• 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.

• Journal of Radiation Industry
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• v.9 no.3
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• pp.111-117
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• 2015

In this paper, production of $^{166}Ho$ by double neutron capture from HANARO research reactor was evaluated. This production approach provides $^{166}Ho$ with high specific activity. $^{164}Dy$ is transmuted into $^{165g+m}Dy$ by (n,${\gamma}$) reaction, then $^{165g+m}Dy$ is transmuted into $^{166}Dy$ by (n,${\gamma}$) reaction. At the end of neutron irradiation, population of $^{166}Dy$ atoms reaches highest point. And $^{164}Dy$ exists as a mixture with $^{165m}Dy$, $^{165}Dy$, $^{166}Ho$ and $^{165}Ho$ at this point. To obtain $^{166}Ho$ with high specific activity, Ho isotopes from irradiated target is separated out. Then $^{166}Ho$ decayed from $^{166}Dy$ is eluted at radioactive equilibrium state. At each step, the number of relevant nuclide is calculated by the state equation. The neutron irradiation time for maximum $^{166}Dy$ is calculated for 283 hour. When 100 mg target of $Dy_2O_3$ (96.8% enriched $^{164}Dy$) is used, possible activity of $^{166}Ho$ is 3.54 Ci($1.31{\times}10^{11}Bq$). For separation efficiency of Dy/Ho is 99.99%, $^{166}Ho/Ho$ is 0.62.

• The Korean Journal of Nuclear Medicine
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• v.31 no.4
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• pp.433-439
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• 1997

$^{166}Ho$-chitosan complex, or $^{166}Ho$-CHICO, is a candidate pharmaceutical for intracavitary radiation therapy of cystic brain tumors because of the desirable nuclear characteristics of $^{166}Ho$ for therapeutic use and the suitable biological and chemical characteristics of chitosan, not to mention its ready producibility The amount of $^{166}Ho$-CHICO to be administered to obtain the goal therapeutic effect can be suggested by predicting the dose to the cyst wall for a varying pharmaceutical dose. When $^{166}Ho$-CHICO is infused into the cyst, the major part of the energy delivery by beta particles emitted from $^{166}Ho$ occurs in the cyst wall within 4mm in depth from the cyst wall surface. Also, realizing the attachment of $^{166}Ho$-CHICO to the cyst wall surface would change the predictions of dose to the cyst wall.

• 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.

• Journal of Korean Neurosurgical Society
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• v.29 no.10
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• pp.1309-1315
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• 2000

Objectives : We performed an in vivo experiment to investigate the effect of $^{166}Holmium$ and $^{166}Holmium$-chitosan complex($^{166}Ho$-CHICO) on the normal brain of rats and to determine the sublethal dose of $^{166}Ho$-CHICO. Materials and Methods : $^{166}Ho$ is a beta and gamma ray emitter. $^{166}Ho$-CHICO is a novel radio-pharmaceutical complex with chitosan to facilitate the transport of $^{166}Ho$ obtained from Korea Atomic Energy Research Center(Taejon, Korea). It is in acidic form and becomes gel state at alkaline pH. One hundred and seventy consecutive rats were divided into four groups : $^{166}Ho$ treated(n＝50), $^{166}Ho$-CHICO treated(n＝57), saline treated(n＝5) and chitosan treated(n＝5) groups. $^{166}Ho$ and $^{166}Ho$-CHICO were injected into the rat brain stereotactically with various doses of 0.1mCi/$20{\mu}l$, 0.2mCi/$20{\mu}l$, 0.3mCi/$20{\mu}l$, and 0.4mCi/$20{\mu}l$ using an automated microinjector. Nuclear imaging, histopathological and hematological studies were performed in 10 rats in each group at 1 day, 3days, 7 days, 1 month and 3 months after the injections. Results : An infiltration of inflammatory cells and necrotic changes were noted in $^{166}Ho$ treated group at 1 week after the injection. A wedge-shaped tissue defect due to necrosis, lined with infiltrated glial cells in $^{166}Ho$ treated group and a cystic defect lined with reactive astroglial cells in $^{166}Holmium$-CHICO treated group at 3 months after the injection were observed. $^{166}Ho$ alone without chitosan leaked out and caused necrotic lesion on the cerebral surface but $^{166}Holmium$-CHICO treated group did not show this feature. As the dose of $^{166}Ho$ increased, the mortality rates were also increased. The mortality rate of the $^{166}Holmium$-CHICO group was higher than the $^{166}Ho$ treated group at a dose of 0.4mCi/$20{\mu}l$/300g. There was no detectable radioactivity due to the leakage or extravasation from the injected site of the brain on the scintigraphy performed at 1 hour, 24 hours and 48 hours after the injection. There was also no detectable activity of $^{166}Holmium$-CHICO in other organs including spleen, liver and kidney. Conclusions : $^{166}Ho$-CHICO did not leak out to the critical cortical surface of the brain from the injection site and induced radiation changes of the parenchyma around the injection site without cortical damage. The sublethal dose of $^{166}Ho$-CHICO for the normal brain in rats was determined to be 0.2mCi/$20{\mu}l$/300g.

