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1.
Eigo Otsuji Toshiharu Yamaguchi Nobuki Yamaoka Katsunori Taniguchi Makoto Kato Tatsuya Kotani Kazuya Kitamura Toshio Takahashi 《Cancer science》1994,85(5):530-535
In this study, we conjugated chimeric Fab fragments of the monoclonal antibody (MAb) A7, which reacts with pancreatic cancers, to the antitumor drug neocarzinostatin (chA7Fab-NCS) and intravenously injected 125 I-labeled chA7Fab-NCS into nude mice bearing a human pancreatic cancer xenograft. We compared the tumor localization of 125 I-labeled chA7Fab-NCS with that of conventional 125 I-labeled A7-NCS, which was produced by conjugation of MAb A7 and NCS. 125 I-Labeled chA7Fab-NCS accumulated in the tumor earlier than 125 I-labeled A7-NCS, and significantly larger amounts of 125 I-labeled chA7Fab-NCS had accumulated in the tumor 1 hour after injection. The results suggest that chA7Fab may be a suitable carrier for NCS in immunotargeting therapy against pancreatic cancer. 相似文献
2.
Eigo Otsuji Toshiharu Yamaguchi Kazuhito Yamamoto Hiroomi Matsumura Hiroshi Tsuruta Yoshihiro Yata Hiroshi Nishi Kazuma Okamoto Kazuya Kitamura Toshio Takahashi 《Cancer science》1997,88(2):205-212
Murine monoclonal antibodies (mAbs) such as A7 administered to humans induce a human anti-mouse antibody response. Moreover, because Fab fragments of mAbs are able to penetrate target tumors easily, they may be more suitable than intact mAb to be carriers of anticancer agents such as neocarzinostatin (NCS), which are rapidly inactivated in the blood. To address these problems, chimeric A7 Fab fragment-NCS conjugate (chA7Fab-NCS) was produced. However, large amounts of 12S I-labeled chA7Fab-NCS accumulate in the kidney and can lead to renal dysfunction. To decrease renal accumulation of chA7Fab-NCS, chA7Fab was biotinylated and administered with a subsequent injection of avidin. Human pancreatic carcinoma-bearing nude mice were injected with 125 I-labeled biotinylated chA7Fab-NCS with or without subsequent administration of avidin. The accumulation of 125 I-labeled biotinylated chA7Fab-NCS in tissue samples was measured at appropriate time intervals. 12S I-labeled biotinylated chA7Fab-NCS was cleared more rapidly from the blood and the kidney with the administration of avidin than without it. There was no difference between tumor accumulation in these groups. The tumor/blood ratio of radioactivity of 125 I-labeled biotinylated chA7Fab-NCS was significantly higher with subsequent administration of avidin than without avidin. The administration of biotinylated chA7Fab-NCS followed by avidin may enhance safety and permit the administration of larger doses of NCS without the subsequent development of renal failure. A larger amount of 12S I-labeled biotinylated chA7Fab-NCS was retained in the liver and spleen with the subsequent administration of avidin than without avidin 相似文献
3.
Hiroshi Nishi Toshiharu Yamaguchi Eigo Otsuji Tatsuya Kotani Katsunori Taniguchi Kazuma Okamoto Yoshihiro Yata Hiroshi Tsuruta Toshio Takahashi 《Cancer letters》1997,120(2):127-134
Clear immunoscintigraphy with radiolabeled monoclonal antibodies (MAbs) requires a high tumor tissue/blood ratio of radioactivity. In this study, we attempted to obtain a high tumor tissue/blood ratio by the active removal of radiolabeled MAb from the circulation, using the avidin–biotin system. Biotinylated 125I-labeled MAb A7 was injected intravenously into nude mice bearing a human colon cancer (WiDr) xenograft. Avidin was injected 24 h later. The tumor tissue/blood ratio of radioactivity was almost four times that of controls. These results suggest that biotinylated 125I-labeled MAb A7 and avidin are potentially useful for the rapid immunodetection of human colon cancer. 相似文献
4.
