共查询到20条相似文献,搜索用时 15 毫秒
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K Endo 《Nihon Igaku Hōshasen Gakkai zasshi. Nippon acta radiologica》1990,50(8):901-909
Monoclonal antibodies (MoAbs) are expected to carry radionuclides selectively to target tissues and to offer antigen-specific diagnosis. Indium (In)-111 has many favorable nuclear properties and is efficiently labeled with MoAbs using DTPA as a bifunctional chelating agent. In-111 labeled MoAbs are clinically employed for the diagnosis of malignant melanoma, colorectal cancer and acute myocardial infarction in Japan. Although non-specific deposit of In-111 was seen in liver and bone-marrow, scintigraphy using In-111 labeled MoAbs was encouraging, since it detected about 80% of tumors, tumors missed by conventional diagnostic methods such as CT, and tumors in patients with normal serum CEA values, and acute myocarditis as well as acute myocardial infarction was positive with In-11 labeled Fab fraction of anti-myosin Ab. Acute or subacute toxicity was not observed. Human anti-murine antibody (HAMA) was detected in 53 of 64 (82.8%) patients who were intravenously administered with 20 to 42 mg of anti-melanoma or anti-CEA MoAbs (whole IgG). In contrast, only 5 of 406 (1.2%) patients had detectable levels of HAMA in their serum after receiving 0.5 mg of Fab fraction of MoAb. Recently mouse-human chimeric Ab has been produced by recombinant DNA techniques, which localized well in xenografted tumors and seems to be promising for clinical use. Investigations are under way to increase the tumor to non-tumor ratio by modifying chelating agents for coupling MoAbs with radionuclides. 相似文献
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Chizuru Sogawa Atsushi B. Tsuji Hitomi Sudo Aya Sugyo Chisato Yoshida Kenichi Odaka Tomoya Uehara Yasushi Arano Mitsuru Koizumi Tsuneo Saga 《Nuclear medicine and biology》2010,37(2):179-187
IntroductionGastrointestinal stromal tumor (GIST) is the most common mesenchymal tumor arising from the gastrointestinal tract and highly expresses mutated c-kit. We aimed to develop a specific and sensitive method for detecting GISTs using radiolabeled anti-c-kit monoclonal antibody.MethodsA mutated c-kit-expressing cell clone was established by transfecting an expressing vector of mutated c-kit gene into HEK293 human embryonic kidney cells. The tumors were developed by inoculating c-kit-expressing cells into nude mice. 125I- and 111In-labeled anti-c-kit antibodies (12A8 and 41A11) were evaluated in vitro by cell binding, competitive inhibition and cellular internalization assays, and in vivo by biodistribution and imaging studies in tumor-bearing mice.ResultsBoth 125I- and 111In-labeled antibodies showed specific binding with c-kit-expressing cells with high affinity (dissociation constants = 2.2–7.1×109 M?1). Internalization assay showed that 125I-labeled antibodies were rapidly internalized and dehalogenated, with the release of 125I from the cells, resulting in reduction of cell-associated radioactivity with time. In contrast, 111In-labeled antibody was internalized but did not result in the reduced radioactivity associated with tumor cells. Reflecting this phenomenon, the in vivo tumor uptake of 125I-labeled antibody was low on Day 1, further decreasing with time, while tumor uptake of 111In-labeled antibody was high on Day 1, further increasing with time. The xenografted tumor was clearly visualized by scintigraphy after injection of 111In-labeled antibody.ConclusionThe anti-c-kit monoclonal antibody labeled with a metal radionuclide would be promising for c-kit-targeted imaging of GISTs. 相似文献
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Improved radiolabeled monoclonal antibody uptake by lavage of intraperitoneal carcinomatosis in mice
