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뇌혈류 영상용 방사성의약품 PRODD의 99mTc 표지 및 생체내분포
고창순(Chang Soon Koh),이명철(Myung Chul Lee),정준기(June Key Chung),이동수(Dong Soo Lee),정재민(Jae Min Jeong),조정혁(Jung Hyuck Cho),오승준(Seung Joon Oh),정수욱(Soo Wook Chung) 대한핵의학회 1995 핵의학 분자영상 Vol.29 No.3
N/A Tc-99m labeled PnAO(propylene amine oxime) derivatives have been widely studied as brain perfusion agents. We synthesized and characterized a PnAO derivative, (RR/SS/meso)-4,8-diaza- 3,9,dimethylundecane-2,l0-dione bisoxime(PRODD). Proton-NMR spectroscopy and thin layer chromatography(silence gel) were performed for its characterization PRODD was 1abeled with Tc- 99m using stannous chloride as reducing agent. The labeling efficiency was determined to be about 85%. Brain uptakes of 4.16±0.42 %ID/g and 3.24±0.13 %ID/g were found after l0min and 30min after intravenous injection. Brain-to-blood ratios were 1.17 and 0.75 at 10 and 30 minutes, which were lower than 1.3 and 1.9 of the ratios with commercial Tc-99m-HMPAO. Autoradiographs of rat brain sections showed the gray matter to white matter ratios of 1.13±0.10 at 30 min after intravenous injection, which was lower than 1.94±0.19 of commercial Tc-99m-HMPAO. With the above findings, we concluded that the lipophilic Tc-99m-PRODD complex was able to cross the blood-brain barrier, however the complex showed lower uptake than Tc-99m-HMPAO in mouse or rat brains. We Could suggest possibility that PRODD could be used as another Tc-99m chelator.
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Dione Bisoxime 계통의 화합물에 대한 테크네슘표지 원리에 관한 연구
고창순(Chang Soon Koh),이명철(Myung Chul Lee),정준기(June Key Chung),이동수(Dong Soo Lee),이경한(Kyung Han Lee),정재민(Jae Min Jeong),곽철은(Cheol Eun Kwark),오승준(Seung Joon Oh),정수욱(Soo Wook Chung),조정혁(Jung Hyuk Cho) 대한핵의학회 1995 핵의학 분자영상 Vol.29 No.1
N/A Tc-99m Labeled hexamethylenepropyleneamineoxime ([Tc-99m-HAMPAO) is a famous amine -oxime compound and is widely used to construct SPECT images of cerebral blood flow. To investigate the relationship between chemical structure and radiolabeling in these kind of diamine -oxime compounds, we synthesized seven compounds by Schiff's base formation and successive reduction with sodium borohydride. They wese (RR/SS)-4,8-diaza-3,6,6,9-tetramethylundecane- 2,10-dione bisoxime (2), (RR/SS/meso)-4,8-diaza-3,9-dimethy-lundecane-2,10-dione bisoxime (4), (RR/SS/meso)-4,8-diaza-3,10-dimethyldodecane-2,11-dione bisoxime (6), (RR/SS/meso)-4,7-diaza- 3,6,6,8-tetramethyldecane-2,9-dione bisoxime (8), (RR/SS/meso)-4,7-diaza-5,6-cyclohexyl-3,8-dime- thyldecane-2,9-dione bisoxime(10),(RR/SS/meso)-3,4-bis (l-aza-2-methyl-3-oxime-l-butyl)-benzoic acid (12), and (RR/SS/meso)-2,3-bis(1-aza-2-methyl-3-oxime-l-butyl) benzophenone (14). Chem- ical structures of al1 the synthesized compounds were identified by taking 1H spectrum. Among them, 2 and 4 are propyleneamine oxime(PnAO), 6 is butyleneamine oxime(BnAO) and 8, 10, 12 and 14 are ethyleneamine oxime (EnAO), Each compound (0.5 mg) was incubated with stannous chloride(0.5 g - 8 g), carbonate-bicarbonate buffer (final concentration = 0.1 M, pH7 - pH 10 ) and Tc-9mm- pertechenate ( 1 ml). Tc-99m labeling of these compounds were checked by ITLC (acetone), ITLC (normal saline), reverse phase TLC (50% acetonitrile) and ITLC (ethyl acetate). According to the results, EnAO's were not labeled by Tc-99m in any of above condition. About 11 % of maximum labeling efficiency was obtained with BnAO. However, 4 (PnAO) was labeled with Tc-99m to 85 % which is similar to the labeling efficiency of 2 (HMPAO). Hydrophilic impurity (9 %) was the most significant problem with the labeling of 4, however, pertechnetate (3 %) and colloid (3 %) were minor problem. In conclusion, we synthesized seven diamine bisoxime compounds, Among them, four EnAO compounds were not labeled by Tc-99m. A BnAO was labeled poor.
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