Takashi Kamigaki Masahiro Yamamoto Harumasa Ohyanagi Masato Ohya Takao Shimazoe Akira Kono Wataru Ohtani Yuji Narita Masahiro Ohkubo Yoichi Saitoh 《Cancer science》1995,86(12):1216-1223
Recombinant mouse/human chimeric monoclonal antibody A10 (ch-A10) and its Fab fragment (ch-Fab) react with carcinoembryonic antigen on various gastrointestinal carcinomas. We performed biodistribution studies with 125 I-labeled ch-Al0 and ch-Fab in an antigen-positive human pancreatic carcinoma (BxPC-3) xenograft model. We also evaluated the anti-tumor effect of 131 I-labeled ch-Al0 and studied the detection of BxPC-3 xenografts with 123 I-labeIed ch-Fab in whole body scintigraphy. In comparative biodistribution studies, the tumor uptake of 125 I-labeled ch-Al0 was significantly greater than that of 125 I-labeIed ch-Fab 24 h post-injection. However, the tumor-to-blood ratio was 46.8 for ch-Fab at 24 h post-injection, while it was only 1.4 for ch-Al0. Microautoradiography studies showed that ch-Fab penetrated more uniformly into the tumor nodules than did ch-Al0. In mice given a therapeutic dose of 131 I-labeled ch-AlO, a significant inhibition of tumor growth was seen, while control I31 l-labeled human IgG did not affect tumor growth. Leukocyte toxicity was observed within 3 weeks after injection of 131 I-labeled ch-Al0, but leukocyte counts recovered to normal levels at 8 weeks post-injection. In whole-body scintigraphy, clear and rapid tumor imaging was obtained with 200 (Ci of 123 I-labeled ch-Fab 24 h post-injection. These results suggest that radioiodine-labeled chimeric A10 antibodies could potentially be useful candidates for radioimmunotherapy and radio-immunodetection of pancreatic carcinomas. 相似文献
5.
Akimasa Inui Yong-Suk Chung Tetsuji Sawada Yasuyuki Kondo Jenny J. L. Ho Young-S. Kim Michio Sowa 《Cancer science》1996,87(9):977-984
We investigated the biodistribution, radiolocalization, and radioimmunotherapeutic potential of 131 I-labeled Nd2 in athymic nude mice bearing human pancreatic carcinoma xenografts. 131 I-Nd2 was accumulated at high levels in the tumor, in contrast to blood, liver, spleen, and other normal organs. The tumor was clearly delineated in scintigraphs. The volumes of tumors of mice injected with 7.4 MBq of 131 I-Nd2 were 80% less than those of tumors before injection of radiolabeled Nd2. Fibrous or vacuolar degeneration was seen in histological sections of tumors of 7-week-treated mice. The growth of tumors in mice treated with misonidazole, a hypoxic cell radiosensitizer, and then injected twice with 3.7 MBq of 131 I-Nd2 was suppressed over 7 weeks. Neither leucocytopenia nor thrombocytopenia was severe after injection of radiolabeled Nd2. Thus 131 I-labeled Nd2 may have clinical application in the radioimmunotherapy of pancreatic cancer. 相似文献
6.
Eigo Otsuji Toshiharu Yamaguchi Hiroshi Tsuruta Yoshihiro Yata Hiroshi Nishi Kazuma Okamoto Katsunori Taniguchi Makoto Kato Tatsuya Kotani Kazuya Kitamura Toshio Takahashi 《Journal of surgical oncology》1996,61(2):149-154
Two types of fragments of MAb A7 were produced to improve the efficacy and safety in targeting chemotherapy with neocarzinostatin. In this study, 125I-labeled F(ab′)2 and Fab fragments of MAb A7 and 125I-labeled MAb A7 were injected intravenously into mice with pancreatic carcinoma xenografts, and the accumulation of each antibody in the tumors was compared. A greater amount of the 125I-labeled Fab fragments of MAb A7 localized in the tumor 2 h following the injection than was observed with the other probes. Relatively less 125I-labeled MAb A7 localized in the tumor 2 h following the injection than was observed with the other two probes. Moreover, reaction of rabbit antimouse IgG with the Fc portion, which is the most immunopotent region of the Fab and F(ab′)2 fragments of MAb A7 and MAb A7, was determined by ELISA; the weakest reaction was observed with the Fab fragments of MAb A7. These results suggest that the Fab fragments of MAb A7 may be more suitable carriers of an anti-cancer drug that is inactivated rapidly in the blood, such as NCS, in targeting chemotherapy than either intact MAb A7 or the F(ab′)2 fragments of MAb A7. © 1996 Wiley-Liss, Inc. 相似文献
7.
