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Sample records for indium-111 antimyosin monoclonal

  1. Pharmacokinetics of indium-111-labeled antimyosin monoclonal antibody in murine experimental viral myocarditis

    International Nuclear Information System (INIS)

    Yamada, T.; Matsumori, A.; Watanabe, Y.; Tamaki, N.; Yonekura, Y.; Endo, K.; Konishi, J.; Kawai, C.

    1990-01-01

    The pharmacokinetics of indium-111-labeled antimyosin monoclonal antibody Fab were investigated with use of murine experimental viral myocarditis as a model. The biodistribution of indium-111-labeled antimyosin antibody Fab on days 3, 5, 7, 14, 21 and 28 after encephalomyocarditis virus inoculation demonstrated that myocardial uptake increased significantly on days 5, 7 and 14 (maximum on day 7) in infected versus uninfected mice (p less than 0.001). In vivo kinetics in infected mice on day 7 demonstrated that the heart to blood ratio reached a maximum 48 h after the intravenous administration of indium-111-labeled antimyosin Fab, which was considered to be the optimal time for scintigraphy. The scintigraphic images obtained with indium-111-labeled antimyosin Fab demonstrated positive uptake in the cardiac lesion in infected mice. The pathologic study demonstrated that myocardial uptake correlated well with pathologic grades of myocardial necrosis. High performance liquid chromatography revealed the presence of an antigen-antibody complex in the circulation of infected mice after the injection of indium-111-labeled antimyosin Fab. This antigen bound to indium-111-labeled antimyosin Fab in the circulation might be whole myosin and this complex may decrease myocardial uptake and increase liver uptake. It is concluded that indium-111-labeled antimyosin monoclonal antibody Fab accumulates selectively in damaged heart tissue in mice with acute myocarditis and that indium-111-labeled antimyosin Fab scintigraphy may be a useful method for the visualization of acute myocarditis

  2. Acute myocardial infarct imaging with indium-111-labeled monoclonal antimyosin Fab

    International Nuclear Information System (INIS)

    Khaw, B.A.; Yasuda, T.; Gold, H.K.; Leinbach, R.C.; Johns, J.A.; Kanke, M.; Barlai-Kovach, M.; Strauss, H.W.; Haber, E.

    1987-01-01

    Indium-111 monoclonal antimyosin Fab scintigraphy was used to detect myocardial necrosis in 52 of 54 patients (96.3%) with acute myocardial infarction. Infarcts were visualized when coronary arteries were persistently occluded (n = 10), became patent after thrombolysis (n = 33), or became patent after spontaneous reperfusion (n = 7). Posteroinferolateral visualizations were obtained in two patients with clinical and enzymatic evidence of infarction but normal electrocardiograms. Of the two patients in whom no infarcts were visualized, one had an anterior myocardial infarct. This patient underwent successful thrombolytic therapy, with attendant minimization of creatine kinase release. The other patient had a small, nonreperfused inferior myocardial infarct. Five patients with a history of remote infarction and acute necrosis showed antimyosin uptake only in regions concordant with the acute episodes of infarction, and radiolabeled antimyosin Fab localized in neither old infarcts nor normal, noninfarcted myocardium. Antimyosin Fab scintigraphy, thus, appears to be a highly specific means of delineating necrotic myocardium, at least in this limited and selected group of patients

  3. Imaging of acute myocardial infarction in pigs with Indium-111 monoclonal antimyosin scintigraphy and MRI

    International Nuclear Information System (INIS)

    Kate, C.I.; Kroonenburgh, M.J. van; Schipperheyn, J.J.; Doornbos, J.; Hoedemaeker, P.J.; Maes, A.; Nat, K.H. van der; Camps, J.A.; Huysmans, H.A.; Pauwels, E.K.

    1990-01-01

    Indium-111 antimyosin F(ab')2 was used in a series of scintigraphic studies on experimentally induced myocardial infarctions in pigs. Antimyosin distribution recorded by planar images of in vivo pigs and by single photon emission computed tomography (SPECT) of excised hearts delineated areas of myocardial necrosis if infarct volume exceeded 3.3 cm3. Scintigraphic images were compared with magnetic resonance images (MRI) obtained from excised hearts and with photographs of slices of the hearts. Infarct size and localization determined with antimyosin were compared. The MR images, with or without gadolinium-DTPA (Gd-DTPA), of the in vivo pigs were all false-negative; some myocardial wall thinning and high bloodpool signals were visible. Results show that both the antimyosin and the MR technique are specific methods for the visualization of induced myocardial necrosis in this animal model. However, the use of antimyosin is limited to a period ranging from 24 to 72 hours after infarction

  4. Measurement of infarct size and percentage myocardium infarcted in a dog preparation with single photon-emission computed tomography, thallium-201, and indium 111-monoclonal antimyosin Fab

    International Nuclear Information System (INIS)

    Johnson, L.L.; Lerrick, K.S.; Coromilas, J.

