Taxol 유도체들의 생물학적 거동에 관한 연구

오옥두,유대웅,임상무 ( Ok Doo Awh,Dae Wung Yoo,Sang Moo Im ) 대한핵의학회 1997 핵의학 분자영상 Vol.31 No.4

This study was designed to prospect the 'In-labelled paclitaxel as tumor imaging agent. In order to provide a taxol molecule with a functional group which is able to chelate In-lll, taxol-DTPA conjugate and 2-hemisuccinyltaxol were synthesized by esterification of taxol at C-2 on C-13 carbon with DTPA anhydride and succinic anhydride, respectively. Synthesis yield of the taxol derivatives was 34% for taxol- DTPA and 80% for 2'-hemisuccinyltaxol. Cytotoxicity of the taxol derivatives were measured by MTT method toward cell lines HT29, B16, P388, and CT26. The cytotoxic activities of the taxol derivatives were maintained, although less active than taxol. Radiolabelling of the taxol derivatives were proceeded directly with InCh or indirectly with In-citrate(ligand-exchange method). The ligand-exchane methocl was not suitable because some precipitat:es appeared during the reaction. On the contrary, by direct radiolabelling methnd, we were able to obtain taxol DTPA--'In in 100% radiochemical yield. However, 2'-hemisuccinyltaxol was not labellecl by both methods. Yield and radiochemiral purity of the radiolabelled com- pound were determined by HPI.C, paper chromatography and instant thin layer chromatography. Taxol-DTPA-In was characterized to be hydrophilic by lipophi- licity test, and nearly non-adhesive to HT29, E316, P388, and CT26 by cell hinding affinity test. Binding affinity of the taxol-DTPA-'In complex to serum proteins was also examined by protein precipitation with 30% trichloroacetic acid. The results showed that 309o of the taxol-DTPA-'In complex binds with serum proteins.

123I , 99mTc 사람 비특이 IgG 및 67Ga - Citrate의 실험동물에서 염증병소 섭취율의 비교

오옥두(Ok Doo Awh),임상무(Sang Moo Lim),이종두(Jong Doo Lee),우광선(Kwang Sun Woo),정위섭(Wee Sup Chung),서용섭(Yong Sup Seo) 대한핵의학회 1992 핵의학 분자영상 Vol.26 No.1

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

항체의 Cyclic DTPA를 이용한 99mTc 표지시 Polymer 형성과 체내 동태 변화

오옥두(Ok Doo Awh),임상무(Sang Moo Lim),우광선(Kwang Sun Woo),정위섭(Wee Sup Cung) 대한핵의학회 1993 핵의학 분자영상 Vol.27 No.2

N/A Technetium-99m labeling method using bifunctional chelat.ing agent cyclicDTPA has been evaluated with human polyclonal nonspecific IgG. IgG was conjugated with cyclic DTPA with various molar ratio. Reduction of Tc was done with Na,S,O, with various molar excesa Labeling efficiency and identification of polymer was confirmed with HPLC using TSK4000 SW column. Polymer was purified with 100 cm Sepharose 6LB column. Cultured 1x10' Staphylococcus aureus were injected into rat thigh 24 hours later labeled 1gG was injected, and in vivo distribution was observed 4 and 24 hours thereafter. Reduction of 99mTc was optimal with the 10000-50000 times molar excess of Na2S2O4, Polymer formation increased with increasing mloar excess of cyclic DTPA to IgG. Three step labeling-labeling DTPA conjugated IgG after reduction of 99mTc-rnade more polymer than two two step labeling-simultaneous mixing DTPA conjugated IgG, 99mTc and Na2S2O4,. Tc b]ood clearance and lower uptake in the abscess and other organa. IgG conjugated with 200 times molar excess of cyclic DTPA showed slower blood clearance with 200 times molar excess of cyclic DTPA showed slower blaod clearance than that of 200 times molar excess of cyclic DTPA showed slower blood clearance than that of 20 times molar excess. In the 99mTc labeling of IgG with cyclic DTPA for the immunoscintigraphy, obtimalllabeling condition should be chosen, and effect of the ' Tc labeled IgG polymer should be considered.

