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1.
《International journal of radiation applications and instrumentation. Part B, Nuclear medicine and biology》1989,16(8):839-845
Indium-111-labeled antibodies, though providing superior photon flux to iodine-labeled antibodies, can exhibit high levels of accumulation in some non-target organs. In an effort to understand the nature of this non-target uptake we have evaluated the molecular weight of 111In species retained in several tissues by radio-FPLC (sizing chromatography) following injection of [111In]DTPA 5G6.4, a murine monoclonal antibody, into normal mice. Blood, liver and kidneys were removed, and liver and kidneys were homogenized at several time points after antibody injection. The proportion of 111In-containing species was found to vary with the tissue and with time. Analysis of blood showed only radiolabeled antibody. In the liver, several 111In species were identified with molecular weights compatible with intact antibody, [111In]transferrin, and low molecular weight complexes, with an increase in the proportion of [111In]transferrin and low molecular weight species occurring over time. While the same molecular weight species were also identified in the kidneys, the kidneys contained the largest percentage of low molecular weight species which increased over time. When 125I-labeled 5G6.4 was injected and the tissues similarly analyzed, only radioactive material with the molecular weight of intact antibody was detected. Comparison of two methods of purification of [111In]labeled antibody after labeling revealed a significant difference in the organ uptake of radiolabeled products for 111In. Although dialysis was sufficient for the removal of labile 111In, as determined by TLC, subsequent sizing chromatography on Bio-Gel P-60 dramatically dropped the hepatic and renal uptake of 111In relative to blood and diminished the proportion of the low molecular weight species present on sizing FPLC of extracts from tissues. These data indicate that low and intermediate molecular weight 111In compounds are accreted in the liver and kidneys following the i.p. injection of 111In-labeled monoclonal antibodies and that their uptake can be diminished by more stringent radioantibody purification. This knowledge may be valuable in developing methods for reducing non-target 111In uptake. 相似文献
2.
Malcolm V. Pimm Nicholas C. Armitage Alan C. Perkins William Smith Robert W. Baldwin 《Cancer immunology, immunotherapy : CII》1985,19(1):8-17
Summary A mouse monoclonal anti-CEA antibody (11.285.14) has been examined for tumour localization potential by assessing its distribution in immunodeprived mice with xenografts of human colon carcinoma cell lines HCT-8, HRT-18, HT-29, and LS174T and a xenograft (HRVB) established from a primary rectal carcinoma. With four carcinomas (HCT-8, HT-29, LS174T, and HRVB) preferential tumour localization of 125I anti-CEA was seen. Compared with 131I normal IgG1 localization indices of up to 4.4:1 were achieved. Up to 10% of the injected dose of 125I anti-CEA was present/g of tumour tissue and with the largest xenografts examined (3–4 g) up to 40% of the total body reactivity was localized in tumour tissue. The tumour localization of 131I labelled antibody was visualized by external gamma camera imaging. Overall antibody localization correlated with the CEA content of the xenografts and the fourth colon carcinoma xenograft (HRT-18) and an osteogenic sarcoma xenograft (791T), both with very low CEA levels, showed no localization of the monoclonal antibody. 相似文献
3.
Conjugates formed by reaction of monoclonal antibody B72.3 with benzyl isothiocyanate derivatives of four amino polycarboxylate chelators (NTA, EGTA, EDTA, DTPA) were labeled with indium-111 and administered iv to athymic mice bearing antigen-positive (LS174T) and antigen-negative (A375) human tumor xenografts. Conjugate immunoreactivities, antibody dose, and xenograft size were controlled, so that the effects of varying chelate structure could be evaluated under conditions where immunological and physiological factors were effectively held constant. Tissue distribution and excretion of the radiometal at 24 and 48 h postinjection were shown to correlate directly with chelate thermodynamic stability (NTA less than EGTA less than EDTA less than DPTA). Radioactivity levels in the blood and the LS174T xenograft increased, while kidney levels and excretion levels decreased, with increasing chelate stability. The kidney was the only normal organ that accumulated non-antibody-bound 111In, uptake of radioactivity into all other tissues, and in particular the liver, being unaffected by changes in chelate structure. Mean transferrin saturation in the tumor-bearing athymic mice was found to be 65%. It is proposed that uptake of free 111In by serum transferrin is precluded in this model, leading to the observed renal localization of unbound label. Kidney:blood and kidney:LS174T activity ratios at 48 h postinjection provided the most sensitive indices of conjugate instability in vivo, spanning 50- and 20-fold ranges, respectively, between the least stable and the most stable conjugate. It is concluded that this antigen/antibody system and mouse model are well-suited to structure-function studies of immunoglobulin labels. 相似文献
4.
