destruction and widening of the esophageal lumen were observed. Conclusion: We have developed a new radioactive stent comprising of a radioactive tubular sleeve covering the metallic stent, which emits homogeneous radiation. If it is inserted into the blocked or narrowed lumen, it can lead to local destruction of the tumor due to irradiation effect with dilatation resulting from self-expansion of the metallic property. Accordingly, it is expected that restenosis esophageal lumen by the continuous ingrowth and infiltration of cancer after insertion of our radioactive stent will be decreased remarkably.