Hisataka Kobayashi Bao-Fu Sun Eui-Sik Han Meyoung-Kon Kim Nhat Le Qing-Cheng Wang David L. Nelson Ira Pastan Thomas A. Waldmann Chang H. Paik Jorge A. Carrasquillo 《Cancer science》1998,89(4):436-444
Prior in vivo studies using the 125 I-labeled anti-Tac disulfide-stabilized variable region fragment (125 I-anti-Tac dsFv) of monoclonal antibody in the presence of the circulating soluble alpha subunit of the interleukin-2 receptor (sIL-2Rα) have shown formation of complexes which interfere with biodistribution. In this study we evaluated the effects of preinjecting HuTac and 7G7/B6, two immunoglobulin Gs (IgGs) that recognize different epitopes of sIL-2Rα, on the biodistribution of 125 I-anti-Tac dsFv in mice bearing SP2/Tac tumor xenografts, which produce sIL-2Rα, or on nude mice injected with 500 ng of sIL-2Rα. We also evaluated the biodistribution in mice of 125 I-labeled sIL-2Rα injected alone or with HuTac and 7G7/B6. Injection of either HuTac or 7G7/B6 resulted in complexes with the sIL-2Rα in serum. Injection of HuTac before 125 I-anti-Tac dsFv, in SP2/Tac tumor-bearing mice, resulted in faster clearance of the dsFv from the blood (7.6%ID/g at 30 min), compared to 23.2%ID/g for the no-antibody control; preinjection of 7G7/B6 prolonged the retention of 125 I-anti-Tac dsFv to 35.3%ID/g, with more complexes in serum. In mice pre-injected with 7G7/B6 the concentration of 125 I-anti-Tac dsFv in tumor was lower (5.2±0.3%ID/g) than in mice preinjected with HuTac (7.9±1.2%ID/g) or in the control group (5.6±0.7%ID/g). In conclusion, while both IgGs formed complexes with sIL-2Rα and prolonged its retention, preinjection of 7G7/ B6 was detrimental, because the increased circulating sIL-2Rα still had the epitope recognized by the dsFv available for binding and neutralized the anti-Tac dsFv upon injection, whereas preinjection of HuTac blocked the epitope. 相似文献
8.
Tsuyoshi Satoh Tadashi Watanabe Masanori Tadokoro Junichi Sakamoto Hiroki Murayama Katsuki Itoh Sadayuki Sakuma Hiroshi Takagi 《Cancer science》1992,83(4):379-386
Anti-carcinoembryonic antigen monoclonal antibody (MAb) CEA102 was produced by immunization with purified CEA and the specific accumulation of radiolabeled CEA102 in colorectal cancers was investigated by autoradiography of surgical specimens using Fuji Computed Radiography (FCR). Five patients with colorectal cancer were injected intravenously with 131 I-labeled intact CEA102 or its F(ab')2 . Primary tumor and liver metastases were successfully detected by external scanning with a gamma camera in 4 cases. Autoradiographic study of the surgical specimens using FCR showed predominant localization of 131 I-labeled CEA102 in primary tumors and liver metastases in all cases. Even a small liver metastasis (0.5 cm) was clearly visualized in the autoradiogram by FCR. The pixel distribution curves of the density of the respective tissues in the autoradiograms by FCR showed the heterogeneity of the distribution of administered radiolabeled MAb in individual tumors, but the density of the tumors was higher than that of the normal tissues. In the quantitative distribution analysis of CEA102, the uptake of the primary tumor (mean 1.10%ID/kg) was ten-fold greater than that of the normal colon mucosa (mean G.10%ID/kg). These results revealed that the application of MAb has great potential in radioimmunodetection as well as in antibody-directed therapy. 相似文献
9.