Malcolm V. Pimm Alan C. Perkins Nicholas C. Armitage Robert W. Baldwin 《Cancer immunology, immunotherapy : CII》1985,19(1):18-21
Summary A primary human osteogenic sarcoma was visualized in situ by external gamma-camera imaging following administration of 131I-labelled anti-osteogenic sarcoma monoclonal antibody 791T/36. A xenograft of the tumour established in immunodeprived mice also showed localization of 131I-791T/36 determined by both gamma-camera imaging and organ distribution studies. Radiolabelled normal immunoglobulin showed no tumour localization. Expression of the 791T/36-defined antigen on xenografted tissue was further confirmed by reaction of its in vitro-cultured cells with fluorescein-labelled 791T/36 antibody. 相似文献
5.
《生物化学与生物物理学报:生物膜》1987,901(2):183-190
125I-labeled liposomes, conjugated to an anti-Thy 1.1 monoclonal antibody (MRCOX7), demonstrated up to 7.4-fold greater lymph node uptake than liposomes conjugated to non-specific monoclonal antibody (R-10) after intravenous injection into Thy 1.1 (AKR-J) mice. Uptake of anti-Thy 1.1-conjugated liposomes by the lymph nodes of AKR-J mice was 3-times greater than their uptake by lymph nodes of Thy 1.2 (AKR-Cu) mice. Lymph node localization of anti-Thy 1.1-liposomes was equal to that of control monoclonal antibody-liposomes in Thy 1.2 mice. Conjugation to either monoclonal antibody substantially increased liposome clearance by the liver, while decreasing liposome uptake in a number of organs outside the reticuloendothelial system. Changes in liposome size and phospholipid composition did not significantly alter these results. Administration of a large predose of unconjugated liposomes prior to injection of MRCOX7-conjugated liposomes increased blood levels and reduced liver uptake of the monoclonal antibody-liposome conjugates, but did not further enhance lymph node uptake. This study demonstrates that targeting of liposomes by conjugation to the appropriate monoclonal antibody, can significantly increase their uptake in lymph nodes which contain high levels of cells expressing the target antigen. However, conjugation to monoclonal antibody also increases clearance of liposomes by the liver. To increase the uptake of monoclonal antibody-conjugated liposomes in target tissue, substantial reduction of their clearance by the reticuloendothelial system will be required. 相似文献
6.
Advantage of residualizing radiolabels for an internalizing antibody against the B-cell lymphoma antigen, CD22 总被引:1,自引:0,他引:1
Robert M. Sharkey Thomas M. Behr M. Jules Mattes Rhona Stein Gary L. Griffiths Lisa B. Shih Hans J. Hansen Rosalyn D. Blumenthal Robert M. Dunn Malik E. Juweid D. M. Goldenberg 《Cancer immunology, immunotherapy : CII》1997,44(3):179-188
LL2 is an anti-CD22 pan-B-cell monoclonal antibody which, when radiolabeled, has a high sensitivity for detecting B-cell,
non-Hodgkin’s lymphoma (NHL), as well as an antitumor efficacy in therapeutic applications. The aim of this study was to determine
whether intracellularly retained radiolabels have an advantage in the diagnosis and therapy of lymphoma with LL2. In vitro
studies showed that iodinated LL2 is intracellularly catabolized, with a rapid release of the radioiodine from the cell. In
contrast, residualizing radiolabels, such as radioactive metals, are retained intracellularly for substantially longer. In
vivo studies were performed using LL2-labeled with radioiodine by a non-residualizing (chloramine-T) or a residualizing method
(dilactitol-tyramine, DLT), or with a radioactive metal (111In). The biodistribution of a mixture of 125I (non-residualizing chloramine-T compared to residualizing DLT), 111In-labeled LL2 murine IgG2a or its fragments [F(ab′)2, Fab′], as well as its humanized, CDR-grafted form, was studied in nude mice bearing the RL human B-cell NHL cell line. Radiation
doses were calculated from the biodistribution data according to the Medical International Radiation Dose scheme to assess
the potential advantage for therapeutic applications. At all assay times, tumor uptake was higher with the residualizing labels
(i.e., 111In and DLT-125I) than with the non-residualizing iodine label. For example, tumor/blood ratios of 111In-labeled IgG were 3.2-, 3.5- and 2.8-fold higher than for non-residualizing iodinated IgG on days 3, 7 and 14, respectively.