The effect of peritoneal lavage with saline on tumor and systemic uptake of intraperitoneally administered tumor-specific (131I-5G6.4) and nonspecific (125I-UPC-10) radiolabeled monoclonal antibodies was evaluated in a nude mouse model of human intraperitoneal ovarian carcinomatosis (IP3 model). Peritoneal lavage at 2 or 6 hr postintraperitoneal antibody injection significantly improves intraperitoneal tumor/nontumor uptake ratios of specific antibody apparently by limiting systemic exposure to antibody. This enhancement tends to be more dramatic if lavage is performed within 2 hr, rather than 6 hr, of intraperitoneal antibody administration, though both times result in significant improvements in target/background ratios over no lavage. Twenty-four-hour tumor/nontumor ratios for specific antibody 5G6.4 generally are 1.5-fourfold higher following lavage than those achieved in control animals, without decreasing absolute tumor uptake of specific radiolabeled antibody. By contrast, nonspecific antibody UPC-10 binding is lower in tumor and normal tissues following lavage, with no lavage-induced improvement in tumor/nontumor ratios seen. Peritoneal lavage is a simple method to allow for specific antibody binding to accessible intraperitoneal tumors yet to limit systemic exposure thus increasing the therapeutic margin. This method may have considerable applicability in the enhancement of intraperitoneal immunoconjugate delivery to intraperitoneal tumors. 相似文献
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Use of specific antibody for rapid clearance of circulating blood background from radiolabeled tumor imaging proteins 总被引:1,自引:0,他引:1
Goodwin David Meares Claude Diamanti Carol McCall Michael Lai Corazon Torti Frank McTigue Maureen Martin Brian 《European journal of nuclear medicine and molecular imaging》1984,9(5):209-215
A major problem that arises when radiolabeled serum proteins are used for tumor imaging is the presence of a large amount of circulating background activity that persists for several days. This delays imaging for at least 2 days following injection and necessitates computer subtraction of simulated background (second radiopharmaceutical injection) which introduces artifacts that are difficult to control. We propose here the injection of specific antibody immediately before imaging as an alternate way of reducing blood background through clearance of the immune complex by the liver.
111In-alkyl human transferrin and IgG were injected IV in BALB/c tumor mice, and followed in 18 h by anti-human transferrin and anti-human IgG antibody IV. Two hours later, the tumor and organ distribution of activity was compared with control mice not receiving antibody. 111In-transferrin blood activity was reduced to 1/48 of control with no decrease in tumor concentration: as a result, the tumor to blood ratio increased from 1.4:1 to 78:1. 111In-IgG blood activity was reduced to 1/17 of control, again with no decrease in tumor. The tumor to blood ratios increased from 0.7:1 to 17:1. The liver picked up most of the blood activity with none of the complex going to spleen, bone marrow, or kidney. Dog experiments showed clearance of blood was 90% complete in less than 15 min following antibody injection. Simultaneous scintillation images showed complete clearance of activity from the heart and great vessels in the chest and neck, and over the abdomen, with a concomitant increase in liver activity but no increase in spleen, kidney, or bone marrow activity. These studies show the feasibility of using specific antibody to lower the blood background just minutes prior to tumor imaging procedures using radiolabeled proteins.These studies were supported in part by a Veterans Administration Research Grant, and PHS Grant Number 5 ROI CA 28343 (D Goodwin), and CA 16861, RCDA CA 00462 (C Meares) 相似文献
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Use of specific antibody for rapid clearance of circulating blood background from radiolabeled tumor imaging proteins 总被引:1,自引:0,他引:1
D Goodwin C Meares C Diamanti M McCall C Lai F Torti M McTigue B Martin 《European journal of nuclear medicine》1984,9(5):209-215
