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

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^<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