Similar results were obtained for DLT-labeled IgG and fragments with residualized radiolabels. Tumor/organ ratios also were
higher with residualizing labels. No significant differences in tumor, blood and organ uptake were observed between murine
and humanized LL2. The conventionally iodinated anti-CD20 antibody, 1F5, had tumor uptake values comparable to those of iodinated
LL2, the uptake of both antibodies being strongly dependent on tumor size. These data suggest that, with internalizing antibodies
such as LL2, labeling with intracellularly retained isotopes has an advantage over released ones, which justifies further
clinical trials with residualizing 111In-labeled LL2 for diagnosis, and residualizing 131I and 90Y labels for therapy.
Received: 23 August 1996 / Accepted: 7 February 1997 相似文献
7.
《International journal of radiation applications and instrumentation. Part B, Nuclear medicine and biology》1991,18(5):565-567
Blood exchange transfusions were performed in nude rats with subcutaneous HTB77 human ovarian carcinoma xenografts in an attempt to improve specific monoclonal antibody (MoAb) tumor/non-tumor uptake ratios. Animals were injected intravenously with both 131I-5G6.4 specific and 125I-UPC-10 non-specific MoAb. Twenty-four hours later 65–80% of the original blood was exchanged with normal heparinized rat blood and then these rodents were sacrificed. Exchange transfusion significantly (P < 0.05) decreased normal tissue activities of 131I (except for muscle) by 63–85%. while tumor activity decreased only 5%. Tumor to background ratios increased from 0.1–0.8 to 2.3–6.3. Exchange transfusions substantially enhance tumor/normal tissue antibody uptake ratios and, along with plasmapheresis, may be useful in enhancing antibody localization in vivo, particularly for therapy. 相似文献
8.
Kentaro Fujiwara Keitaro Koyama Kosuke Suga Masako Ikemura Yasutaka Saito Akihiro Hino Hiroko Iwanari Osamu Kusano-Arai Kenichi Mitsui Hiroyuki Kasahara Masashi Fukayama Tatsuhiko Kodama Takao Hamakubo Toshimitsu Momose 《PloS one》2015,10(5)
IntroductionROBO1 is a membrane protein that contributes to tumor metastasis and angiogenesis. We previously reported that 90Y-labeled anti-ROBO1 monoclonal antibody (90Y-anti-ROBO1 IgG) showed an antitumor effect against ROBO1-positive tumors. In this study, we performed a biodistribution study and radioimmunotherapy (RIT) against ROBO1-positive small cell lung cancer (SCLC) models.MethodsFor the biodistribution study, 111In-labeled anti-ROBO1 monoclonal antibody (111In-anti-ROBO1 IgG) was injected into ROBO1-positive SCLC xenograft mice via the tail vein. To evaluate antitumor effects, an RIT study was performed, and SCLC xenograft mice were treated with 90Y-anti-ROBO1 IgG. Tumor volume and body weight were periodically measured throughout the experiments. The tumors and organs of mice were then collected, and a pathological analysis was carried out.ResultsAs a result of the biodistribution study, we observed tumor uptake of 111In-anti-ROBO1 IgG. The liver, kidney, spleen, and lung showed comparably high accumulation of 111In-labeled anti-ROBO1. In the RIT study, 90Y-anti-ROBO1 IgG significantly reduced tumor volume compared with baseline. Pathological analyses of tumors revealed coagulation necrosis and fatal degeneration of tumor cells, significant reduction in the number of Ki-67-positive cells, and an increase in the number of apoptotic cells. A transient reduction of hematopoietic cells was observed in the spleen, sternum, and femur.ConclusionsThese results suggest that RIT with 90Y-anti-ROBO1 IgG is a promising treatment for ROBO1-positive SCLC. 相似文献
9.