    1987-01-01

    Single photon-emission tomography (SPECT) and indium 111-labeled monoclonal antimyosin Fab fragments were used to measure myocardial infarct size in 12 dogs, six subjected to balloon catheter-induced coronary artery occlusion for 6 hr (late reperfusion) and six subjected to occlusion with reperfusion at 2 hr (early reperfusion). Tomographic imaging was performed 24 hr after the intravenous injection of labeled Fab fragments with the use of a dual-head SPECT camera with medium-energy collimators. Immediately after the first tomographic scan, thallium-201 was injected into nine of 12 dogs and imaging was repeated. Estimated infarct size in grams was calculated from transaxially reconstructed, normalized, and background-corrected indium SPECT images with the use of a threshold technique for edge detection. Estimated noninfarcted myocardium in grams was calculated from obliquely reconstructed thallium SPECT images by a similar method. The animals were killed and infarct size in grams and true infarct size as a percentage of total left ventricular myocardial volume were measured by triphenyl tetrazolium chloride staining. Estimated infarct size from indium SPECT images showed an excellent correlation with true infarct size (r = .95, SEE = 4.1 g). Estimated percentage myocardium infarcted was calculated by dividing estimated infarct size from indium images by the sum of estimated infarct size plus estimated noninfarcted myocardium obtained from thallium images. Correlation between the estimated percentage of myocardium infarcted and true percentage of myocardium infarcted was excellent

  5. Indium111 antimyosin for the detection of leiomyosarcoma and rhabdomyosarcoma

    International Nuclear Information System (INIS)

    Cox, P.H.; Pillay, M.; Schonfeld, D.; Verweij, J.; Stoter, G.

    1988-01-01

    111 In-antimyosin monoclonal antibody complex passes through damaged myocardial cell membranes and binds to the intracellular myosin. Normal myocardial and other muscle cells show no uptake. Rhabdomyosarcoma and Leiomyosarcoma cells also contain intracellular myosin and the cell membrane permeability is greater than normal. Significant uptake of 111 In-antimyosin was observed in patients with Leiomyosarcoma and Rhabdomyosarcoma suggesting that the reagent has a potential for the in vivo detection of these tumour types. Tumour to background ratios of 10:1 were measured in one case and in view of the fact that the site of accumulation is intracellular, antimyosin may have a potential as a carrier for therapeutic agents. (orig.)

  6. The role of indium-111 antimyosin (Fab) imaging as a noninvasive surveillance method of human heart transplant rejection

    International Nuclear Information System (INIS)

    De Nardo, D.; Scibilia, G.; Macchiarelli, A.G.

    1989-01-01

    The identification of rejection after heart transplantation in patients receiving cyclosporine immunosuppressive therapy requires the endomyocardial biopsy, an invasive method associated with a finite morbidity. To evaluate the role of indium-111 antimyosin (Fab) scintigraphy as a noninvasive surveillance method of heart transplant rejection, the Fab fragment of murine monoclonal antimyosin antibodies labeled with indium-111 was administered intravenously in 30 scintigraphic studies to 10 consecutive heart transplant recipients. Endomyocardial biopsy specimens were obtained 72 hours after each scintigraphic study. Nineteen scintigraphic studies had negative findings; no false negative finding was obtained. Eleven antimyosin scintigraphic studies had positive findings, and in these studies endomyocardial biopsy revealed mild rejection in two cases, moderate acute rejection with myocyte necrosis in two cases, myocyte necrosis as a consequence of ischemic injury in six cases, and possibly cytotoxic damage in one case. Antimyosin scintigraphy may represent a reliable screening method for the surveillance of heart transplant patients. In the presence of a negative finding from antimyosin scintigraphy, it may be possible to avoid endomyocardial biopsy. Conversely, in patients who have a positive finding from antimyosin scintigraphy, the endomyocardial biopsy is mandatory to establish the definitive diagnosis by histologic examination of the myocardium

  7. Lyme myocarditis diagnosed by indium-111-antimyosin antibody scintigraphy

    Energy Technology Data Exchange (ETDEWEB)

    Casans, I.; Villar, A.; Almenar, V.; Blanes, A.

    1989-06-01

    We report a new case of Lyme disease with cardiac manifestations, which has been possible to follow during the long period of 12 years. We have detected the usual ECG abnormalities, and concentric hypertrophic myocardiopathy, by echocardiography. The acute myocarditis was demonstrated by /sup 111/In-antimyosin scintigraphy, which showed global myocardial uptake of the tracer, constituting the first report, to our knowledge, of Lyme myocarditis diagnosed by this method.

  8. Lyme myocarditis diagnosed by indium-111-antimyosin antibody scintigraphy

    International Nuclear Information System (INIS)

    Casans, I.; Villar, A.; Almenar, V.; Blanes, A.

    1989-01-01

    We report a new case of Lyme disease with cardiac manifestations, which has been possible to follow during the long period of 12 years. We have detected the usual ECG abnormalities, and concentric hypertrophic myocardiopathy, by echocardiography. The acute myocarditis was demonstrated by 111 In-antimyosin scintigraphy, which showed global myocardial uptake of the tracer, constituting the first report, to our knowledge, of Lyme myocarditis diagnosed by this method. (orig.)

  9. Indium-111-monoclonal antimyosin antibody studies after the first year of heart transplantation. Identification of risk groups for developing rejection during long-term follow-up and clinical implications

    International Nuclear Information System (INIS)

    Ballester, M.; Obrador, D.; Carrio, I.; Auge, J.M.; Moya, C.; Pons-Llado, G.; Caralps-Riera, J.M.