A major problem that arises when radiolabeled serum proteins are used for tumor imaging is the presence of a large amount of circulating background activity that persists for several days. This delays imaging for at least 2 days following injection and necessitates computer subtraction of simulated background (second radiopharmaceutical injection) which introduces artifacts that are difficult to control. We propose here the injection of specific antibody immediately before imaging as an alternate way of reducing blood background through clearance of the immune complex by the liver. 111In-alkyl human transferrin and IgG were injected IV in BALB/c tumor mice, and followed in 18 h by anti-human transferrin and anti-human IgG antibody IV. Two hours later, the tumor and organ distribution of activity was compared with control mice not receiving antibody. 111In-transferrin blood activity was reduced to 1/48 of control with no decrease in tumor concentration: as a result, the tumor to blood ratio increased from 1.4:1 to 78:1. 111In-IgG blood activity was reduced to 1/17 of control, again with no decrease in tumor. The tumor to blood ratios increased from 0.7:1 to 17:1. The liver picked up most of the blood activity with none of the complex going to spleen, bone marrow, or kidney. Dog experiments showed clearance of blood was 90% complete in less than 15 min following antibody injection. Simultaneous scintillation images showed complete clearance of activity from the heart and great vessels in the chest and neck, and over the abdomen, with a concomitant increase in liver activity but no increase in spleen, kidney, or bone marrow activity.(ABSTRACT TRUNCATED AT 250 WORDS) 相似文献
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Improved renal clearance and tumor targeting of 99mTc-labeled anti-Tac monoclonal antibody Fab by chemical modifications 总被引:1,自引:0,他引:1
Kim MK Jeong HJ Kao CH Yao Z Paik DS Pie JE Kobayashi H Waldmann TA Carrasquillo JA Paik CH 《Nuclear medicine and biology》2002,29(2):139-146
This study was undertaken to improve the renal clearance and tumor targeting properties of 99mTc-labeled humanized anti-Tac (HuTac) monoclonal antibody Fab fragments using two chemical approaches: 1) labeling with a renal secretion agent 99mTc-mercaptoacetyltriglycine (MAG3) and 2) lowering its isoelectric point (pI) by acylation. HuTac Fab (3.3 mg/mL) was reacted with a trifluorophenyl ester (TFP) of 99mTc-MAG3 alone or was additionally reacted with TFP-glycolate to reduce the pI. In Balb/c mice, 99mTc-MAG3-Fab (pI > 9.3) rapidly accumulated in the kidneys (177% injected dose [ID]/g at 15 min) and then gradually cleared out of the kidneys. In contrast, the glycolation (pI 4.6 approximately 6.6) drastically reduced the renal uptake (31% ID/g) and also the whole-body retention (82% ID vs 101% for the nonglycolated) at 15 min, indicating that the glycolated 99mTc-MAG3-Fab (pI 4.6 approximately 6.6) was rapidly excreted. The glycolated remained in the blood longer than the nonglycolated (1.2% vs 0.3% ID/g at 360 min), but this effect was less drastic than the effect shown on the renal uptake. In nude mice bearing receptor-positive (ATAC4) tumors, the glycolated 99mTc-MAG3-Fab increased the peak tumor uptake to 14.8% ID/g from 8.3% ID/g for 99mTc-MAG3-Fab, whereas the glycolation resulted in a drastic reduction of the renal uptake at 15 min. We demonstrated that the renal clearance and the tumor targeting of Fab could be optimized by chemical modifications. 相似文献
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Blood clearance of radiolabeled antibody: enhancement by lactosamination and treatment with biotin-avidin or anti-mouse IgG antibodies 总被引:1,自引:0,他引:1
A L Klibanov A V Martynov M A Slinkin M D Sakharov IYuSmirnov V R Muzykantov S M Danilov V P Torchilin 《Journal of nuclear medicine》1988,29(12):1951-1956
Methods of rapid blood clearance of 111In-labeled mouse monoclonal antibody 9B9 against angiotensin-converting enzyme were studied. Indium-111-9B9 is specifically accumulated in rat lung, but its blood clearance is relatively slow and target-to-blood radioactivity ratio/g tissue (localization ratio) increases from 11 to 30 only 48 hr postinjection. Injection of second (anti-mouse immunoglobulin) antibodies results in slight (1.8-fold) increase of 9B9 localization ratio. Chemical modification of 9B9 aminogroups with lactose results in enhanced liver uptake and rapid blood clearance of antibody. Blood radioactivity level decreases tenfold, and as a result localization ratio increases threefold (up to 38 in 30 min). Injection of avidin following the injection of biotinylated 9B9 results in rapid clearance of blood radioactivity with increased uptake in liver and spleen. Lung uptake is not changed. Localization ratio increases fivefold over the avidin-untreated animal value. Implications of these approaches for various applications in immunoimaging are discussed. 相似文献