Methionine 이성질체들의 99mTc 착물 제조 연구

오옥두(Ok Doo Awh),장희순(Hee Soon Chang),이동선(Dong Sun Lee) 대한핵의학회 1992 핵의학 분자영상 Vol.26 No.1

N/A Tc-99m-Methionine complexes from enantiomeric and racemic methionines were prepared controlling reaction parameters such as pH and the concentration of stannous chloride. Some radiochromatographic systems were also examined to determine the labelling yields of Tc-99m complexes. The best resolutions of Tc-99m complexes were obtained at ITLC-SA developed with acetone and paper chromatography with n-butanol saturated with 0.3N HCI. In the former system, HR-Tc-99m and Tc-99m-methionine complex remained at origin, while 99mTcO4 moved with Rf value of 1.0. In latter process, HR-Tc-99m stayed at the origin, while 99mTcO4 and Tc-99m- methionine complexes moved with Rf value of 0.5. By combining of two chromatographic systems, the contents of three Tc-99m species were calculated easily. Tc-99m Labelling from enantiomeric and racemic methionines had little differences and the optimal condition was found at pH 9.00 and the molar ratio of methionine to stannous chloride od 24:1. The yields of Tc-99m complexes from D-, L-, and DL-methionines were 87.6%, 94.1%, and 97.9%, respectively. The results indicated that methionine containing relatively hydrophobic methylthio group (-SCH3) would be labelled with Tc-99m by stannous chloride method.

Taxol의 방사면역측정을 위한 I-125 표지화합물 합성

오옥두(Ok-Doo Awh),금준섭(Jun-Sub Kum),이양호(Yang-He Lee),박용석(Yong-Serk Park),편웅범(Woong-Beum Pyun),최창운(Chang-Hoon Choi) 대한의생명과학회 1997 Biomedical Science Letters Vol.3 No.2

Taxo은 diterpenoid구조를 가진 항암제로서, 난소암과 유방암에 탁월한 효과를 보이지만 다른 항암제와 마찬가지로 독성을 가지고 있어 약물의 체내 혈중농도를 모니터링하는 것이 필요하다. 약물의 혈중농도를 모니터링하는 방법은 HPLC법, ELISA법, RIA법 등이 있으나, RIA법이 민감도 측면에서 또한 간편하다는 점에서 장점이 있다. 본 연구에서는 I-125 표지항원을 이용한 방사면역측정법을 확립하기 위해 먼저 taxol유도체를 합성하였다. 먼저 taxol의 C-13 탄소의 곁가지에 위치한 C-2’부분의 hydroxy기를 succinic anhydride와 반응시켜 2'-hemisuccinyltaxol (Ⅰ)을 합성 (반응수율: 80%)하였다. 또한 tyramine을 ¹²?I로 표지하고 gel chromatography를 통해 정제된 [¹²?I]iodotyramine (Ⅱ) (반응수율: 58%)을 얻었다. (Ⅰ)과 (Ⅱ)를 반응시켜 2’-[¹²?I]iodotyramine-hemisuccinyltaxol (Ⅲ) (반응수율: 96%)을 얻어 ¹²?I 표지창원으로 사용하였다. Taxo에 대한 항체를 획득하기 위해서 (Ⅰ)을 BSA에 접합 반응시켜 2'-hemisuccinyltaxol-BSA접한체를 합성하였으며, 이것을 토끼에 면역주사하여 anti-taxol serum을 얻었다. 이 항체에 대한 역가 검정실험에서 1:20의 회석비에서 B/F(%)가 약 40%를 보였다. 이와 같은 결과는 2-[¹²?I]iodotyramine-hemisuccinyltaxol을 표지항원으로 한 taxol의 방사면역측정 방법으로 혈청내 taxol의 농도측정이 가능함을 제시 해 준다. Taxol, an anticancer drug that has diterpenoid conformation, has been used as an effective chemotherapeutical agent in the treatment of breast and ovarian cancers. Because of its toxicity like other anticancer drugs, monitoring the taxol level in serum is important procedure during cancer therapy. The various monitoring methods using HPLC, ELISA, and RIA have been adopted, and RIA technique is known to be superior than other methods in trems of sensitivity and convenience. In this study, in order to develope taxol RIA system using ¹²?I labelled antigen, first of all we synthesized taxol derivatives. 2'-hemisuccinyltaxol was obtained with about 80% yield by esterification of taxol at C-2' hydroxyl group on C-l3 carbon with succinic anhydride. [¹²?I] iodotyramine was prepared with 58% labelling yield by radioiodination of tyramine and purified by gel chromatography. 2'-[¹²?I]iodotyramine-hemisuccinyltaxol, ¹²?I labelled antigen for taxol RIA, was synthesized with 96% yield from conjugation of 2'-hemisuccinyltaxol and [¹²?I] iodotyramine. Anti-taxol serum was produced from the rabbit immunized with 2'-hemisuccinyltaxol-BSA synthesized by 2'-hemisuccinyltaxol and BSA. The antiserum titer was determined by RIA using 2'-[¹²?I]iodotyramine-hemisuccinyltaxol. The titer of 1:20 was obtained with about 40% of B/T. The results suggest that taxol RIA using ¹²?I labelled antigen can be applied to monitor the taxol level in serum.