• 대한핵의학회:학술대회논문집
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• 1999.05a
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• pp.200-204
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• 1999

Rheumatoid arthritis (RA) is o chronic inflammatory disease of joints with proliferation of synovial epithelial tissue. Therapeutic approach of the RA consists of pharmacological and surgical interventions. Synovectomy is indicated in patients with progressive inflammatory signs and symptoms intractable to medical treatment including local intracavitary steroid injection. Recently, local injection of radionuclides which emit high energy beta rays are labeled with chemical compounds such as $^{90}Y,\;^{165}Dy-ferric$ hydroxide macroaggregate and have been introduced as an alternative therapeutic modality to surgical synovectomy. Holmium-166 is one of beta emitter and Ho-166-chitosan complex was developed for radiation synovectomy. Preclinical trial is on-going at our hospital using Ho-166-chitosan. The procedure and methods of preclinical trial are discussed.

• 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.

• The Korean Journal of Nuclear Medicine
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• v.32 no.1
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• pp.99-108
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• 1998

Intraperitoneal administration of radioisotopes is suggested to treat the metastatic ovarian cancer in the peritoneal cavity. Administering beta-emitting radioisotopes into the peritoneal cavity allows the maximum energy delivery to the cancerous cells of the peritoneal wall surface while sparing the normal cells located in deep site of the peritoneal wall. In this study, dose estimates of the peritoneal wall are provided to be used for prescribing the amount of $^{166}Ho$-chitosan complex administered. The $^{166}Ho$-chitosan complex diffused in the peritoneal fluid may attach to the peritoneal wall surface. The attachment fraction of $^{166}Ho$-chitosan complex to the peritoneal wall surface is obtained by simulating the ascites with Fischer rats. Both volume source in the peritoneal fluid and the surface source over the peritoneal wall surface are counted for the contribution to the peritoneal wall dose. The Monte Carlo code EGS4 is used to simulate the energy transfer of the beta particles emitted from $^{166}Ho$. A plane geometrical model of semi-infinite volume describes the peritoneal cavity and the peritoneal wall. A semi-infinite plane of $10{\mu}m$ in thickness at every 1 mm of depth in the peritoneal wall is taken as the target in dose estimation. Greater than 98 percents of attachment fraction has been observed from the experiments with Fischer rats. Given $1.3{\mu}Ci/cm^2$ and $2.4{\mu}Ci/ml$ of uniform activity density, absorbed dose is 123 Gy, 8.59 Gy, 3.00 Gy, 1.03 Gy, and .327 Gy at 0 mm, 1 mm, 2 mm, 3 mm, and 4 mm in depth to the peritoneal wall, respectively.

• Progress in Medical Physics
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• v.10 no.3
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• pp.151-157
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• 1999

The GafChromic film was used for the dosimetry of a balloon angio catheter filled with the radioisotope HO-166 for endovascular irradiation. The balloon angio catheter was 2 cm long and 3 mm in diameter when inflated. The isotope, Ho-166, was produced by the neutron bombardment using the research reactor in Korea Atomic Energy Research Insititute. Co-60 teletherapy beam was used for making H-D curve for the Gaf-Chromic film. The film dosimetry was measured with a videodensitometer. The radial dose distribution indicated that the absorbed dose dropped to about 20% of the surface dose at the 1 mm away from the balloon surface and at 5 mm position the dose decreased to below 1% of the surface dose. The result also shows that with the specific activity of Ho-l66, 250 mCi/ml it takes 230 seconds to deliver 1200 cGy to the region where is 1mm away from the balloon surface. The concentric isodose curves were also presented. The Ho-166 is an another alternative for endovascualr irradiation to prevent restenosis after PTCA (Percutaneous Trans Coronary Angioplasty)

• Journal of Korean Neurosurgical Society
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• v.54 no.3
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• pp.175-182
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• 2013

Objective : Intracavitary injection of beta-emitting radiation source for control of cystic tumors has been tried with a benefit of localized internal radiation. The authors treated cystic brain tumor patients with Holmium-166-chitosan complex (Ho-166-chico), composed of a beta-emitting radionuclide Holmium-166 and biodegradable chit polymer, and evaluated the safety and effective measurement for response. Methods : Twenty-two patients with recurrent cystic brain tumor and/or located in a deep or eloquent area were enrolled in this pilot study. The cyst volume and wall thickness were determined on CT or MRI to assess radiological response. The activity of Ho-166-chico injected via Ommaya reservoir was prescribed to be 10-25 Gy to the cyst wall in a depth of 4 mm. Results : There was neither complications related to systemic absorption nor leakage of Ho-166-chico in all 22 patients. But, two cases of oculomotor paresis were observed in patients with recurrent craniopharyngioma. Radiological response was seen in 14 of 20 available follow-up images (70%). Seven patients of 'evident' radiological response experienced more than 25% decrease of both cyst volume and wall thickness. Another 7 patients with 'suggestive' response showed decrease of cyst volume without definitive change of the wall thickness or vice versa. All patients with benign tumors or low grade gliomas experienced symptomatic improvement. Conclusion : Ho-166-chico intracavitary radiation therapy for cystic tumor is a safe method of palliation without serious complications. The determination of both minimal effective dosage and time interval of repeated injection through phase 1 trial could improve the results in the future.