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Inhibition of autoradiolysis of radiolabeled monoclonal antibodies by cryopreservation 总被引:2,自引:0,他引:2
Autoradiolysis of therapeutic doses of monoclonal antibodies can occur rapidly, limits their shelf life and makes onsite radiolabeling a near-necessity. We evaluated freezing of three different 131I-labeled murine monoclonal antibodies at -70 degrees C, immediately following radiolabeling, as a method of diminishing autoradiolysis, and of preserving immunoreactivity. Freezing greatly limits the ability of radiation-induced free radicals to diffuse in solution and thus produce radiolytic damage. By freezing at -70 degrees C autoradiolytic damage of immunoreactivity of three different 131I monoclonal antibodies could be largely eliminated, in contrast to the 80-90% losses in immunoreactivity seen with storage at 4 degrees C for a period of 1 to 12 days. Reduced in vitro deiodination rates are also seen for frozen antibodies. Limited studies with 125I-labeled antibodies indicate autoradiolysis does occur, though at a slower rate per mCi than for 131I, and that this process is also retarded by freezing. Freezing may be valuable while quality control procedures are performed following radiolabeling as well as if temporary storage or shipment of radioantibodies prior to patient dosing is undertaken. While the approach should be validated for each antibody studied, freezing of therapeutic doses of monoclonal antibodies appears to be a simple and effective approach to the problem of autoradiolysis. 相似文献
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Methods for the study of the metabolism of radiolabeled monoclonal antibodies by liver and tumor 总被引:3,自引:0,他引:3
Methods for elucidating the mechanisms by which radiolabeled antibodies are taken up and accumulated in tumor and liver are reviewed. These include the use of isolated perfused rat livers, RES blockade using dextran sulfate, single and double labeled antibodies, micropore chambers for the accumulation of the interstitial fluid, and in vitro tissue culture studies of antibody metabolism. Each method has its utility, examples of which will be discussed along with the methods' limitations. All of the methods have value in furthering our understanding of the metabolism of monoclonal antibodies both in vivo and in vitro. Use of these procedures to create a greater understanding of radiolabeled antibody metabolism, hopefully, will result in improved clinically useful agents for diagnosis and therapy. 相似文献
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Molecular targeting therapy has become a relevant therapeutic strategy for cancer. There are several monoclonal antibodies used for the treatment of malignant tumors. Radioimmunoconjugate is composed of antibody and radionuclide showing a synergistic effect of radiation and immunemediated cellular toxicity and thereby enabling increased efficacy and minimizing toxicity. Radioimmunotherapy using 131I- and 90Y-labeled anti-CD20 monoclonal antibodies is now indicated for the treatment of patients with CD20 antigen-expressing relapsed or refractory, low-grade or transformed non-Hodgkin's lymphoma (NHL), including patients who are refractory to anti-CD20 monoclonal antibody (rituximab) therapy in the United States. It has been exhibiting favorable anti-tumor efficacy in patients with NHL as compared with rituximab. Myelosuppression is the main side effect associated with the radioimmunotherapy but is usually reversible, and nonhematologic adverse reactions are mild to moderate. Following the impressive results of therapy using radiolabeled monoclonal antibodies for NHL, radioimmunotherapy for solid tumors has been examined; however, the results were unfavorable and did warrant further clinical trials as a single agent. Future studies on radioimmunotherapy for solid tumors should focus on the new strategies of targeting such as locoregional administration for intraperitoneal dissemination, and combination therapy with chemotherapy or cytostatic therapy. Although radioimmunotherapy for NHL has shown excellent results comparable to aggressive chemotherapy without severe adverse effects, additional clinical trials should be performed to define the proper role of radioimmunoconjugates as a relevant strategy for cure of NHL. 相似文献