    1990-01-01

    The long-term clinical course and results of biopsies in 21 patients studied with monoclonal antimyosin antibodies more than 12 months after heart transplantation according to the presence and degree of antimyosin-antibody uptake is described. Eighteen men and three women aged 20-52 years (39 +/- 9 years) were studied with antimyosin antibodies 12-40 months (mean, 22 +/- 9 months) after heart transplantation, and followed for a mean of 18 months (10-28 months). The number of biopsies performed during follow-up was 102. Results showed normal antimyosin-antibody studies in nine patients and abnormal studies in 12 patients. Myocyte damage was identified in 18 of the 102 biopsies (17.6%), one in the normal antimyosin-antibody group of patients and 17 in those patients with myocardial antimyosin-antibody uptake. Patients who developed rejection comprised 11% and 67% of each respective group; the mean number of rejection episodes per patient was 0.11 +/- 0.33 and 1.41 +/- 1.41, respectively (p less than 0.01). A trend was noted by which higher heart-to-lung ratios were associated with greater probability of rejection. Conclusively, (1) antimyosin-antibody studies performed after more than 1 year after heart transplantation indicate the presence and level of rejection activity, (2) groups of patients at risk for developing rejection at biopsy during long-term follow-up may be detected by antimyosin-antibody study, and (3) surveillance for rejection and the degree of immunosuppression should be tailored to meet individual patient needs

  10. Indium-111-labelled antimyosin antibody imaging in a patient with cardiac sarcoidosis

    International Nuclear Information System (INIS)

    Knapp, W.H.; Bentrup, A.; Ohlmeier, H.

    1993-01-01

    The aetiology of cardiac dysfunction caused by sarcoid granulomatous inflammation may be difficult to clarify, and the potential of imaging methods is limited. We report on a patient who present with acute biventricular decompensation. Pulmonary sarcoidosis was confirmed after hospitalization. Four weeks after the initiation of corticosteroid treatment, scintigraphy with indium-111-labelled antimyosin antibody Fab fragments (AMAB) revealed distinct activity accumulation in major parts of the left ventricular wall (heart-lung ratio: 1.6) 72 h following injection. There may by a role for AMAB scintigraphy in the early detection of cardiac sacroidosis. (orig.)

  11. Measurement of acute Q-wave myocardial infarct size with single photon emission computed tomography imaging of indium-111 antimyosin.

    Science.gov (United States)

    Antunes, M L; Seldin, D W; Wall, R M; Johnson, L L

    1989-04-01

    Myocardial infarct size was measured by single photon emission computed tomography (SPECT) following injection of indium-111 antimyosin in 27 patients (18 male and 9 female; mean age 57.4 +/- 10.5 years, range 37 to 75) who had acute transmural myocardial infarction (MI). These 27 patients represent 27 of 35 (77%) consecutive patients with acute Q-wave infarctions who were injected with indium-111 antimyosin. In the remaining 8 patients either tracer uptake was too faint or the scans were technically inadequate to permit infarct sizing from SPECT reconstructions. In the 27 patients studied, infarct location by electrocardiogram was anterior in 15 and inferoposterior in 12. Nine patients had a history of prior infarction. Each patient received 2 mCi of indium-111 antimyosin followed by SPECT imaging 48 hours later. Infarct mass was determined from coronal slices using a threshold value obtained from a human torso/cardiac phantom. Infarct size ranged from 11 to 87 g mean 48.5 +/- 24). Anterior infarcts were significantly (p less than 0.01) larger (60 +/- 20 g) than inferoposterior infarcts (34 +/- 21 g). For patients without prior MI, there were significant inverse correlations between infarct size and ejection fraction (r = 0.71, p less than 0.01) and wall motion score (r = 0.58, p less than 0.01) obtained from predischarge gated blood pool scans. Peak creatine kinase-MB correlated significantly with infarct size for patients without either reperfusion or right ventricular infarction (r = 0.66). Seven patients without prior infarcts had additional simultaneous indium-111/thallium-201 SPECT studies using dual energy windows.(ABSTRACT TRUNCATED AT 250 WORDS)

  12. Determination of infarct size of acute myocardial infarction in dogs by magnetic resonance imaging and gadolinium-DTPA: Comparison with indium-111 antimyosin imaging

    International Nuclear Information System (INIS)

    Nishimura, T.; Yamada, Y.; Hayashi, M.; Kozuka, T.; Nakatani, T.; Noda, H.; Takano, H.

    1989-01-01

    Acute myocardial infarctions were produced in nine dogs by ligation of the left anterior descending coronary artery. Twenty-four hours after ligation, 0.5 mM/kg of gadolinium (Gd)-DTPA was injected intravenously, followed by cardiectomy 30 min later. Indium-111 antimyosin was administered intravenously 6 hr before cardiectomy to compare the infarct size with Gd-DTPA contrast enhancement. Areas of Gd-DTPA contrast enhancement were closely correlated with those of indium-111 antimyosin uptake (r = .86), although the former showed slightly greater than the latter. Partial and complete enhancements were observed in three and six dogs, respectively. In the T1 and T2 maps, T1 relaxation times of the infarcted area showed greater T1 shortening compared with normal myocardium, whereas T2 relaxation times were not different between infarcted and normal myocardium. Thus, Gd-DTPA showed significant contrast enhancement of the infarcted area because of greater T1 shortening and the extent of Gd-DTPA contrast enhancement expressed the infarct size precisely

  13. Evaluation of indium-111-labeled antifibrin monoclonal antibody for the diagnosis of venous thrombotic disease

    International Nuclear Information System (INIS)

    De Faucal, P.; Peltier, P.; Planchon, B.; Dupas, B.; Touze, M.D.; Baron, D.; Scaible, T.; Berger, H.J.; Chatal, J.F.