《International journal of radiation applications and instrumentation. Part B, Nuclear medicine and biology》1988,15(6):717-720
Our laboratory investigated the use of a rapid miniaturized chromatography system, ITLC-SG with 0.9% NaCl, to assess the radiochemical purity of 111In labeled monoclonal antibodies (MoAbs). Radiochemical analysis was performed on numerous 111In labeled antibody preparations with labeling efficiencies ranging from 40 to greater than 95% and the results compared to those obtained with size exclusion high performance liquid chromatography (HPLC). The chromatographic procedure involved challenging radiolabeled antibodies with 0.05 M DTPA to chelate unbound and/or non-specific bound 111In, spotting on miniaturized instant thin layer-silica gel chromatography strips, developing in 0.9% NaCl, and counting appropriate segments for radioactivity. Results of the study demonstrated that the miniaturized chromatography procedure was rapid, taking less than 4 min to complete, and accurate in assessing the amount of unbound or non-specific bound 111In in 111In labeled monoclonal antibodies, when compared to size exclusion HPLC. 相似文献
10.
《International journal of radiation applications and instrumentation. Part B, Nuclear medicine and biology》1991,18(8):847-853
The in vivo localization of a monoclonal antibody A7 against a human colorectal cancer was studied in nude mice bearing human solid carcinomas, to evaluate potential applications of this antibody for radioimmunodetection of cancer. The tissue distribution of125I-labeled A7 MoAb at 3 days after i.v. injection into mice bearing five different kinds of human solid tumors revealed a high uptake ratio by colon cancer, mammary cancer, and glioblastoma. In contrast, the uptake ratio by murine colorectal cancer (Colon-38) was extremely low. In immunoscintigraphic studies, HCT-15, one of the human colon cancer, was clearly visualized with 111In-DTPA-A7 MoAb. Glioblastoma was also imaged with the same extent. These results suggest that A7 MoAb would be applicable to the in vivo radioimmunodetection of colon- and mammary-cancer, and of glioblastoma. 相似文献
11.
《International journal of radiation applications and instrumentation. Part B, Nuclear medicine and biology》1990,17(2):181-188
A scheme has been designed to synthesize a homologous series of new bifunctional chelating agents (BFCAs), which may increase the thermodynamic stability of metal chelates and conjugate at the specific sites on the monoclonal antibody molecule (MoAb) permitting us to analyze the structure-activity relationships of the series of compounds. Four such compounds have been prepared and chacterized by FT-i.r. and NMR spectroscopy. One of them has been used to label an antibody with 111In, the stability and distribution of which has been examined in tumor-bearing mice and compared to that of the 111In-MoAb prepared using cyclic anhydride of DTPA. Enhanced tumor/blood ratios (9 vs 6.5), tumour to muscle ratios (7 vs 3), and decreased liver uptake (4 vs 12%) have been obtained. 相似文献
12.
