Synthesis of Biologically Active Heterocyclic Compounds Labelled with Positron Emitting Radionuclides for Diagnoses of Diseases of Brain and Heart and Cancer

正电子发射放射性核素标记的生物活性杂环化合物的合成，用于诊断脑、心脏疾病和癌症

• 批准号: 04454291
• 负责人: TADA Masao
• 金额: $ 4.03万
• 依托单位: Tohoku University
• 依托单位国家: 日本
• 项目类别: Grant-in-Aid for General Scientific Research (B)
• 财政年份: 1992
• 资助国家: 日本
• 起止时间: 1992 至 1994
• 项目状态: 已结题
• 来源: https://kaken.nii.ac.jp/en/grant/KAKENHI-PROJECT-04454291/
• 关键词: Synthesis; [fluoroacetyl-^<18>F] Fluoromelatonin; [^<18>F] Fluoride; Cyclotron; Radioactive isotope; N^<omega>- [^<18>F] Fluoroacetylserotonin; N^ω-^<18>F]フルオロアセチルセロトニン; [fluoroacetyl-^<18>F]フルオロメラトニン; 診断; 2-デオキシ-2-[^<18>F]フルオロ-D-ガラクトース; 陽電子放出核種

An efficient synthesis of [fluoroacetyl-^<18>F] fluoromelatonin (N^<omega>- [^<18>F] Fluoroacety1-5-methoxytryptamine) starting from [^<18>F]fluoride has been established. [^<18>F] Fluoride was produced by the ^<18>O (p, n)^<18>F nuclear reaction from a circulating 20%-enriched [^<18>O] water target using the Tohoku University Cyclotron. The ^<18>F nuclide thereby formed was converted to potassium [^<18>F] fluoride. The reaction of[^<18>F]fluoride with ethyl p-toluenesulfonyloxyacetate derived from ethyl bromoacetate with silver p-toluenesulfonate afforded ethyl [^<18>F] fluoroacetate, which was then hydrolyzed with alkali and condensed with 5-methoxytryptamine in the presence of dicyclohexylcarbodiimide to give the desired radioactive isotope in a 26.7% radiochemical yield. The purity, specific activity and the total time required for its synthesis are>98%, 540 mCi/mumol and ca.90 min, respectively.N^<omega>- [^<18>F] Fluoroacetylserotonin was synthesized under similar conditions in 22.6% radiochemical yield. The purity and specific activity of the hormone are>98% and 600 mCi/mumol, respectively.

建立了一种以[^ F]氟化物为原料合成[氟乙酰-^<18>F]氟褪黑素（N^<omega>- [^<18>F] Fluoroacetyl-5-methoxytryptamine）<18>的有效方法。[^<18>F]氟化物是使用东北大学回旋加速器，从循环的20%浓缩[^ O]水靶中通过^<18>O（p，n）^<18>F核反应产生<18>的。由此形成的^<18>F核素转化为氟化钾[^<18>F]。由<18>溴代乙酸乙酯与对甲苯磺酸银反应生成对甲苯磺酰氧基乙酸乙酯，再与[~（14）F]氟反应生成[~（14）<18>F]氟乙酸乙酯，然后用碱水解，在二环己基碳二亚胺存在下与5-甲氧基色胺缩合，得到目标放射性同位素，放化产率为26.7%。其纯度&gt; 98%，比活度为540 mCi/mumol，合成所需总时间约90 min，在类似条件下合成了N^<omega>- [^<18>F]氟乙酰5-羟色胺，放化产率为22.6%。该激素的纯度和比活性分别为&gt;98%和600 mCi/mumol。

项目成果

Masao Tada,Ren Iwata,Hiroshi Sugiyama et al.: "An Efficient Synthesis of N^ω-[^<18>F]-Fluoroacetylserotonin(N^ω-[^<18>F]-Fluoroacetyl‐5‐hydroxytryptamine)" J.Labelled Compds.Radiopharm.34. 741-746 (1994)

Masao Tada、Ren Iwata、Hiroshi Sugiyama 等人：“N^ω-[^<18>F]-氟乙酰血清素（N^ω-[^<18>F]-氟乙酰基-5-羟色胺）的高效合成” J.Labeled Compds.Radiopharm.34。741-746 (1994)

Masao Tada, Ren Iwata, Hiroshi Sugiyama, Kazunori Sato, Hiroshi Fukuda, Kazuo Kubota, Roko Kubota, Hiromu Takahashi, Akira Wakui, Yoshinao Abe, Takehiko Fujiwara, Tachio Sato, and Tatsuo Ido: "A Rapid One-pot Synthesis of [fluoroacetyl-^<18>F] Fluoromelat

Masao Tada、Ren Iwata、Hiroshi Sugiyama、Kazunori Sato、Hiroshi Fukuda、Kazuo Kubota、Roko Kubota、Hiromu Takahashi、Akira Wakui、Yoshinao Abe、Takehiko Fujiwara、Tachio Sato 和 Tatsuo Ido：“[氟乙酰基的快速一锅合成”

Masao Tada: "A Rapid One-pot Synthesis of [fluoroacetyl-^<18>F]Fluoromelatonin" CYRIC Ann.Rep.(Tohoku Univ.). 1992. (1993)

Masao Tada：“[氟乙酰基-^ 18 F]氟褪黑激素的快速一锅合成”CYRIC Ann.Rep.(东北大学)。

"A Rapid Synthesis of[fluoroacetyl-^<18>F]Fluoromelatonin(N^ω-[^<18>F]Fluoroacetyl‐5‐methoxy‐tryptamine),a Potential Diagnostic Imaging Agent" J.Labelled Compds.Radiopharm.33. 601-606 (1993)

“快速合成[氟乙酰基-^18F]氟褪黑素（N^ω-[^18F]氟乙酰基-5-甲氧基-色胺），一种潜在的诊断成像剂”J.Labeled Compds.Radiopharm.33 .601-606 (1993)

Masao Tada: "A Rapid Synthesis of[fluoroacetyl-^<18>F]Fluoromelatonin(N^ω-[^<18>F]Fluoroacetyl-5-methoxytryptamine),a Potential Diagnostic Imaging Agent" J.Labelled Compds.Radiopharm.33. 601-606 (1993)

Masao Tada：“一种潜在的诊断成像剂[氟乙酰基-^ 18 F]氟褪黑素(N^ω-[^ 18 F]氟乙酰基-5-甲氧基色胺)的快速合成”J.Labeled Compds.Radiopharm。 33.601-606 (1993)