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Miraldi FD; Nelson AD; Kraly C; Ellery S; Landmeier B; Coccia PF; Strandjord SE; Cheung NK 《Radiology》1986,161(2):413-418
In a previous study, the authors showed that iodine-131 labeled monoclonal antibody (Mab 3F8) could be used to image human neuroblastoma xenografts in mice with excellent tumor-to-tissue ratios. In this study they report their experience with six patients scanned with radiolabeled 3F8. There was strong accumulation of the labeled antibody in viable tumor, but no significant uptake was noted in normal brain, liver, spleen, or adrenal glands. Tumor-to-nontumor activity ratios varied but were approximately 10:1-20:1. This ratio yields good contrast for visualization. Time-activity curves show that radioactivity levels in normal tissue have a half-time of about 40 hours, whereas tumor tissues show a half-time of about 60 hours. Significant gastric secretion of free iodine demonstrated that the Mab was being deiodinated. Calculated radiation doses indicate that tumors receive at least ten times the dose to other tissues. The results indicate that Mab 3F8 has clinical potential for both imaging and therapy of human neuroblastomas. 相似文献
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Specific and nonspecific imaging of localized Fisher immunotype 1 Pseudomonas aeruginosa infection with radiolabeled monoclonal antibody 总被引:1,自引:0,他引:1
R H Rubin L S Young W P Hansen M Nedelman R Wilkinson M J Nelles R Callahan B A Khaw H W Strauss 《Journal of nuclear medicine》1988,29(5):651-656
To determine if radiolabeled specific antibodies directed against bacterial antigens could be used to detect sites of infection, gamma camera imaging studies were performed in animals infected with Pseudomonas aeruginosa. Murine monoclonal antibodies (Mabs) directed against Fisher Immunotype 1 Pseudomonas aeruginosa and a nonmicrobial, nonmammalian haptene, p-arsanilic acid, were labeled with 125I by the lodogen-Bead method. Unilateral, deep thigh infections were created by innoculation with 2 X 10(8) Fisher Immunotype 1 P. aeruginosa. Twenty-four hours later, one of the radiolabeled antibodies was injected intravenously at a dose of 0.25 mg/kg (100-150 microCi). Serial gamma imaging was then carried out beginning at 4 hr and at approximately 24-hr intervals thereafter. Beginning as early as 4 hr postinjection, the area of inflammation could be visualized with either the specific or nonspecific Mab, with the images continuing to intensify until 24-48 hr postinjection. At 48 hr, the contrast between lesion and background with the nonspecific Mab began to fade, while the contrast in the specific Mab-generated images continued to intensify until approximately 192 hr postinjection. Clear-cut differentiation between specific and nonspecific Mab-generated images was possible by 72 hr postinjection. We conclude that specific immune imaging of localized infection with Mab's directed against specific microbial antigens is possible and should be clinically useful. In addition, images created by the localization of immunoglobulin non-specifically at the site of inflammation in the first 24-48 hr postinjection may also provide useful information as to the anatomic location of hidden abscesses. 相似文献
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Tumor imaging with monoclonal antibodies 总被引:1,自引:0,他引:1
D M Goldenberg 《Journal of nuclear medicine》1983,24(4):360-362
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J Malamitsi D Skarlos S Fotiou P Papakostas G Aravantinos D Vassilarou J Taylor-Papadimitriou K Koutoulidis G Hooker D Snook 《Journal of nuclear medicine》1988,29(12):1910-1915