Diane E Milenic Karen J Wong Kwamena E Baidoo Tapan K Nayak Celeste AS Regino Kayhan Garmestani Martin W Brechbiel 《MABS-AUSTIN》2010,2(5):550-564
The potential of the HER2-targeting antibody trastuzumab as a radioimmunoconjugate useful for both imaging and therapy was investigated. Conjugation of trastuzumab with the acyclic bifunctional chelator CHX-A″-DTPA yielded a chelate:protein ratio of 3.4 ± 0.3; the immunoreactivity of the antibody unaffected. Radiolabeling was efficient, routinely yielding a product with high specific activity. Tumor targeting was evaluated in mice bearing subcutaneous (s.c.) xenografts of colorectal, pancreatic, ovarian and prostate carcinomas. High uptake of the radioimmunoconjugate, injected intravenously (i.v.), was observed in each of the models and the highest tumor %ID/g (51.18 ± 13.58) was obtained with the ovarian (SKOV-3) tumor xenograft. Specificity was demonstrated by the absence of uptake of 111In-trastuzumab by melanoma (A375) s.c. xenografts and 111In-HuIgG by s.c. LS-174T xenografts. Minimal uptake of i.v. injected 111In-trastuzumab in normal organs was confirmed in non-tumor-bearing mice. The in vivo behavior of 111In-trastuzumab in mice bearing intraperitoneal (i.p.) LS-174T tumors resulted in a tumor %ID/g of 130.85 ± 273.34 at 24 h. Visualization of tumor, s.c. and i.p. xenografts was achieved by γ-scintigraphy and PET imaging. Blood pool was evident as expected but cleared over time. The blood pharmacokinetics of i.v. and i.p. injected 111In-trastuzumab was determined in mice with and without tumors. The data from these in vitro and in vivo studies supported advancement of radiolabeled trastuzumab into two clinical studies, a Phase 0 imaging study in the Molecular Imaging Program of the National Cancer Institute and a Phase 1 radioimmunotherapy study at the University of Alabama.Key words: monoclonal antibody, HER2, trastuzumab, radioimmunodiagnosis, radioimmunotherapy 相似文献
13.
《International journal of radiation applications and instrumentation. Part B, Nuclear medicine and biology》1992,19(7):719-726
A monoclonal antibody, C-215, against colon cancer, was internally labelled with [75Se]methionine. The biodistribution was studied in tumour-bearing nude mice and compared with the biodistribution of [131I]C-215. The tissue uptake was divided into three parts: antibody bound to the antigen, antibody in the extracellular space and uptake of the released radionuclide. [75Se]C-215 showed a greater amount of antigen-bound antibody in the tumour, but also a greater unspecific uptake both in tumour and normal tissue. 相似文献
14.
Richard L. Wahl Barry S. Wilson Monica Liebert William H. Beierwaltes 《Cancer immunology, immunotherapy : CII》1987,24(3):221-224
Summary Nonspecific uptake of radiolabeled monoclonal antibodies in normal tissues is a significant problem for tumor imaging. A potential means of decreasing nonspecific antibody binding is to blockade nonspecific antibody binding sites by predosing with cold, nonspecific isotypematched antibody, before injecting specific antibody. Nontumor-specific murine monoclonal antibody LK2H10 (IgG1) or Ab-1 (IgG2a) was given i.v. at doses of 0 to 3.5 mg to nude mice with xenografts of human melanoma. These mice were then given i.v. 4 g of 131I anti-high molecular weight antigen of melanoma (HMWMAA) monoclonal antibody 763.24T (IgG1) or 225.28S (IgG2a), respectively. These mice were also given a tracer dose of 125I LK2H10 or Ab-1, respectively. Specific tumor uptake of anti-HMWMAA antibodies was see in all cases. No drop in tumor or nontumor uptake was demonstrated for either of the tumor-specific or nonspecific monoclonal antibodies due to nonspecific monoclonal antibody pretreatment. These data suggest that high doses of isotype-matched unlabeled nonspecific monoclonal antibody given before 131I tumor-specific monoclonal antibody, will not enhance tumor imaging.
Present address: Hybritech, San Diego, CA, USA 相似文献
15.