    1991-01-01

    The potential advantage of using 111 In-antifibrin ( 111 In-AF) monoclonal antibody for the diagnosis of deep venous thrombosis (DVT) was studied in 44 patients with suspected DVT (27 underwent heparin therapy before 111 In-AF injection). All patients had contrast venography (considered as the gold standard) and 111 In-AF scintigraphy within 24 hr. Two to 3 mCi of 111 In-AF were injected intravenously, and planar scintigraphy of the limbs was recorded within 10 min (17 times), 3 hr (44 times), and 18 hr (39 times). Indium-111-AF images were then interpreted without knowledge of the results of the other examinations. The DVT diagnostic accuracy of 111 In-AF was greater when interpretation was based on images recorded at different time periods after injection. Indium-111-AF sensitivity for diagnosis of DVT was 85% (29/34) and was not apparently decreased by heparin therapy. None of the 10 patients with negative contrast venography had a positive 111 In-AF scan. The results demonstrate the importance of recording serial images and the excellent accuracy of 111 In-AF for diagnosing DVT

  14. Antimyosin monoclonal antibodies for early detection of cardiac allograft rejection

    International Nuclear Information System (INIS)

    Schuetz, A.; Fritsch, S.; Kemkes, B.M.; Kugler, C.; Angermann, C.; Spes, C.; Anthuber, M.; Weiler, A.; Wenke, K.; Gokel, J.M.

    1990-01-01

    Sixty-eight indium 111-labeled antimyosin Fab-DTPA imaging studies (0.5 mg intravenously with a radioactivity of 65 to 75 MBq) were executed on 37 of 116 patients undergoing heart transplantation to assess diagnostic accuracy and clinical utility. As controls, 21 patients with cardiomyopathy (n = 8), unstable angina (n = 9), and myocardial infarction (n = 4) were selected. After 48 hours, single photon emission computed tomographic images were evaluated visually, and heart/lung ratios were measured, using the region of interest technique. They were compared with echocardiographic and endomyocardial biopsy results. In 40 studies a heart/lung ratio less than or equal to 1.6 corresponded to a negative biopsy result in 98% (40/41). Echocardiography enabled correct identification of 95% of the patients with normal biopsy findings. In 91% (22/24) a positive biopsy finding correlated with a heart/lung ratio greater than 1.6 including 20 mild rejections, but in only 64%, with an increase in wall thickness and/or decrease of fractional diameter shortening seen on echocardiogram. In addition, the various stages of rejection episodes determined the amount of the heart-lung ratio. There was a significant relationship between the histologic findings and the antimyosin uptake. In 13 patients a second investigation was performed after rejection therapy. All patients had a negative biopsy result, and the heart/lung ratio decreased to normal ranges (less than or equal to 1.6). Five antimyosin antibody studies were excluded, as in these cases, negative uptake results were found during rejection therapy with high-dose steroids. The overall sensitivity was calculated at 93% and the specificity at 98%

  15. Detection of experimental myocarditis by monoclonal antimyosin antibody, Fab fragment

    Energy Technology Data Exchange (ETDEWEB)

    Rezkalla, S.; Kloner, R.A.; Khaw, B.A.; Haber, E.; Fallon, J.T.; Smith, F.E.; Khatib, R.

    1989-02-01

    The purpose of this study was to determine whether monoclonal antimyosin Fab (antigen binding fragment) was capable of labeling hearts with experimental coxsackievirus myocarditis, and to determine whether Fab could be used for detecting myocardial damage in either early or chronic phases of the disease. Sixty-five, 3-week-old cesarean-derived 1 (CD 1) mice were divided into two groups: group I (noninfected animals) and group II (infected with coxsackievirus B3). Mice from each group were killed on days 7, 17, 30, or 90 of infection. Forty-eight hours before killing, mice were injected with monoclonal I-125 antimyosin, Fab (25 microCi/injection) and radioactivity was counted in the heart. Selected heart sections were also examined by autoradiography. Heart radioactivity, count/m/mg (m +/- SEM) on days 7, 17, 30, and 90 of infection was 10.8 +/- 1.7, 21.3 +/- 1.1, 11.2 +/- 3.4, and 12.4 +/- 1.5 for group I, versus 36.7 +/- 8.0 (p less than 0.01), 50.0 +/- 4.5 (p less than 0.001), 33.4 +/- 16.1 (p = NS), and 40.6 +/- 8.5 (p less than 0.01) for group II, respectively. Autoradiography revealed focal uptake within areas of necrotic myocardium. We conclude that I125 Fab may be useful in detecting myocardial damage in the experimental model of murine myocarditis up to day 90 of infection.

  16. Detection of experimental myocarditis by monoclonal antimyosin antibody, Fab fragment

    International Nuclear Information System (INIS)

    Rezkalla, S.; Kloner, R.A.; Khaw, B.A.; Haber, E.; Fallon, J.T.; Smith, F.E.; Khatib, R.

    1989-01-01

    The purpose of this study was to determine whether monoclonal antimyosin Fab (antigen binding fragment) was capable of labeling hearts with experimental coxsackievirus myocarditis, and to determine whether Fab could be used for detecting myocardial damage in either early or chronic phases of the disease. Sixty-five, 3-week-old cesarean-derived 1 (CD 1) mice were divided into two groups: group I (noninfected animals) and group II (infected with coxsackievirus B3). Mice from each group were killed on days 7, 17, 30, or 90 of infection. Forty-eight hours before killing, mice were injected with monoclonal I-125 antimyosin, Fab (25 microCi/injection) and radioactivity was counted in the heart. Selected heart sections were also examined by autoradiography. Heart radioactivity, count/m/mg (m +/- SEM) on days 7, 17, 30, and 90 of infection was 10.8 +/- 1.7, 21.3 +/- 1.1, 11.2 +/- 3.4, and 12.4 +/- 1.5 for group I, versus 36.7 +/- 8.0 (p less than 0.01), 50.0 +/- 4.5 (p less than 0.001), 33.4 +/- 16.1 (p = NS), and 40.6 +/- 8.5 (p less than 0.01) for group II, respectively. Autoradiography revealed focal uptake within areas of necrotic myocardium. We conclude that I125 Fab may be useful in detecting myocardial damage in the experimental model of murine myocarditis up to day 90 of infection

