中华核医学杂志
中華覈醫學雜誌
중화핵의학잡지
CHINESE JOURNAL OF NUCLEAR MEDICINE
2011年
1期
50-53
,共4页
刘晓飞%张锦明%刘长滨%梁涛%周乃康%田嘉禾
劉曉飛%張錦明%劉長濱%樑濤%週迺康%田嘉禾
류효비%장금명%류장빈%량도%주내강%전가화
精氨酸-甘氨酸-天冬氨酸%同位素标记%氟放射性同位素%化学合成%自动化%肿瘤移植%小鼠
精氨痠-甘氨痠-天鼕氨痠%同位素標記%氟放射性同位素%化學閤成%自動化%腫瘤移植%小鼠
정안산-감안산-천동안산%동위소표기%불방사성동위소%화학합성%자동화%종류이식%소서
RGD%Isotope labeling%Fluorine radioisotopes%Chemical synthesis%Automation%Neoplasm transplantation%Mice
目的 研究18F标记RGD多肽的自动化合成方法,并探讨标记物在荷瘤鼠体内的生物学分布情况.方法 在研究了自动化制备N-琥珀酰亚胺-4-18F-氟苯甲酸酯(18F-SFB)的基础上,通过向18F-SFB乙腈溶液中加入RGD多肽、无水DMSO和无水N,N-二异丙基乙胺(DIPEA),充分反应得到18F-氟苯甲酰基(FB)-c(RGDyK),即18F-FB-RGD的粗产品,经HPLC系统梯度分离和固相萃取得到纯品18F-FB-RGD,研究其在荷瘤鼠体内的生物学分布和竞争实验.结果 18F-FB-RGD的标记率为(33.6±3.5)%,合成时间约为110 min,放化纯大于98%.荷瘤小鼠注射18F-FB-RGD后30,60,90和120 min,肿瘤摄取放射性分别为(3.43±0.15)、(2.61±0.14)、(2.11±0.13)、(1.79±0.18)%ID/g,肿瘤/肌肉放射性比值为4.26±0.69至5.80±0.78.用RGD阻断后,肿瘤摄取放射性明显下降,阻断后60 min,阻断组放射性摄取[(0.46±0.21)%ID/g]为非阻断性组[(2.87±0.59)%ID/g]的1/6.结论 18F-FB-RGD是一种有希望的肿瘤显像剂,用国产模块可自动化合成.
目的 研究18F標記RGD多肽的自動化閤成方法,併探討標記物在荷瘤鼠體內的生物學分佈情況.方法 在研究瞭自動化製備N-琥珀酰亞胺-4-18F-氟苯甲痠酯(18F-SFB)的基礎上,通過嚮18F-SFB乙腈溶液中加入RGD多肽、無水DMSO和無水N,N-二異丙基乙胺(DIPEA),充分反應得到18F-氟苯甲酰基(FB)-c(RGDyK),即18F-FB-RGD的粗產品,經HPLC繫統梯度分離和固相萃取得到純品18F-FB-RGD,研究其在荷瘤鼠體內的生物學分佈和競爭實驗.結果 18F-FB-RGD的標記率為(33.6±3.5)%,閤成時間約為110 min,放化純大于98%.荷瘤小鼠註射18F-FB-RGD後30,60,90和120 min,腫瘤攝取放射性分彆為(3.43±0.15)、(2.61±0.14)、(2.11±0.13)、(1.79±0.18)%ID/g,腫瘤/肌肉放射性比值為4.26±0.69至5.80±0.78.用RGD阻斷後,腫瘤攝取放射性明顯下降,阻斷後60 min,阻斷組放射性攝取[(0.46±0.21)%ID/g]為非阻斷性組[(2.87±0.59)%ID/g]的1/6.結論 18F-FB-RGD是一種有希望的腫瘤顯像劑,用國產模塊可自動化閤成.
목적 연구18F표기RGD다태적자동화합성방법,병탐토표기물재하류서체내적생물학분포정황.방법 재연구료자동화제비N-호박선아알-4-18F-불분갑산지(18F-SFB)적기출상,통과향18F-SFB을정용액중가입RGD다태、무수DMSO화무수N,N-이이병기을알(DIPEA),충분반응득도18F-불분갑선기(FB)-c(RGDyK),즉18F-FB-RGD적조산품,경HPLC계통제도분리화고상췌취득도순품18F-FB-RGD,연구기재하류서체내적생물학분포화경쟁실험.결과 18F-FB-RGD적표기솔위(33.6±3.5)%,합성시간약위110 min,방화순대우98%.하류소서주사18F-FB-RGD후30,60,90화120 min,종류섭취방사성분별위(3.43±0.15)、(2.61±0.14)、(2.11±0.13)、(1.79±0.18)%ID/g,종류/기육방사성비치위4.26±0.69지5.80±0.78.용RGD조단후,종류섭취방사성명현하강,조단후60 min,조단조방사성섭취[(0.46±0.21)%ID/g]위비조단성조[(2.87±0.59)%ID/g]적1/6.결론 18F-FB-RGD시일충유희망적종류현상제,용국산모괴가자동화합성.
Objective To evaluate the automatic synthesis of 18F-labeled cyclic RGD peptide c(RGDyK)and its biological distribution in the tumor-bearing mice. Methods N-succinimidyl-4-18 F-fluorobenzoate (18F-SFB) was automatically synthesized and then re-dissolved in acetonitrile (MeCN). The cyclic RGD peptide c(RGDyK) was mixed with an hydrous DMSO and N, N-diisopropyl ethylamine (DIPEA). 18F-FBRGD was obtained by the reaction of peptide solution with 18 F-SFB. The final product was purified by HPLC gradient separation system and solid-phase extraction method. The biodistribution study and competition test of N-4-18F- fluorobenzoyl-RGD (18F-FB-RGD) in the tumor-bearing mice was performed. Results The labeling yield of 18 F-FB-RGD was (33.6 ± 3.5)%. The synthesis time was 110 min. The radiochemical purity was more than 98%. The tumor uptake of 18F-FB-RGD was (3.43 ±0.15), (2.61 ±0.14), (2.11 ±0.13), and (1.79 ±0.18) %ID/g, respectively, at 30, 60, 90 and 120 min after injection. The ratio of tumor to muscle activity ranged from 4.26 ±0.69 to 5.80 ±0.78. The tumor uptake decreased dramatically after RGD blockage. The uptake was (0.46 ±0.21) %ID/g and (2.87 ±0.59) %ID/g in the blocked and unblocked mice, respectively, at 60 min after blockage. Conclusions 18 F-FB-RGD can be automatically synthesized and it may become a promising tumor imaging agent.