간 . 담도계 질환 진단용 99mTc 표지 3 - 요오도 - 2 , 4 , 6 - 트리메틸 이미노 2초산 ( 99mTc - IOTIDA ) 의 제조에 관한 연구

김재록(Jae Rok Kim),오옥두(Ok Doo Awh),박경배(Kyung Bae Park) 대한핵의학회 1990 핵의학 분자영상 Vol.24 No.1

N/A Tc-99m-MAG3 was synthesized, and biodistribution and blood clearance rate were compared with those of 131I-OIH in mice and rats respectively. Finally renal image was obtained from a normal male volunteer before and after prescription of probenecid. The results obtained were as follows: 1) The uptake of Tc-99m-MAG3 by kindey was higher than that of 131I-OIH in mice 10 mins after injection (n=6, p〈0.05), but slightly lower uptakes were found in all organs (kindney, blood, stomach, intestinge and liver) 2 hrs after injection. 2) For Tc-99m-MAG3 t½α=2.4±0.0 min, t½β=44.3±7.4 min, and blood clearance=3.4±0.5 ml/min, and for 131I-OIH t½α=1.8±0.2 min, t½β=69.1±9.5 min, and blood clearance=1.3±0.1 min were found in rats. 3) From the renogram of normal male volunteer, we could find that tmax=130 sec and t½=430 sec before probenecid prescription, and tmax=150∼170sec and t½=810∼1,170 sec after probenecid prescripron. From these results we concluded that Tc-99m-MAG3 can be used instead of 131I-OIH for obtaining renal image.

폐 신티그래피용 99mTc 표지 미소구형 인 혈청 알부민의 제조에 관한 연구

김재록(Jae Rok Kim),오옥두(Ok Doo Awh),박경배(Kyung Bae Park) 대한핵의학회 1989 핵의학 분자영상 Vol.23 No.1

N/A In order to develop technetium-99m-labelled human albumin microsphere (HAM) for lung scintigraphy, various experiments such as preparation and fractionation of HAM, establishment of optimal labelling conditions, determination of radiochemical purity, stability test and biodistribution of Tc-99m-HAM were carried out. HAM was prepared from the suspension of I mi aqueous human serum albumin (25%) in 130 ml of olive oil at 130∼135°with vigorous stirring. The resulting HAM was fractionated with microsieve to get the desired particle size (15∼50 μ) and autoclaved for sterilization. The HAM particles were treated with stannous chloride and the pH of the suspension was adjusted to 3.0∼3.5 with phosphate buffer. After freeze-drying the contents of single reaction vial containing 5 mg of HAM and 0.2 mg of SnCl2 it was reacted with Na99mTcO4. The labelling yield was higher than 99.5% and the stability of Tc-99m-HAM was high enough to maintain 99.1% of radiochemical purity up to 24 hours. Lung and liver uptake in mice was found to be 94% and 0.9%, respectively. Excellent rabbit and human lung scans were also obtained.

