Synthesis and evaluation of 76Br labeled compound for tumor diagnosis with PET

76Br标记化合物的合成及PET肿瘤诊断评价

• 批准号: 18591328
• 负责人: IIDA Yasuhiko
• 金额: $ 2.44万
• 依托单位: Gunma University
• 依托单位国家: 日本
• 项目类别: Grant-in-Aid for Scientific Research (C)
• 财政年份: 2006
• 资助国家: 日本
• 起止时间: 2006 至 2007
• 项目状态: 已结题
• 来源: https://kaken.nii.ac.jp/grant/KAKENHI-PROJECT-18591328/
• 关键词: Br-76; PET; tumor; positron labeled antibody; imaging diagnosis; PET診断; がん診断; イメージング

^<18>F-FDG is most valuable tool for tumor diagnosis with PET, but ^<18> F is limited to use for its short half-life, 110 minutes. Usually, radiopharmaceuticals with long half-life are convenient to use. All positron emitters, now using for PET diagnosis, don't suit for labeling of antibody. Compared with these radionuclides, ^<76> Br and ^<64> Cu have appropriate properties ( ^<76> Br: T_<1/2> = 16.1hr, ^<64> Cu: T_1/2 = 12.7hr) and they may have great potentials for immuno-PET. ^<76> Br or ^<64> Cu labeled antibody is suitable for tumor diagnosis. Especially, ^<76> Br is a radioactive halogen such as ^<18> F or ^<123> I, and it is suitable for labeling of various compounds developed for labeling with ^<18> F or ^<123> I. So we hoped to develop radiopharmaceuticals labeled with ^<76> Br for tumor diagnosis with PET. In this study, we synthesized anti-CD20 monoclonal antibody (mAb), NuB2, labeled with ^<76> Br or ^<64> Cu, and evaluated potential for in vivo diagnosis of tumor. Direct … More bromination similar with iodination of proteins has been applied for ^<76> Br labeling of NuB2. For labeling with ^<64> Cu, a stable immunoconjugate was prepared by reacting NuB2 with 1, 4, 8, 11-tetraazacyclotetradecan-N, N', N', N'-tetraacetic acid (TETA), a chelator exhibiting high affinity for ^<64> Cu. For in vivo biodistribution and tumor localization studies in small animals, ^<76> Br or ^<64> Cu labeled NuB2 was prepared and administered to SCID mice bearing CD20+ tumor. We also performed imaging study with PET at 24hr after injection of radiolabeled NuB2. Radiochemical yield of ^<76> Br-NuB2 was approximately 10 % and that of ^<64> Cu-TETA-NuB2 was approximately 90 %. The results of tumor localization studies show that the tumor concentration of radioactivity increased steadily throughout the course of experiment for both compounds, and reached to 10 %dose/g for ^<76> Br-NuB2 and 13 %dose/g for ^<64> Cu-TETA-NuB2 at 2 days. Same results were also obtained from PET studies. In this study, we successfully prepared radiolabeled mAbs for PET, exhibiting high affinity for CD20+ tumor. ^<76> Br-NuB2 and ^<64> Cu-TETA-NuB2 were highly accumulated to tumor, and PET could show these images clearly, which were same results with ex vivo studies. Lower tumor uptake of ^<76> Br-NuB2 than that of ^<64> Cu-TETA-NuB2 seems to be owing to dehalogenation. From these data, the use of ^<76> Br and ^<64> Cu for immuno-PET has great potential for tumor diagnosis. Less