Eigo Otsuji Toshiharu Yamaguchi Nobuki Yamaoka Tatsuya Kotani Hiroshi Tsurumi Kazuya Kitamura Nozomi Yamaguchi Toshio Takahashi 《Journal of surgical oncology》1993,53(3):168-174
Much recent research has been directed toward the use of monoclonal antibodies (MoAbs) for the immunodetection of solid tumors. In pancreatic cancer, conventional immunoscintigraphy using intact MoAbs remains disappointing. In this study, 125I-labeled F(ab')2 fragments produced by pepsin digestion of MoAb A7 were injected intravenously into nude mice bearing human pancreatic cancer, HPC-YS, xenografts that have previously been shown to react specifically with MoAb A7. The tumor tissue/blood ratio of 125I-labeled F(ab')2 fragments of MoAb A7 increased with time and was much higher than those for normal tissues. Moreover, the tumor tissue/blood ratio of 125I-labeled F(ab')2 fragments was greater than that of intact MoAb A7, although the F(ab')2 accumulation was less than that of intact MoAb A7 in the tumor. These results suggest that F(ab')2 fragments of MoAb A7 may be suitable carriers of radionuclides for immunodetection of human pancreatic cancer. © 1993 Wiley-Liss, Inc. 相似文献
10.
Akifumi Takaori-Kondo Makoto Hosono Kazunori Imada Zheng-Sheng Yao Harumi Sakahara Hirohiko Yamabe Junji Konishi Minoru Okuma Takashi Uchiyama 《Cancer science》1995,86(3):322-328
To clarify the mechanism of in vivo proliferation of adult T cell leukemia (ATL) cells, we examined the organ distribution of ATL-43T cell line cells derived from original leukemic cells in severe combined immunodeficiency (SCID) mice using radiometric techniques. First, we injected 111 In-oxine-labeled ATL-43T cells into SCID and CB17 mice. On day 6, significant accumulation of radioactivity was found in the spleen and thymus of SCID mice (33.3±9.4 and 10.0±3.6 % injected dose/g of tissue [%ID/g], respectively) in comparison with that in CB17 mice (19.1±2.5 and 3.7±0.9 %ID/g, respectively). Next, we injected radiolabeled anti-Tac monoclonal antibody (MoAb) recognizing human interleukin-2 receptor (IL-2R) α chain or isotype-matched control MoAb RPC5 in SCID mice bearing ATL-43T cells 4 weeks after cell inoculation. The amounts of radioactivity found in the spleen and thymus of SCID mice injected with 125 I-labeled anti-Tac MoAb (22.5±6.9 and 22.8±9.6 %ID/g, respectively) were significantly higher than those in the corresponding organs of SCID mice injected with 125 I-labeled RPC5 MoAb (12.0±5.1 and 7.5±4.6 %ID/g, respectively). Similar results were obtained with 111 In-labeled anti-Tac MoAb. These results were consistent with the histological findings of SCID mice bearing ATL-43T cells, indicating that ATL-43T cells infiltrated preferentially into the lymphoid organs, such as the spleen and thymus, and proliferated there. Thus, the radiometric techniques employed in this study were very useful to evaluate the proliferation sites of ATL-43T cells in SCID mice. Furthermore, this murine model could give us an opportunity to test the feasibility of therapeutic application of radiolabeled anti-Tac MoAb. 相似文献
11.