부신수실 영상용 131I 표지 메타요오도벤질구아니딘 ( 131I - MIBC ) 의 제조에 관한 연구

김재록(Jae Rok Kim),오옥두(Ok Doo Awh),박경배(Kyung Bae Park) 대한핵의학회 1990 핵의학 분자영상 Vol.24 No.1

N/A To develop 131I-labelled m-iodobenzylguanidine (1311-MIBG), various experiments such as synthesis of MIBG, establishment of labelling conditions, determination of radiochemical purity, and examination of stability were carried out. 1) m-Iodobenzylguanidine (MIBG) sulfate was synthesized with a total yield of 62.4% by the condensation of m-iodobenzylamine hydrochloride with cyanamide via MIBG bicarbonate. Its physical properties, IR, 1H-NMR, and elemental analysis data were nearly identical to those of literature. 2) Freeze-dried or vacuum-dried kit vials were prepared from the mixture so as to contain MIBG (2 mg), ascorbic acid (10 mg), copper (II) sulfate (0.14 mg), and tin (II) sulfate (0.5 mg) per vial. Copper (I) catalyzed radioiodination of MIBG was carried out using kit vials and 0.01 M H2SO4 as solvent at 100℃ for 30 min under nitrogen atmosphere (optimal conditions). Labelling yield was 98% and radiochemical purity was 99.5%, respectively. 3) Solid-phase radioiodination of MIBG was carried out at 155℃ for 30 min using the prepared vials to contain MIBG (2 mg) and ammonium sulfate (10 mg). Duplicate reactions under the same conditions showed labelling yield of 95% and radiochemical purity of 99.5%. MIBG prepared either by catalytic or by solid-phase exchange method showed radiochemical purity of 99% even after 3 days storing at room temperature.

라돈과 그 딸핵종의 피폭에 대한 분진의 영향

조승연(Seung Yon Cho),오옥두(Ok Doo Awh),박신영(Shin Young Park),정양근(Yang Kun Chung),김희근(Hee Kun Kim) 한국환경보건학회 2000 한국환경보건학회지 Vol.26 No.1

Radon progenies existing in indoor air were measured with α spectrometry. The concentrations of 218po, 214Pb, 214Bi and their unattached fractions inside the experimental chamber and Young Kwang Atomic Power Plant were measured with a relative standard deviation of below 50% after the analysis of α spectrum. The results Were compared with the other instrumental methods such as total α count and WL meter. The concentration of radon and the indoor condition were changed intentionally inside the chamber to study the behaviour of radon and radon daughters. Airborne particulates such as tobacco smoke increase equilibrium factor(EF, a major factor of the risk caused by radon) from 1.7 to 2.4 depending on indoor tobacco smoke concentrations. Unattached ratio which is also a important factor for the risk assessment of radon is inversely related to the concentration of indoor tobacco smoke.

99mTc - MDP 제조시 산화방지제 첨가영향

김재록(Jae Rok Kim),오옥두(Ok Doo Awh),박경배(Kyung Bae Park) 대한핵의학회 1992 핵의학 분자영상 Vol.26 No.1

N/A To improve the quality of Tc-99m-methylenediphonate (Tc-99m-MDP) for skeletal imaging, different composed Tc-99m-MDP complexes were prepared with addition of antioxidants such as ascorbic acid, getisic acid, and p-aminobenzoic acid. To characterize the different Tc-99m-MDP preparations, some physical and biochemical properties of Tc-99m-MDP such as thermal stability, lipophilicity and bin-dability to serum protein were studied and organ distribution pattern of these complexes also compared. The therma1 stabilities of Tc-99m-MDP contained antioxidants were dependant mainly on pH, temperature, and elapsed time after the preparation. Tc-99m-MDP complex contained gentisic acid as antioxidant was extremely unstable at alkaline condition. The most stable Tc-99m-MDP was found in the presence of p-aminobenzoic acid. Tc-99m-MDP complexes with antioxidants were very lipophilic but lipophilicity differences in antioxidants were not observed. The bindability of Tc-99m-MDP te serum protein was not affect at pH 5.0∼9.0 by the different antioxidants. However, protein binding percentage of Tc-99m-MDP with ascorbic acid was relatively low (22.7%) at pH 9.0. In biodistribution studies in mice, bone to muscle ratios of Tc-99m-MDPp preparations containing ascorbic acid, gentisic acid, and p-aminobenzoicacid were 15.3, 24.5, and 30.1, respectively Im to our results, p-aminobenzoic acid is fond to be the moat promising antioxidant.