CAJ | 학술논문

目的用改良法合成β淀粉样蛋白(AB)显像剂2-(4'-N-11C-甲胺苯基)-6-羟基苯并噻唑(N-11CH3-6-OH-BTA-1),并评价其生物学性质.方法采用改良法合成N-11CH3-6-OH-BTA-1,即"C-CH3-Triflate与1～2 mg的6-OH-BTA4)(前体)丙酮溶液在-20℃下捕获,80℃反应,再经高效液相色谱仪(HPLC)纯化,固相萃取分离.同时用常规法合成N-11CH3-6-OH-BTA-1,比较2种方法的合成效率.研究NH正常小鼠体内N-11CH3-6-OH-BTA-1的生物学分布.选阿尔茨海默病(AD)患者1例,健康志愿者1名,研究N-11CH-6-OH-BTA-1在其体内的摄取及清除.结果改良法的不校正合成效率为29.8%(合成次数n=22),与常规法(30.2%,合成次数n=3)接近,但前体量<1 mg,效率下降至14%.改良法产品放化纯>95%,比活度为18.0 TBq/mmol.NH小鼠脑摄取N-11CH3-6-OH-BTA-1较多,2 min每克组织百分注射剂量率(%ID/g)达(5.46±1.06)%ID/g;清除快,30 min时为(0.22±0.02)%ID/g.AD患者在注射N-11CH3-6-OH-BTA-1后45 min时,颞叶及枕叶有明显的放射性滞留,而健康志愿者45 min时脑内放射性基本清除.结论改良法合成N-11CH3-6-OH-BTA-1可降低前体用量.N-11CH3-6-OH-BTA-1有可能成为临床AD诊断及治疗中评价Aβ分布的显像剂.
목적 용개량법합성β정분양단백(AB)현상제2-(4'-N-11C-갑알분기)-6-간기분병새서(N-11CH3-6-OH-BTA-1),병평개기생물학성질.방법 채용개량법합성N-11CH3-6-OH-BTA-1,즉"C-CH3-Triflate여1～2 mg적6-OH-BTA4)(전체)병동용액재-20℃하포획,80℃반응,재경고효액상색보의(HPLC)순화,고상췌취분리.동시용상규법합성N-11CH3-6-OH-BTA-1,비교2충방법적합성효솔.연구NH정상소서체내N-11CH3-6-OH-BTA-1적생물학분포.선아이자해묵병(AD)환자1례,건강지원자1명,연구N-11CH-6-OH-BTA-1재기체내적섭취급청제.결과 개량법적불교정합성효솔위29.8%(합성차수n=22),여상규법(30.2%,합성차수n=3)접근,단전체량<1 mg,효솔하강지14%.개량법산품방화순>95%,비활도위18.0 TBq/mmol.NH소서뇌섭취N-11CH3-6-OH-BTA-1교다,2 min매극조직백분주사제량솔(%ID/g)체(5.46±1.06)%ID/g;청제쾌,30 min시위(0.22±0.02)%ID/g.AD환자재주사N-11CH3-6-OH-BTA-1후45 min시,섭협급침협유명현적방사성체류,이건강지원자45 min시뇌내방사성기본청제.결론 개량법합성N-11CH3-6-OH-BTA-1가강저전체용량.N-11CH3-6-OH-BTA-1유가능성위림상AD진단급치료중평개Aβ분포적현상제.
Objective Assessing the deposition of β-amyloid (Aβ) in the living brain is important for diagnosis and treatment of Alzheimer's disease (AD). The synthesis of 2-(4'-N-11 C-methylaminophenyl)-6-hydroxybenzothiazole (N-11CH3-6-OH-BTA-1), a potential positron labeled probe for imaging Aβ, was described in this study. Methods N-11CH36-OH-BTA-1 was synthesized with an improved method using 1-2 mg 6-OH-BTA-O as precursor. It was reacted with 11C-methyl Triflate in acetone cooled to -20℃; then the reactor was heated to 50℃ for 1 min, and the product transferred to preparative radio high-pressure liquid chromatograph (HPLC) system for purification by solid-phase extraction. N-11CH3-6-OH-BTA-1 was also synthesized by the conventional method with 5-8 nag precursor. The synthesis yield using both methods was compared. The biodis-tribution in normal Nit mice was studied. The imaging studies of N-11CH3-6-OH-BTA-1 were performed in one patient with known diagnosis of AD and in one healthy control subject. Results The synthesis yield was simi-lar between the two methods [29.8% (n=22) by improved method and 30.2% (n=3) by conventional method], but the amount of precursor used was less with the improved method. When the precursor used was <1 mg, the synthesis yield decreased to 14%. The radiochemical yield was over 95%, and the specif-ic activity was 18.0 TBq/mmol. The radioactivity was accumulated in liver and kidneys after intravenous in-jection of N-11CH3-6-OH-BTA-1. In the normal NH mice brain, the uptake of N-11CH3-6-OH-BTA-1 [per-centage activity of injected dose per gram of tissue (% ID/g)] was high at 2 min [(5.46±1.06) % ID/g].The washout of brain activity was fast[(0.22±0.02) %ID/g at 30 min]. In the AD patient, activity was in-creased most prominently in temporal cortex and occipital cortex after 45 rain. In the control subject, there was no abnormal uptake in the same cortical areas. Conclusions The improved method requires less amount of precursors in the synthesis of an equivalent yield of N-11CH:6-OH-BTA-1. N-11CH36-OH-BTA-1 can be used as an agent for detection of brain Aβ deposition in patients with AD.