  17. Detection of deep venous thrombosis with indium 111-labelled monoclonal antibody against tissue plasminogen activator

    Energy Technology Data Exchange (ETDEWEB)

    Tromholt, N.; Hesse, B. (Hilleroed County Hospital (Denmark). Dept. of Clinical Physiology); Folkenborg, O. (Isotope-Pharmcy, Broenshoej (Denmark)); Selmer, J. (Novo Industri A/S, Bagsvaerd (Denmark)); Nielsen, N.T. (Hilleroed County Hospital (Denmark). Dept. of Radiology)

    1991-05-01

    The administration of a radiolabelled monoclonal antibody against tissue plasminogen activator allows detection of areas with increased fibrinolytic activity, i.e. those with an active thrombotic lesion. Eight patients with phlebographically verified deep venous thrombosis were examined. At the time of immunoscintigraphy study they were examined receiving anticoagulant therapy. Some 75-85 MBq {sup 111}In-labelled antibody were injected, and scintigrams were obtained after 30 min and after 24 h. The precise site of the thrombus could not be visualized after 30 min due to high background activity, whereas after 24 h it was detectable in all patients. The thrombus/background ratios achieved are twice as high as those observed in a human antifibrin antibody study. These preliminary data suggest a high sensitivity of our PA-specific antibody for the detection of active deep venous thrombosis in man, and our antibody seems to offer theoretical advantages over both platelet and fibrin-specific antibodies. (orig.).

  18. Detection of deep venous thrombosis with indium 111-labelled monoclonal antibody against tissue plasminogen activator

    International Nuclear Information System (INIS)

    Tromholt, N.; Hesse, B.; Selmer, J.; Nielsen, N.T.

    1991-01-01

    The administration of a radiolabelled monoclonal antibody against tissue plasminogen activator allows detection of areas with increased fibrinolytic activity, i.e. those with an active thrombotic lesion. Eight patients with phlebographically verified deep venous thrombosis were examined. At the time of immunoscintigraphy study they were examined receiving anticoagulant therapy. Some 75-85 MBq 111 In-labelled antibody were injected, and scintigrams were obtained after 30 min and after 24 h. The precise site of the thrombus could not be visualized after 30 min due to high background activity, whereas after 24 h it was detectable in all patients. The thrombus/background ratios achieved are twice as high as those observed in a human antifibrin antibody study. These preliminary data suggest a high sensitivity of our PA-specific antibody for the detection of active deep venous thrombosis in man, and our antibody seems to offer theoretical advantages over both platelet and fibrin-specific antibodies. (orig.)

  19. Thrombus imaging with indium-111 and iodine-131-labeled fibrin-specific monoclonal antibody and its F(ab')2 and Fab fragments

    International Nuclear Information System (INIS)

    Rosebrough, S.F.; Grossman, Z.D.; McAfee, J.G.

    1988-01-01

    We have previously reported successful imaging of fresh (2-4 hr old) and aged (1-5 days old) canine thrombi with 131 I-labeled intact monoclonal antibody (MAb) specific for fibrin. We now report thrombus imaging with 131 I-labeled F(ab')2 and Fab and 111 In-labeled intact MAb, F(ab')2, and Fab. Indium-111-labeled F(ab')2 proved to be the best imaging agent due to less nonspecific binding in the liver than whole IgG. Image quality was improved by the higher administered dose permissible with 111 In and its better physical characteristics for imaging, compared to 131 I. Immunofluorescence of fresh human histologic sections showed intact MAb and F(ab')2 binding to thrombi, pulmonary emboli, and atherosclerotic plaques, strengthening the feasibility of clinical thrombus imaging

  20. In vivo imaging and quantitation of renal transplant rejection using indium-111 labelled anti-lymphocyte and anti-MHC class I and II monoclonal antibodies in a rat model

    International Nuclear Information System (INIS)

    Loutfi, I.; Batchelor, J.R.; Lavender, J.P.

    1992-01-01

    It has been described in this report, non-invasive and specific method for imaging and assessment of acute kidney transplant rejection in rat model. This model can serve as a basis for application in man using a cocktail of monoclonal antibodies with different specificities starting with monoclonal antibodies labelled with indium-111 which have been used in this technique. 3 refs., 1 tab., 2 figs

  1. Sequential use of indium-111 labeled monoclonal antibodies 96.5 and ZME-018 does not increase detection sensitivity for metastatic melanoma

    International Nuclear Information System (INIS)

    Frontiera, M.; Murray, J.L.; Lamki, L.