Six patients with metastatic breast cancer and malignant pleural effusions and 13 patients with known or suspected ovarian cancer, underwent immunoscintigraphy after intracavitary (intrapleural or intraperitoneal) administration of iodine-131-(131I) or indium-111-(111In) labeled tumor associated monoclonal antibodies HMFG2 and H17E2. This method proved to be sensitive and specific with a true-positive result in 13 out of 14 patients with tumor and a true-negative result in five out of five patients without tumor. At any one time, 65%-80% of the whole-body radioactivity was closely associated with the cavity into which the radiolabeled antibody was administered while the radioactivity in the blood was always low, (approximately 4 X 10(-3) of administered dose/ml of blood). Concentrations of radiolabeled antibody (per gram of tumor tissue) ranged from 0.02%-0.1% of the injected dose in intracavitary tumors, but only 0.002% in a retroperitoneal metastasis. The specificity of this approach was documented in four control patients with benign ovarian cysts and in two patients who were imaged using both specific and nonspecific radiolabeled antibody. We conclude that the intracavitary administration of 131I- or 111In-labeled HMFG2 and H17E2 is a favorable route of administration and offers significant advantages over previously reported intravenous administration for the localization of breast or ovarian metastases confined to the pleural or peritoneal cavities. 相似文献
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M Kanke G R Matsueda H W Strauss T Yasuda C S Liau B A Khaw 《Journal of nuclear medicine》1991,32(6):1254-1260
Indium-111-labeled monoclonal antibody 64C5 specific for the beta-chain of fibrin monomer was used to image canine (n = 6) experimental pulmonary emboli (at least one barium-thrombin and one copper-coil induced clot per dog). Uptake of 111In-64C5 and 125I-control-DIG26-11 were compared in 10 clots (7 barium-thrombin and 3 copper-coil) identified in the lungs. There was no difference in the blood clearance of 111In-64C5 and 125I-DIG26-11. Uptake of 111In-64C5 (0.183 +/- 0.105, mean %ID/g) was greater than 125I-DIG26-11 (0.024 +/- 0.025) in pulmonary clots (p less than 0.001). Mean thrombus to blood ratios at 24 hr were 6.78:1 for 64C5 and 0.57:1 for DIG26-11. The clots visualized in vivo were larger (0.315 +/- 0.381 g) than clots not visualized (0.089 +/- 0.098). Negative images were recorded in three dogs with pulmonary emboli, injected with 111In-labeled control monoclonal antibody 3H3. These data suggest that 111In-labeled antifibrin can detect large pulmonary emboli in vivo. 相似文献
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H Sakahara K Endo M Koizumi T Nakashima M Kunimatsu Y Watanabe Y Kawamura T Nakamura H Tanaka Y Kotoura 《Journal of nuclear medicine》1988,29(2):235-240
The relationship between in vitro cell binding and in vivo tumor accumulation of radiolabeled antibodies was studied using 125I- and 111In-labeled monoclonal antibodies to human osteosarcoma, and a human osteosarcoma xenograft (KT005) in nude mice. Three monoclonal antibodies--OST6, OST7, and OST15--raised against human osteosarcoma recognize the same antigen molecule. Although the binding of both 125I- and 111In-labeled OST6 to KT005 cells was higher than that of radiolabeled OST7 in vitro, 125I-labeled OST6 showed a faster clearance from the circulation and a lower accumulation in the transplanted tumor than 125I-labeled OST7. In contrast to the radioiodinated antibodies, the in vivo tumor accumulation of 111In-labeled OST6 was higher, although not significantly, than that of 111In-labeled OST7. OST15 showed the lowest binding in vitro, and its in vivo tumor localization was also lower than the others. The discrepancy in tumor uptake between OST6 and OST7 labeled with either 125I or 111In may have been a result of differing blood clearance. These results suggest that binding studies can be used to exclude from in vivo use those antibodies which show very poor binding in vitro, while in vivo serum clearance may be a better test for choosing antibodies with similar binding. 相似文献