Monoclonal antibody (MAb) 15 and its F(ab')2 and Fab fragments were radioiodinated, and their biodistribution and imaging were compared in BALB/c nude mice bearing a xenograft of a human lung cancer (TKB-2). Association constants for 125I-labeled MAb 15 IgG, F(ab')2, and Fab were 1.9 X 10(9), 1.8 X 10(9), and 3.7 X 10(8) M-1, respectively. Immunoreactive fractions ranged from 0.59 to 0.50. Cultured TKB-2 cells expressed 1.1 X 10(4) binding sites/cell for MAb 15 IgG in vitro. The binding of a control antibody and the binding of its fragments to TKB-2 cells were less than 3% of the input doses. The mice with the TKB-2 tumors were given simultaneous injections of 10 microCi of 131I-labeled MAb 15 or its fragments and 10 microCi of 125I-labeled control IgG or its fragments. With MAb 15 IgG, the percentage of the injected dose bound per gram of tissue (ID/g) of the tumor was 3.68% at day 7, when the localization index (LI) was 4.38. At day 2 after MAb 15 F(ab')2 injection, 1.12% of the ID/g was localized in the tumor and the LI was 3.04. After MAb 15 Fab injection, the percentage of the ID/g of the tumor was 0.31% and the LI was 2.58 at day 1. MAb 15 IgG, F(ab')2, and Fab cleared from the blood early, with a half-life of 33, 16, and 9 hours, respectively. The distributions of MAb 15 and its fragments in the normal organs did not differ from those of the control. Radioimaging with 100 microCi of 131I-labeled MAb 15 and its fragments showed that 42%, 44%, and 32% of the total-body count were localized in the tumor with IgG at day 7, F(ab')2 at day 2, or Fab at day 1, respectively. Because the radioactivity remaining in the tumor with Fab was low, the image was insufficient. Throughout the period, less than 10% of the control IgG and its fragments remained in the tumor. Microautoradiography confirmed the binding of MAb 15 and its fragments to the tumor cells. In this study the F(ab')2 was the best compromise between the slowly cleared IgG and the poorly localized Fab in tumor imaging. 相似文献
12.
Kazuma Ogawa Kazuhiro Shiba Nasima Akhter Mitsuyoshi Yoshimoto Kohshin Washiyama Seigo Kinuya Keiichi Kawai Hirofumi Mori 《Cancer science》2009,100(11):2188-2192
It has been reported that sigma receptors are highly expressed in a variety of human tumors. In this study, we selected (+)-2-[4-(4-iodophenyl)piperidino] cyclohexanol [(+)- p IV] as a sigma receptor ligand and evaluated the potential of radioiodinated (+)- p IV for tumor imaging and therapy. (+)-[125/131 I] p IV was prepared by an iododestannylation reaction under no-carrier-added conditions with radiochemical purity over 99% after HPLC purification. Biodistribution experiments were performed by the intravenous injection of (+)-[125 I] p IV into mice bearing human prostate tumors (DU-145). Blocking studies were performed by intravenous injection of (+)-[125 I] p IV mixed with an excess amount of unlabeled sigma ligand into DU-145 tumor-bearing mice. For therapeutic study, (+)-[131 I] p IV was injected at a dose of 7.4 MBq followed by measurement of the tumor size. In biodistribution experiments, (+)-[125 I] p IV showed high uptake and long residence in the tumor. High tumor to blood and muscle ratios were achieved because the radioactivity levels of blood and muscle were low. However, the accumulations of radioactivity in non-target tissues, such as liver and kidney, were high. The radioactivity in the non-target tissues slowly decreased over time. Co-injection of (+)-[125 I] p IV with an excess amount of unlabeled sigma ligand resulted in a significant decrease in the tumor/blood ratio, indicating sigma receptor-mediated tumor uptake. In therapeutic study, tumor growth in mice treated with (+)-[131 I] p IV was significantly inhibited compared to that of an untreated group. These results indicate that radioiodinated (+)- p IV has a high potential for sigma receptor imaging in tumor and radionuclide receptor therapy. ( Cancer Sci 2009) 相似文献
13.
Localization of Small-cell Lung Cancer Xenografts with Iodine-125-, Indium-111-, and Rhenium-188-Somatostatin Analogs 总被引:2,自引:0,他引:2
Makoto Hosono Masako N. Hosono Thomas Haberberger Paul O. Zamora Stefan Guhlke Hans Bender F. F. Russ Knapp Hans J. Biersack 《Cancer science》1996,87(9):995-1000
We examined the potential of radiolabeled somatostatin analogs, 125 I-Tyr-3-octreotide (125 I-octreotide), 111 In-DTPA(diethylenetriaminepentaacetatic acid)- d -Phe-1-octreotide (111 In-octreotide), and 188 Re-octreotide for targeting small-cell lung cancer (SCLC) in a mouse model. Tyr-3-octreotide was labeled with 125 I by the chloramine T method, and 111 In-octreotide was obtained as a kit, while 188 Re was eluted from a 188 W/188 Re generator, and octreotide was directly labeled with 188 Re by reducing disulfide bonds. The 125 I-, 111 In-, and 188 Re-octreotides were injected i.v. into athymic mice bearing NCI-H69 tumors, and the biodistributions were determined at 15 min, and 2, 4, 8, and 24 h. Tumor uptakes were 0.5±0.2, 0.3±0.1, 0.3±0.1 %ID/g, and tumor-to-blood ratios were 1.8, 11.9, 1.2 at 8 h for 125 I-, 111 In-, and 188 Re-octreotides, respectively. Accumulations of 111 In-octreotide in normal tissues were lower than those of 125 I- and 188 Re-octreotides. 188 Re-octreotide can be used to localize SCLC lesions as efficiently as radioiodinated octreotide. However, 111 In-octreotide was the most suitable agent to obtain high tumor-to-normal tissue contrast for localizing SCLC. 相似文献
14.