    1989-01-01

    Two indium-111 labeled anti-melanoma murine monoclonal antibodies (MAb), 96.5 and ZME-018, each recognizing separate antigens on melanoma cells, were administered intravenously to 17 patients with melanoma in a sequential fashion to determine whether: (1) additional tumor sites could be imaged with the combination compared to a single Mab; (2) the first MAb influenced the biodistribution and tumor localization of the second; and (3) significantly toxicity occurred with the combination. Patients were randomized to receive either 96.5, followed by ZME-018, ZME-018 followed by 96.5, or each MAb followed by itself (controls). Infusions of the second MAb occurred 10 days after the first infusion. Gamma camera images were obtained 72 hours after each antibody infusion. There were 139 known metastatic sites of which 72 lesions were localized by either MAb for an overall sensitivity of 52%. The detection rate was higher when lesions only greater than 1.5 cm were considered. Imaging results were independent of MAb administration sequence. When ZME-018 was given as the first infusion, when ZME-018 was given as a second infusion (p = NS). However, mean sensitivities using 96.5 as the first or second infusion were 48% and 66% respectively (p = NS). There was not a significant number of sites detected by MAb 2 that were missed by MAb 1. Human anti-murine antibody (HAMA) response occurred in seven of eight patients studied; two patients who experienced toxicity had levels of HAMA greater than 2000 ng/ml. We conclude that the use of these two murine anti-melanoma monoclonal antibodies given in sequential fashion did not significantly change the imaging sensitivity from that seen with each individual antibody

  2. In vitro stability of EDTA and DTPA immunoconjugates of monoclonal antibody 2G3 labeled with indium-111

    Energy Technology Data Exchange (ETDEWEB)

    Reilly, R.; Lee, N.; Houle, S. (The Toronto Hospital (Canada)); Law, J.; Marks, A. (Toronto Univ., ON (Canada))

    1992-08-01

    Monoclonal antibody 2G3 directed against a high molecular weight glycoprotein on breast and ovarian cancer cells was conjugated with bicyclic DTPA (or EDTA) anhydride or benzyl isothiocyanate DTPA (benzyl DTPA) and labeled with {sup 111}In. DTPA anhydride was more reactive with the antibody than benzyl DTPA, and kinetics of labeling with {sup 111}In were more rapid for DTPA substituted 2G3 than for benzyl DTPA substituted 2G3. On the other hand, {sup 111}In-2G3 conjugates prepared using DTPA anhydride were subject to more extensive dimerization and higher losses in immunoreactivity than those prepared using benzyl DTPA. On the basis of measurement of transchelation to transferrin, the stability of {sup 111}In-2G3 prepared using DTPA anhydride or benzyl DTPA did not differ during incubation in human plasma for 6 days at 37{sup o}C. These results suggest that an important advantage of benzyl DTPA over DTPA anhydride for preparing {sup 111}In-labeled antibodies is the prevention of intermolecular (and intramolecular) crosslinking during conjugation which ultimately leads to alterations in conformation and losses in immunoreactivity of the radioimmunoconjugate. (author).

  3. Indium-111-labeled B72. 3 monoclonal antibody in the detection and staging of breast cancer: A phase 1 study

    Energy Technology Data Exchange (ETDEWEB)

    Lamki, L.M.; Buzdar, A.U.; Singletary, S.E.; Rosenblum, M.G.; Bhadkamkar, V.; Esparza, L.; Podoloff, D.A.; Zukiwski, A.; Hortobagyi, G.N.; Murray, J.L. (Department of Nuclear Medicine, University of Texas M.D. Anderson Cancer Center, Houston (USA))

    1991-07-01

    Sixteen patients with primary breast cancer were studied with a pancarcinoma monoclonal antibody B72.3, an IgG1 molecule directed against tumor-associated glycoprotein (TAG-72) present in several tumors. Five millicuries of 111In was used to label 0.2 mg (six patients), or 2 mg (six patients), or 20 mg using the site-directed bifunctional DTPA method (at carbohydrate moiety). Digital, planar, and SPECT images were obtained at 2, 48, 72 and 96 hr when possible. HAMA levels were obtained before the Mab infusion and at 1, 3, and 6 wk postinfusion. Fourteen of 14 known primary breast lesions were detected by imaging (100% sensitivity). Two fibrocystic lesions were negative. Seven of 14 patients had lymph node metastases by histologic methods, but all were missed by radioimmunoscintigraphy. Tumor uptake of Mab ranged 0.00054%-0.0038% of the ID/g. The tumor-to-normal breast tissue ratio was 4.3 {plus minus} 0.91 (mean {plus minus} s.e.m.). Lymph nodes localization of 111In-B72.3 by tissue analysis was similar for tumor-bearing and normal nodes (0.0039 {plus minus} 0.0023 versus 0.0025 {plus minus} 0.0019). Pharmacokinetics revealed mean plasma half-life of 33.3-41.2 hr for the different doses. There was no statistical difference between any of the pharmacokinetic parameters of different doses. HAMA was positive only in 17% of the patients. The study suggests that this antibody has 100% sensitivity for primary breast cancers, but very poor detection rate of metastatic lesions in axillary lymph nodes; thus making it of questionable value in the initial staging process of this disease.

  4. Scintigraphy with /sup 111/In-labeled antimyosin F(ab)/sub 2/ monoclonal antibody and /sup 99m/Tc-pyrophosphate in rhabdomyolysis

    Energy Technology Data Exchange (ETDEWEB)

    Krause, T.; Schuemichen, C.; Hohenloser, S.; Kasper, W.; Meinertz, T.

    1988-02-01

    A report is presented of the scintigraphic diagnosis of a generalized rhabdomyolysis with myocardial involvement using /sup 111/In labelled antimyosin F(ab)/sub 2/ monoclonal antibodies as compared to /sup 99m/Tc pyrophosphate.

  5. Use of isothiocyanatobenzyl-DTPA derivatized monoclonal antimyosin fab for enhanced in vivo target localization

    International Nuclear Information System (INIS)

    Khaw, B.A.; Gansow, O.; Brechbiel, M.W.; O'Donnell, S.M.; Nossiff, N.