Suzanne A. Eccles Helen P. Purvies Jennifer M. Styles Stephen M. Hobbs Christopher J. Dean 《Cancer immunology, immunotherapy : CII》1989,30(1):5-12
Summary The object of our current investigations is to explore the potential of antibodies for localisation and treatment of disseminated disease, using as a model rat monoclonal antibodies (mAbs) raised against syngeneic tumourspecific antigens. As part of this study, antibodies of differing isotypes with specificity for either HSN or MC24 sarcoma were labelled with125iodine and injected intravenously into normal rats or those bearing paired tumours in contralateral flanks. The blood clearance rates of the radiolabelled antibodies were found to be influenced by immunoglobulin subclass (IgG2b > IgG2a > IgG1) and to be increased non-specifically by the presence of growing tumours. The tumour and normal tissue distributions of the antibodies tested were also found to vary according to their apparent degree of interaction with host Fc-receptor-bearing cells, to the extent that tumour specificity in vitro was not necessarily reflected in selectivity of localisation in vivo. Three IgG2b monoclonal antibodies showed preferential uptake in the spleens of syngeneic rats and non-specific accumulation in tumours. This effect was not observed with antibodies of IgG2a or IgG1 subclass, and was abolished by the use of IgG2b F(ab)2 preparations. In spite of the use of immunoglobulin fragments, varying the assay time and testing tumours of different sizes, specific tumour localisation was low with all seven monoclonal antibodies tested. The maximum uptake achieved was less than 1% of the injected dose of antibody per gram of tumour. Much higher levels of antibody localisation have been reported for human tumour xenografts growing in nude mice, but these are rarely achieved in other systems. We propose that the use of autologous monoclonal antibodies recognising tumour-associated antigens of relatively low epitope density in syngeneic hosts provides a valid alternative model in which to investigate the factors limiting more effective, specific immunolocalisation of malignant disease. 相似文献
16.
《International journal of radiation applications and instrumentation. Part B, Nuclear medicine and biology》1991,18(5):519-526
Monoclonal antibody (mAb) 10B, directed against the human ovarian adenocarcinoma cell line, HEY, was conjugated with cyclic DTPA anhydride and labelled with 111In. The biodistribution of 111In-DTPA-10B was determined in non-tumour bearing mice and mice bearing subcutaneous (s.c.) and intraperitoneal (i.p.) HEY tumours. The radiolabel was preferentially targeted to s.c. and i.p. tumours in comparison with a control mAb, 111In-DTPA-2G3, which does not bind to HEY cells. Among normal organs, the predominant uptake of radiolabel was into liver and kidney. Subcutaneous tumours were successfully imaged using external gamma scintigraphy following i.v. injection of 111In-DTPA-10B. The results suggest that 111In-DTPA-10B may be a useful agent for the diagnostic imaging of tumour masses in patients with ovarian cancer. 相似文献
17.
Derk Berends Joseph L. M. van Gaalen Els H. Rhijnsburger Nico J. de Both Wouter Breeman Willem H. Bakker Peter Kooy 《Cancer immunology, immunotherapy : CII》1988,26(3):243-249
Summary The binding of the syngeneic monoclonal antibodies IC5F5 and 4D2B4 to Rauscher virus-induced myeloid leukemic (RMB-1) cells was analyzed in vivo in tumor-bearing BALB/c mice. To verify it these antibodies bind specifically to RMB-1 cells, purified antibodies were iodinated with the isotopes 125I and 131I. Mice previously inoculated with tumor cells were injected with these labeled monoclonal antibodies and the plasma clearance and the tissue distribution were determined. The clearance in tumor-bearing animals was faster than in control mice. The tissue distribution was corrected for nonspecific accumulation by scoring for an unrelated antibody. Calculation of a localization index showed that IC5F5 binds at least 4.5 times more specifically to tumor cells than to other tissues. A preferential localization of radioactivity in s.c. tumor tissue was seen in the scanning of animals injected with 131I-labeled antibodies. The most direct proof of specific binding was observed in autoradiograms of animals treated with 125I-labeled antibodies. Small islands of tumor cells in the livers of mice inoculated i.v. had a high density of grains compared to other tissues and also compared to tumor cells in mice treated with unrelated monoclonal antibodies. These results show efficient targeting of these monoclonal antibodies and make immunotherapy of these myeloid leukemic cells possible. 相似文献
18.
