Development of Biologically Active Nucleosides Labeled with Positron Emitting ^<18>F

正电子发射^<18>F标记的生物活性核苷的开发

• 批准号: 01571193
• 负责人: ISHIWATA Kiichi
• 金额: $ 1.34万
• 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 (C)
• 财政年份: 1989
• 资助国家: 日本
• 起止时间: 1989 至 1990
• 项目状态: 已结题
• 来源: https://kaken.nii.ac.jp/grant/KAKENHI-PROJECT-01571193/
• 关键词: F-18; Br-75; Fuluorodeoxyuridine; Bromodeoxyuridine; Tumor Diagnosis; Nucleoside; Nucleic Acid Metabolism; Positron Emission Tomography; フルオロデオキシウリジン; 実験腫瘍; ^<18>F標識化合物; 癌診断

Metabolism of 2-deoxy-5-[^<18>F] fluorouridine (Fdurd), a useful positron emission tomography (PET) tracer of nucleic acid metabolism in tumors, was investigated in tumor-bearing mice and human plasma. Degradation of the tracer in vivo was very rapid. a-[^<18>F] Fluoro-b-alanine (FBAL) wasa main catabolite in the plasma. In tumor tissues, the activated derivatives of FdUrd, FBAL and the other catabolic materials were found; however, contribution of the plasma catabolites to the radioactivity accumulation in the tumor was minor. Nucleic acid metabolism in brain tumors by FdUrd-PET maybe assessed using normal brain regions as a reference.As new radiopharmaceuticals, 5-[^<75>Br] bromouracil (BrUra) and 5-[^<75>Br]bromo-2'-deoxyuridine (BrdUrd) were prepared from ^<75>Br anion and uracil or 2'-deoxyuridine by a chloramine-T method. The ^<75>Br was prepared by the ^<75>As(^3He,3n)^<75>Br reaction. In tumor-bearing rats given each of the tracer, radioactivity increased in tumor tissues. The level for BrdUrd was 2-times higher than that for BrUra. Although debromination was suggested in vivo, it is expected that the accumulation of the tracer in tumors may correlate with DNA synthesis in the t issue.As the other compounds, 5-[^<18>F] fluoro-2', 3'-isopropyridine-5'-0-(4-N-acetamide-2, 4-dideoxy-3, 6, 7, 8-tetra-0-acetyl-1-methoxycarbonyl-D-glycero-a-galacto-octapyranosyl) uridine was prepared using [^<18>F]AcOF or [^<18>F]F_2. But, animal studies of the compound was not done. Labeling of adenosine, guanosine and their derivatives using [^<18>F]AcOF and ^<18>F anion has been done unsuccessfully.

研究了2-脱氧-5-[^<18>F]氟吡啶（Fdurd）在肿瘤中核酸代谢的正电子发射断层扫描（PET）示踪剂在荷瘤小鼠和人血浆中的代谢。示踪剂在体内降解非常迅速。a-[^<18>F]氟-b-丙氨酸（FBAL）是血浆中的主要分解代谢物。在肿瘤组织中发现了FdUrd、FBAL等分解代谢物质的活性衍生物；然而，血浆分解代谢物对肿瘤放射性积累的贡献很小。FdUrd-PET可作为正常脑区的参考，评估脑肿瘤的核酸代谢。5-[^<75>Br]溴嘧啶（BrUra）和5-[^<75>Br]溴-2'-脱氧尿嘧啶（BrdUrd）是新型放射性药物，由^<75>Br阴离子与尿嘧啶或2'-脱氧尿嘧啶经氯胺- t法制备。用^<75>As(^3He,3n)^<75>Br反应制备^<75>Br。在荷瘤大鼠中，给予每一种示踪剂，肿瘤组织中的放射性增加。BrdUrd的含量是BrUra的2倍。虽然在体内已提出脱溴，但预计肿瘤中示踪剂的积累可能与t问题中的DNA合成有关。用[^<18>F]AcOF或[^<18>F]F_2制备了5-[^<18>F]氟-2′，3′-异丙基-5′-0-（4- n -乙酰胺- 2,4 -二脱氧- 3,6,7,8 -四-0-乙酰-1-甲氧羰基-d -甘油-a-半乳糖-八烷基）尿嘧啶。但是，这种化合物的动物实验还没有完成。用[^<18>F]AcOF和^<18>F阴离子对腺苷、鸟苷及其衍生物进行标记是不成功的。

项目成果

K. ISHIWATA, K. SATO, M. KAMEYAMA, T. YOSHIMOTO, T. IDO: "Metabolic Fates of 2'-Deoxy-5-[^<18>F]Fluorouridine in Tumor-Bearing mice and Human Plasma." NUCL. MED. BIOL.(1991)

K. ISHIWATA、K. SATO、M. KAMEYAMA、T. YOSHIMOTO、T. IDO：“荷瘤小鼠和人血浆中 2-Deoxy-5-[^18F]氟尿苷的代谢命运”。

K.Ishiwata,et al.: "Pharmakokinetics of 2'ーdeoxyー[ ^<18>F]fluorouridine in human plasma."

K. Ishiwata等人：“人血浆中2-脱氧-[^ 18 F]氟尿苷的药代动力学”。

K.Ishiwata et al: "Radiotracers for difterentinl in vivo diagnosis of tumor metabolisms."

K.Ishiwata 等人：“用于肿瘤代谢的不同体内诊断的放射性示踪剂。”

K.Ishiwata,T.Takahashi,R.Iwata,et al: "Tumor diagnosis by PET:Poteintial of seven tracers examined in five experimental tumors including an artificial metastasis model." Nuclear Medicine and Biology. (1991)

K.Ishiwata、T.Takahashi、R.Iwata 等人：“PET 肿瘤诊断：在包括人工转移模型在内的五个实验肿瘤中检查的七种示踪剂的潜力。”

K.Ishiwata,K.Sato,M.Kameyama,et al: "Metabolic fates of 2'ーdeoxyー5ー[ ^<18>F]fluorouridine in tumorーbearing mice and huma plasma." Nuclear Medicine and Biology. (1991)

K. Ishiwata、K. Sato、M. Kameyama 等人：“2-脱氧-5-[^ 18 F]氟尿苷在荷瘤小鼠和人血浆中的代谢命运”，1991 年。 ）