    1990-01-01

    Monoclonal antimyosin Fab (AM-Fab) was radiolabeled with 111In via a new bifunctional chelating agent, isothiocyanatobenzyl-DTPA (SCN-DTPA), and used to visualize acute reperfused experimental myocardial infarction. Antibody localization was compared to 201 Tl (0.6 mCi) distribution in nine animals. Each animal was injected intravenously with 0.5 mCi of 111 In-SCN-DTPA AM-Fab preparations (Prep 1 [n = 5] and 2 [n = 4]). The biodistribution was compared to that of 111 In-labeled conventional bicyclic anhydride DTPA-AM-Fab (n = 5). 111 In-SCN-DTPA AM-Fab Prep 1 (lowest specific activity) showed highest specific target localization (31.6 +/- 3.5, MEAN infarct[0-20% Tl-201] to normal ration +/- SE) and lowest hepatic sequestration (0.0108 +/- 0.002% ID/g). Prep 2 showed similar infarct localization (18.4 +/- 1.2) to control 111 In-DTPA AM-Fab (16.9 +/- 1.1), but had higher hepatic activity (0.0326 +/- 0.014 and 0.0267 +/- 0.006 respectively). This difference in in vivo localization occurred despite the lack of changes in in vitro immunoreactivities of the AM-Fab preparations. The enhanced target localization with minimal hepatic activity may permit a more sensitive diagnostic application of 111 In-labeled AM-Fab in future clinical studies

  6. Indium 111 leucocyte scintigraphy in abdominal sepsis

    International Nuclear Information System (INIS)

    Baba, A.A.; McKillop, J.H.; Gray, H.W.; Cuthbert, G.F.; Neilson, W.; Anderson, J.R.

    1990-01-01

    We have studied the clinical utility of indium 111 autologous leucocyte scintigraphy retrospectively in 45 patients presenting with suspected intra-abdominal sepsis. The sensitivity was 95% (21/22) and the specificity was 91% (21/23). Some 34 of the studies (17 positive and 17 negative) were considered helpful in furthering patient management (76%) and 8, unhelpful (18%). In 3, the study results were misleading and led to inappropriate treatment. Indium 111 scintigraphy, whether positive or negative, provides information in patients with suspected intra-abdominal sepsis upon which therapeutic decisions can be based. (orig.)

  7. Synthesis of indium-111 mesoprotoporphyrin IX

    International Nuclear Information System (INIS)

    Lee, K.M.; Marshall, A.G.

    1981-01-01

    Indium-111 mesoprotoporphyrin IX has been prepared by refluxing suitable proportions of InCl 3 , sodium acetate, and mesoprotoporphyrin IX in glacial acetic acid. The labeled metalloporphyrin is sufficiently water-soluble for use as a scanning agent, and can also be incorporated into heme apoproteins for perturbed gamma-gamma angular correlation measurements. (author)

  8. Antimyosin imaging in cardiac transplant rejection

    International Nuclear Information System (INIS)

    Johnson, L.L.; Cannon, P.J.

    1991-01-01

    Fab fragments of antibodies specific for cardiac myosin have been labeled with indium-111 and injected intravenously into animals and into patients with heart transplants. The antibodies, developed by Khaw, Haber, and co-workers, localize in cardiac myocytes that have been damaged irreversibly by ischemia, myocarditis, or the rejection process. After clearance of the labeled antibody from the cardiac blood pool, planar imaging or single photon emission computed tomography is performed. Scintigrams reveal the uptake of the labeled antimyosin in areas of myocardium undergoing transplant rejection. In animal studies, the degree of antimyosin uptake appears to correlate significantly with the degree of rejection assessed at necropsy. In patients, the correlation between scans and pathologic findings from endomyocardial biopsy is not as good, possibly because of sampling error in the endomyocardial biopsy technique. The scan results at 1 year correlate with either late complications (positive) or benign course (negative). Current limitations of the method include slow blood clearance, long half-life of indium-111, and hepatic uptake. Overcoming these limitations represents a direction for current research. It is possible that from these efforts a noninvasive approach to the diagnosis and evaluation of cardiac transplantation may evolve that will decrease the number of endomyocardial biopsies required to evaluate rejection. This would be particularly useful in infants and children. 31 references

  9. Alterations in an indium-111 Fab' under conditions of utilization

    International Nuclear Information System (INIS)

    Halpern, S.E.; Sudora, E.; Tarburton, J.P.; Hagar, P.

    1992-01-01

    This study was conducted to investigate alterations that occur in an indium/111 Fab' of a monoclonal antibody following its in vivo administration. Patients were infused with 111 In-Fab' of the monoclonal antibody ZCE-025. Serum and urine specimens were collected from these pateients. Starting materials, serum, urine and controls samples were studied by electrophoresis. Animal distribution studies were performed in normal Balb/c mice and, in some cases, nude mice bearing a carcinoembryonic antigen (CEA)/producing human colon tumour since the antibody targets CEA. The studies indicated that the molecule circulated almost totally intact for at least 4 h and to a considerable extent for 24 h, with some evidence for in vivo fragmentation by 24 h. Evidence was also obtained suggesting the formation of a high molecular weight species in some patients. Shortly after infusion, some of the 111 In in the urine appeared as the intact Fab', but within hours the majority migrated electro-phoretically as low molecular weight species. We conclude that while the majority of the 111 In-Fab' of this particular antibody remains intact and immunoreactive following its administration, the molecule is structurally changed to some degree shortly after its infusion into humans. Since each monoclonal antibody is unique, the degree and rapidity of degradation of its Fab' in vivo could vary markedly from the above and possibly adversely effect its utility as a radiopharmaceutical. (orig.)