Otto C. Boerman Robert M. Sharkey George Y. Wong Rosalyn D. Blumenthal Rosarito L. Aninipot David M. Goldenberg 《Cancer immunology, immunotherapy : CII》1992,35(2):127-134
Summary The biodistributions of three131I-labeled murine monoclonal antibodies, NP-4 and Immu-14 anti-(carcinoembryonic antigen), and Mu-9 anti-(colon-specific antigen p), were determined at antibody protein doses varying from 1 µg to 1000 µg in nude mice with small (0.1–0.4 g) GW-39 human colonic cancer xenografts. For each antibody, the percentage of the injected dose per gram of tumor and tumor/nontumor ratios were constant over a wide protein dose range. However, at high protein doses (above 100 µg for NP-4 and Immu-14) the percentage of the injected dose per gram of tumor and tumor/nontumor ratios decreased. Assuming that the uptake of a control anti-(-fetoprotein) antibody represents the amount of antibody that accumulates in the tumor nonspecifically (i.e., antigen-independently), it could be shown that for each antibody the amount of antibody protein that accumulates in the tumor specifically, increases linearly with the protein dose, reaching a plateau level at the highest doses tested. The growth inhibition of GW-39 tumor transplants in nude mice treated with131I-labeled antibody at either low or high antibody protein dose was compared. These experiments indicated that, in this experimental model, enhanced antibody protein dose may decrease the therapeutic efficacy of radioiodinated antibodies. It is suggested that heterogeneous distribution at low protein dose, with intense localization around the blood vessels, may enhance the tumoricidal effect of radioantibodies.Supported in part by USPHS grants CA 39 841 and CA 37 895, National Institutes of Health and Human ServicesResearch fellow of the Dutch Cancer Society 相似文献
19.
P C Srivastava D J Buchsbaum J F Allred P G Brubaker D E Hanna J K Spicker 《BioTechniques》1990,8(5):536-545
A new radioiodinating agent, N-(p-[125I]iodophenyl)maleimide, has been synthesized for its potential utility in the radioiodination of monoclonal antibodies and other proteins. The efficiency of incorporation of 125I in the B72.3 antibody by iodine monochloride iodination or by maleimide conjugation was 19% and 43%, respectively. The thyroid uptake following intraperitoneal administration of the two 125I-labeled antibody preparations was evaluated in nude mice implanted with LS174T colon carcinoma xenografts. The iodine monochloride preparation showed substantially greater uptake in the thyroid with values of 2.1% ID at 6 h after injection and reaching a maximum of 4.3% ID after 6 days. In contrast, the maleimide preparation showed a uniformly low uptake in thyroid of 0.1%-0.2% ID. The results of these preliminary studies demonstrate that the N-(p-[125I]iodophenyl)maleimide-labeled monoclonal antibodies showed markedly less (less than 10-fold) uptake of radioiodine in the thyroid, indicating significantly less in vivo deiodination than iodine monochloride-labeled monoclonal antibodies, while retaining some tumor localization in vivo. Studies are in progress to optimize N-(p-[125I]iodophenyl)maleimide radioiodination conditions and to improve the tumor localization. 相似文献
20.
Subbiah K Rayala SK Ananthanarayanan M Thangarajan R 《Indian journal of experimental biology》2001,39(10):993-997
In vivo tumor targetting with radiolabelled monoclonal antibodies is a promising approach for the diagnosis and therapy of tumors. A specific monoclonal antibody (mAb), DLAB was generated to the Dalton's lymphoma associated antigen (DLAA) from Haemophilus paragallinarum-induced spontaneous fusion. In order to study the tumor localisation and biodistribution properties of the monoclonal antibody, scintigraphic studies were performed using the radiolabelled DLAB. 131-labelled DLAB was administered intravenously into Swiss mice bearing Dalton's lymphoma and external scintiscanning was performed at different time intervals. Clear tumor images were obtained which revealed selective and specific uptake of radiolabel and the results were compared with biodistribution data. The radioiodinated monoclonal antibody showed fast tumor uptake which increased significantly to 14.6% injected dose (ID)/g at 12 hr post-injection. Enhanced blood clearance of radioactivity resulted in higher tumor/blood ratio of 5.96 at 48 hr. 131I-labelled DLAB resulted in selective and enhanced uptake of the radioactivity by the tumor compared to the non-specific antibody and the results suggest the potential use of spontaneous fusion for producing specific monoclonal antibodies for tumor detection and therapy. 相似文献