Tsuneo Saga Isamu Ishiwata Keigo Endo Harumi Sakahara Mitsuru Koizumi Yuji Watanabe Toshiharu Nakai Makoto Hosono Hiroshi Ishikawa Masumi Sawada Junji Konishi 《Cancer science》1990,81(11):1141-1148
By immunizing a mouse with HOUA-1 cells established from an endometrial cancer patient, two murine monoclonal antibodies designated 196–14 and 196–28 were generated, which were reactive with ovarian cancer-associated antigen CA125, originally defined by OC125 antibody. Antigenic determinants of these antibodies, although overlapping each other, were different from that of OC125 and the combined use of 125 I-labeled 196–14 and OC125-coated beads markedly increased the sensitivity of measuring CA125 antigen. Both radioiodinated and 111 In-labeled 196–14 localized well in CA125-producing human ovarian cancer tissues OVA-5 xenografted in nude mice. The biodistribution of radioiodinated 196–14 was quite different from that of 111 In-labeled 196–14. Radioiodine was cleared faster from the OVA-5 tumor, making a clear contrast to the prolonged retention of 111 In in the tumor. Initial tumor uptake of radioiodinated 196–14 was the same as that of 111 In-labeled 196–14 but decreased thereafter, due to the dehalogenation of radioiodinated antibody in the tumor. This antibody-tumor model seems to be suitable for examining the usefulness of monoclonal antibody-conjugates in the diagnosis and therapy of CA125-producing endometrial or ovarian cancers. 相似文献
15.
Kazuya Kitamura Toshio Takahashi Takuya Miyagaki Nobuki Yamaoka Hiroshi Tsurumi Eigo Ohtsuji Michiko Kamiguchi Akinori Noguchi Toshiharu Yamaguchi 《Cancer science》1992,83(7):769-774
The murine monoclonal antibody (Mab) A7 conjugated to neocarzinostatin (A7-NCS) was injected intratumorally (IT) into tumor bearing nude mice. Its pharmacokinetics and tumoricidal effects were compared in the high, moderate and low antigen expressing xenograft for SW1116, WiDr and KB tumor-bearing nude mice, respectively. When injected IT into nude mice, [125 I]A7-NCS was retained in the tumors according to the degree of antigen expression; it was also disseminated into the blood inverse proportion to the antigen expression. Addition of an excess amount of Mab A7 reduced [125 I]-A7-NCS accumulation in SW1116 xenograft and elevated the [125 I]A7-NCS concentration in the circulation. Complete tumor reduction was found in all 5 mice with SW1116 tumor, and 2 of 5 mice with WiDr tumor. However, only incomplete tumor suppression was observed in mice with the KB tumor. The significant tumor reduction in SW1116 bearing nude mice was attenuated when excess of Mab A7 was simultaneously administered with A7-NCS- These findings indicate that A7-NCS was localized in the target tumors and exerted its tumoricidal effects depending on the degree of antigen-antibody interaction when administered IT. Thus, A7-NCS can be used successfully in vivo for local therapy, auguring new and promising applications for local cancer therapy. 相似文献
16.
