• 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.

• Biomolecules & Therapeutics
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• v.5 no.1
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• pp.100-105
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• 1997

DW-166HC ($^{166}$Holmium-chitosan) is a complex of $^{166}$Ho, $\beta$- and $\gamma$-ray emitter, and chitosan, a polymer of glucosamine, with radiotherapeutic potential. The current study was performed to determine the acute toxicities of $^{165}$Ho-chitosan in mice by two different routes of administration. The both sex mice were given a single intravenous bolus injection of $^{165}$Ho-chitosan complex at doses of 12, 10, 6, 5 and 4 mg/kg or subcutaneous administration at doses of 600, 500, 400 and 300 mg/kg. Chitosan was dosed to control animals as 16 and 800 mg/kg, intravenously and subcutaneously, respectively. The doses of $_{165}$Ho-chitosan complex were expressed as $_{165}$holmium nitrate pentahydrate and the ratio of $^{165}$Ho$(NO_3)_3$).$5H_2O$ to chitosan was 3/4 Severe convulsion and respiratory failure were followed by death within 10 min after intravenous dosing. Transient unilateral hindlimb hypokinesias were found in two mice of 5 mg/kg dosing group during the study period. No abnormalities were observed during the necropsy of survived animals in intravenous dosing group. Only one male animal was found dead in 500 mg/kg subcutaneously dosed group. Alopecia with or without cutaneous ulcer were found in most mice including control animals. During necropsy, omental adhesion was observed in all dose ranges and enlarged spleen was found in several animals including control group. It is suggested that the acute intravenous >).$LD_{50}s$ for male and female mice were 4.90 and 6.03 mg/kg, respectively. The lowest lethal dose in male was 500 mg/kg by subcutaneous administration.

• 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.