^ 18 F-FDG是PET诊断肿瘤最有价值的工具，但^ 18 F因其半衰期短（110分钟）而受到限制，通常半衰期长的放射性药物使用起来很方便。目前用于 PET 诊断的所有正电子发射体都不适合标记抗体，与这些放射性核素相比，^<76> Br 和 ^<64> Cu 具有适当的特性（ ^<76> Br: T_<1/2> = 16.1hr, ^<64> Cu: T_1/2 = 12.7hr) 并且它们可能具有免疫PET的巨大潜力。 Cu标记的抗体适用于肿瘤诊断。特别地，^ 76 Br是放射性卤素，例如^ 18 F或^ 123 I，它适用于标记^<18>F或^<123>I标记的各种化合物。因此我们希望开发出^<76>Br标记的放射性药物用于PET诊断肿瘤。抗 CD20 单克隆抗体 (mAb)、NuB2，用 ^<76> Br 或 ^<64> Cu 标记，并评估了体内直接诊断肿瘤的潜力……更多与蛋白质的碘化类似的溴化已应用于NuB2的^ 76 Br标记。为了用^ 64 Cu标记，通过使NuB2与1,4,8,11-四氮杂环十四烷-N,N反应来制备稳定的免疫缀合物。 ',N',N'-四乙酸(TETA)，一种对体内^ 64 Cu表现出高亲和力的螯合剂。小动物中的生物分布和肿瘤定位研究，制备^ 76 Br或^ 64 Cu标记的NuB2并将其施用给携带CD20+肿瘤的SCID小鼠。我们还在注射放射性标记的NuB2后24小时用PET进行成像研究。 ^<76>Br-NuB2 的含量约为 10%，^<64>Cu-TETA-NuB2 的含量约为 90%肿瘤定位研究的结果表明，两种化合物的肿瘤放射性浓度在整个实验过程中稳定增加，并且^ 76 Br-NuB2达到10％剂量/g，^ 76 Br-NuB2达到13％剂量/g。 <64> 2天时的Cu-TETA-NuB2也从PET研究中获得了相同的结果。在本研究中，我们成功地制备了用于PET的放射性标记的mAb，其对PET表现出高亲和力。 CD20+肿瘤。^<76>Br-NuB2和^<64>Cu-TETA-NuB2在肿瘤中高度积累，并且PET可以清楚地显示这些图像，这与^<76较低的肿瘤摄取的结果相同。 > Br-NuB2 比 ^<64> Cu-TETA-NuB2 似乎是由于脱卤作用。从这些数据来看，^<76> 的使用。 Br 和 ^<64> Cu 用于免疫 PET 在肿瘤诊断方面具有巨大潜力。

项目成果

Present role and future prospects of positron emission tomography in clinical oncology

• DOI: 10.1111/j.1349-7006.2006.00341.x
• 发表时间: 2006-12-01
• 期刊: CANCER SCIENCE
• 影响因子: 5.7
• 作者: Oriuchi, Noboru;Higuchi, Tetsuya;Endo, Keigo
• 通讯作者: Endo, Keigo

Early diagnosis of recurrent hepatocellular carcinoma with 18F-FDG PET after radiofrequency ablation therapy

18F-FDG PET早期诊断射频消融治疗后复发性肝细胞癌

• 发表时间: 2008
• 期刊: Ann Nucl Med 22(1)
• 作者: Paudyal B;Miyakubo M;et.al. (他7名);Paudyal B
• 通讯作者: Paudyal B

Chemical design of a radiolabeled gelatinase inhibitor peptide for the imaging of gelatinase activity in tumors

• DOI: 10.1016/j.nucmedbio.2007.04.002
• 发表时间: 2007-07-01
• 期刊: NUCLEAR MEDICINE AND BIOLOGY
• 影响因子: 3.1
• 作者: Hanaoka, Hirofurni;Mukai, Takahiro;Saji, Hideo
• 通讯作者: Saji, Hideo

Early diagnosis of recurrent hepatocellular carcilloma with 18F-FDG PET after radiofrequency ablation therapy

18F-FDG PET早期诊断射频消融治疗后复发性肝细胞癌

• 发表时间: 2007
• 期刊: Oncol Rep 18
• 作者: 成瀬昭二;平澤泰介;勝見泰和;田中忠蔵;Miyakubo M;Hanaoka H.;Paudyal B;Miyakubo M;Hanaoka H;Paudyal B;Miyakubo M;Hanaoka H;Paudyal B
• 通讯作者: Paudyal B

Br-76 or Cu-64 1abeled antibody for immuno-PET in quantitative evaluation of radioimmunotherapy.

Br-76 或 Cu-64 1 标记抗体，用于放射免疫治疗定量评估中的免疫 PET。

• 发表时间: 2007
• 作者: 成瀬昭二;平澤泰介;勝見泰和;田中忠蔵;Miyakubo M;Hanaoka H.;Paudyal B;Miyakubo M;Hanaoka H;Paudyal B;Miyakubo M;Hanaoka H;Paudyal B;Oriuchi N;Endo K;H. Hanaoka;Oriuchi N;Endo K;H. Hanaoka;H.Hanaoka;Iida Y
• 通讯作者: Iida Y