Tsuneo Saga Harumi Sakahara Yuji Nakamoto Noriko Sato Songji Zhao Yasuhiko Iida Masahide Kuroki Keigo Endo Junji Konishi 《Cancer science》1999,90(3):342-348
The pharmacokinetics of a therapeutic dose of 131 I-labeled antibody and the absorbed dose in liver micrometastases of human colon cancer LS174T in female BALB/c nu / nu mice were investigated, along with the long-term therapeutic effect. Mice with liver micrometastases were given an intravenous injection of 131 I-labeled anti-carcinoembryonic antigen (CEA) antibody F33-104 (8.88 MBq/40 μg). The biodistribution of the antibody was determined 1, 2, 4, 6, and 10 days later. The absorbed dose was estimated for three hypothetical tumor diameters; 1,000, 500, and 300 μm. Autoradiography showed a homogeneous distribution of radioactivity in the micrometastases, and a high uptake was maintained until day 6 (24.0 % injected dose (ID)/g on day 1 to 17.8 %ID/g on day 6), but decreased thereafter. The absorbed doses in the 1,000-, 500-, and 300-μm tumors were calculated to be 19.1, 12.0, and 8.2 Gy, respectively. The intravenous injection of the 131 I-labeled antibody also showed a dose-dependent therapeutic effect (all mice of the nontreated group died, with a mean survival period of 4 weeks; 3 of the 8 mice that received 9.25 MBq survived up to 120 days with no sign of liver metastasis). These data give further evidence that micrometastasis is a good target of radioimmunotherapy, and that an absorbed dose of less than 20 Gy can effectively control small metastatic lesions. 相似文献
17.
Junichi Sakamoto Tomoyuki Kato Tadashi Watanabe Hiroki Murayama Kimio Wada Tsuyoshi Sato Hiroshi Takagi Kunio Kondo Fumio Sasaki Choichiro Kido Hiroaki Nakazato Ryuzo Ueda Toshitada Takahashi 《Cancer science》1992,83(12):1373-1381
H-15 (HT-29-15) is an IgG1 mouse monoclonal antibody (mAb) to a cell surface antigen (molecular mass, 200,000 daltons) present on virtually all colorectal cancers and also in normal pancreatic ducts and bile ducts, but not in other normal tissues. The biological distribution and imaging characteristics of iodine-131 (l31 I)-labeled mAb H-15 were studied in 5 primary colorectal cancer patients and 9 patients with local recurrence of colorectal cancer. H-15 mAb labeled with 0.5-10 mCi of 131 I was administered 7 to 8 days before surgery at 4 dose levels, ranging from 0.2 to 6 nig. Selective mAb H-15 localization to tumor tissues was demonstrated in 6 of 12 patients with antigen-positive tumors: in two patients, recurrent tumors were negative to H-15 mAb, although the primary tumors were positive. In six patients with positive radioimaging, tumor:normal tissue ratios ranged from 2.05 to 5.35 and tumor:serum ratios from 1,18 to 2.73. The clarity of images seems to correlate well with the latter ratios. Technetium-99 (99m Tc)-albumin blood pool studies in selected cases showed that local recurrence of colorectal cancers was hypovascular, emphasizing the selective localization of mAb H-15 despite poor blood flow distribution in the tumors. The results altogether demonstrated that radioimmnnodetection with 131 I mAb H-15 is valuable for differentiating recurrent colorectal cancer from granuloma formation after surgery. 相似文献
18.
Harumasa Ohyanagi Hidefumi Ishida Tsuneyuki Ishida Nobuhiko Soyama Masahiro Yamamoto Shuichi Okumura Yoshiaki Kano Yasuo Ueda Yoichi Saitoh 《Cancer science》1988,79(12):1349-1358
A monoclonal antibody, KM10 (IgG1 ) was produced by fusing spleen cells from a human gastric cancer cell (MKN45)-primed BALB/c mouse with the murine myeloma cell line X63-Ag8-653. The antibody reacted strongly with the plasma membrane of human gastrointestinal carcinoma. Sections of the malignant and benign tissues were tested with immunoperoxidase. All of 10 (100%) large intestinal cancers, 26 of 31 (84%) gastric cancers, 5 of 7 (71%) pancreatic cancers and all of 3 (100%) ampullary cancers reacted positively. Moderate or weak reactivity was observed with normal human tissues, hepatoma and carcinomas of mammary, thyroid and adrenal glands. According to a study of the distribution of 125 I-labeled KM10 in nude mice bearing human gastric cancer, KM10 selectively localized in tumor tissue rather than normal tissue. Whole body autoradiography also supported such a selective distribution. Destruction of antigenic properties by pronase digestion demonstrated its protein nature and by Western blot analysis, it was identified as a protein with an Mr of 180–200 kd. KM10-adriamycin (ADM) conjugate was prepared via an oxidized dextran bridge and this immunoconjugate retained the binding activity against human gastric cancer. MKN45 cells were inoculated subcutaneously into athymic mice and intravenous treatment was begun when the tumor became measurable. A dose-dependent antitnmor activity was observed in vivo with KM10-ADM conjugate, while this conjugate was less toxic than free ADM. 相似文献
19.
Radioimmunodetection of human glioma xenografts by monoclonal antibody to epidermal growth factor receptor 总被引:2,自引:0,他引:2
H Takahashi D Herlyn B Atkinson J Powe U Rodeck A Alavi D A Bruce H Koprowski 《Cancer research》1987,47(14):3847-3850
Murine IgG2a monoclonal antibody (MAb) 425 specifically detects epidermal growth factor receptor, which is expressed on human gliomas and tumors of other tissue origin but rarely on normal brain tissues, and not at all on bone marrow and peripheral blood cells. 131I-labeled F(ab')2 fragments of this MAb injected into nude mice grafted with U-87 MG glioma cells preferentially localized in tumor tissue compared to normal mouse tissues, as determined by differential tissue counting of radioactivity. The mean tumor-to-tissue ratios of radioactivity ranged between 8.2 (blood) and 55.8 (muscle) at 2 days after the injection of 15 muCi of 131I-425 F(ab')2/mouse. Radiolabeled fragments of an anti-hepatitis virus IgG2a MAb did not localize in tumors. The localization index derived from the ratios of specific antibody to indifferent antibody in tumor tissue relative to blood was 9.94 at 2 days following the MAb injection. The labeled MAb did not localize in a xenograft of colorectal cancer tumor, which does not express the epidermal growth factor receptor. Tumors could be located by whole-body gamma-scintigraphy without background subtraction following the injection of 100 muCi of radiolabeled MAb 425 F(ab')2 fragments. The data suggest that MAb 425 is a likely candidate for clinical diagnostic and radioimmunotherapy trials. 相似文献
20.
Noriko Sato Tsuneo Saga Harumi Sakahara Yuji Nakamoto Songji Zhao Masahide Kuroki Yasuhiko Iida Keigo Endo Junji Konishi 《Cancer science》2000,91(6):622-628
Myelotoxicity is the main factor which decides the maximum tolerated dose (MTD) in radioimmunotherapy (RIT). Since bone marrow is mostly irradiated from blood radioactivity, enhancing the clearance of unbound circulating radiolabeled antibody is important to reduce myelotoxicity and to increase the MTD. We applied the avidin chase method, which was devised to obtain high tumorto-background ratios in tumor-targeting, to RIT of experimental liver micrometastases and evaluated its influence on the side effects and therapeutic outcome. Seven days after intrasplenic injection of human colon cancer LS174T cells, nude mice were intravenously injected with biotinylated 131 I-labeled anti-CEA monoclonal antibody (MAb) (24–38 μg, 11.1 MBq). Mice of the chase group then received an intravenous injection of avidin twice (24 and 30 h, 72–115 μg each). Biodistribution, side effects (white blood cell counts and body weight change), and short- and long-term therapeutic effects were determined. Avidin chase markedly accelerated the clearance of radiolabeled MAb from the blood ( P < 0.0001) and normal tissues, resulting in milder leukocytopenia and body weight loss, both of which recovered earlier than in the non-chase group ( P < 0.01). The tumor uptake of radiolabeled MAb was also decreased by avidin chase, but the metastases-to-background ratios were increased. Avidin chase gave the therapeutic gain ratio of 1.89. Treated groups with and without avidin chase showed significant therapeutic effects compared to the non-treated group. There was no significant difference in the therapeutic effects between the two treated groups. Avidin chase effectively reduced the side effects of RIT and should increase the MTD. 相似文献