  10. Indium-111 platelet scintigraphy in carotid disease

    International Nuclear Information System (INIS)

    Branchereau, A.; Bernard, P.J.; Ciosi, G.; Bazan, M.; de Laforte, C.; Elias, A.; Bouvier, J.L.

    1988-01-01

    Forty-five patients (35 men, 10 women) undergoing carotid surgery had Indium-111 platelet scintigraphy as part of their preoperative work-up. Imaging was performed within three hours after injection of the Indium-111. A second series of views was obtained 24 hours later and repeated at 24 hour intervals for two days. Of 54 scintigrams, 22 were positive and 32 negative. Positive results were defined as a twofold or more increase in local activity on a visualized carotid after 24 hours. The sensitivity of the method was 41%, intraoperatively, and the specificity, 100%. The low sensitivity places this method behind sonography and duplex-scanning for screening patients for surgery. We believe that indications for platelet scintigraphy are limited to: 1. Repeated transient ischemic attacks in the same territory with minimal lesions on arteriography and non-homogeneous plaque on duplex scan; 2. Symptomatic patients being treated medically as a possible argument for surgery; 3. Determining therapeutic policy for patients having experienced a transient ischemic attack with a coexisting intracardiac thrombus

  11. Imaging of myocardial infarction in dogs and humans using monoclonal antibodies specific for human myosin heavy chains

    International Nuclear Information System (INIS)

    Leger, J.; Chevalier, J.; Larue, C.; Gautier, P.; Planchenault, J.; Aumaitre, E.; Messner, P.; Puech, P.; Saccavini, J.C.; Pau, B.

    1991-01-01

    The use of three different monoclonal antibodies specific for human ventricular myosin heavy chains in the visualization of the location and extent of necrosis in dogs with experimental acute myocardial infarction and in humans is described. Using a classic immunohistochemical method or ex vivo analysis of heart slices in dogs with acute myocardial infarction subjected to intravenous injection of unlabeled antimyosin antibodies or antimyosin antibodies labeled with indium-111, it was observed that all antibody fragments specifically reached the targeted necrotic zone less than 2 h after antibody injection and remained bound for up to 24 h. In a limited but significant number of cases (5 of the 12 humans and 11 of 43 dogs), it was possible to image the necrotic zone in vivo as early as 2 to 4 h after antibody injection. In other cases, individual blood clearance variations retarded or even prevented in vivo necrosis detection. Higher antimyosin fixation values were obtained in the necrotic zones in dogs with a rapid blood clearance relative to that of the other dogs. It is concluded that antimyosin antibodies always reached necrotic areas within 2 h. If blood clearance was rapid, in vivo imaging of the necrotic area was possible 2 to 6 h after necrosis, even in humans. In some cases, however, uncontrolled individual variations in the timing required for sufficient blood clearance hampered this rapid in vivo detection of myocardial necrosis

  12. Indium-111 leukocyte imaging in appendicitis

    International Nuclear Information System (INIS)

    Navarro, D.A.; Weber, P.M.; Kang, I.Y.; dos Remedios, L.V.; Jasko, I.A.; Sawicki, J.E.

    1987-01-01

    Indium- 111 -labeled leukocyte scintigraphy was applied to the diagnosis of acute appendicitis. Thirty-two patients observed in the hospital for possible appendicitis were prospectively studied. Scanning was done 2 hr after radiopharmaceutical injection. Thirteen scans were positive for acute appendicitis, and all but one were confirmed at laparotomy. In addition, two cases of colitis and two cases of peritonitis were detected. Of 15 negative studies, 11 had a benign course. Four patients with negative studies had laparotomy; two were found to have appendicitis and two had a normal appendix. Of 14 proven cases of appendicitis, 12 scans were positive for appendicitis with one false-positive scan, providing a sensitivity of 86%. Specificity was 93%: all negative cases except one had negative scans. Overall accuracy was 91% (29 of 32), comparing favorably with the accepted false-positive laparotomy rate of 25%. Use of In- 111 -labeled leukocyte scintigraphy serves to reduce the false-positive laparotomy rate and to shorten the clinical observation time in patients with acute appendicitis

  13. Indium-111 octreotide uptake in the surgical scar

    Energy Technology Data Exchange (ETDEWEB)

    Degirmenci, B.; Bekis, R.; Durak, H.; Derebeck, E. [Dokuz Eylul Univ., Izmir (Turkey). Dept. of Nuclear Medicine; Sen, M. [Dokuz Eylul Univ., Izmir (Turkey). Dept. of Radiation Oncology

    1999-07-01

    Indium-111 octreotide uptake has been reported in various somatostatin receptor positive tumors, granulomas and autoimmune diseases in which activated leucocytes may play a role, subcutaneous cavernous hemangioma and angiofibroma. We present Indium-111 octreotide uptake in a surgical abdominal scar tissue 1.5 to 6 months after surgery in a patient who had been treated for recurrent carcinoid tumor in the rectosigmoid junction. Indium-111 octreotide uptake in a surgical scar may be related to the binding to somatostatin receptors in the activated lymphocytes and fibroblasts that is previously reported. (orig.) [German] In verschiedenen Somatostatinrezeptor-positiven Tumoren, Granulomen, bei Autoimmunerkrankungen, in denen aktivierte Leukozyten eine Rolle spielen, subcutanen kavernoesen Hammangiomen und Angiofibromen wurde ueber die Anreicherung von Indium-111-Oktreotid berichtet. Wir berichten ueber die Anreicherung von Indium-111-Oktreotid in einer chirurgischen Narbe ueber dem Abdomen nach 1,5 und 6 Monaten bei einem Patienten mit einem Rezidiv-Karzinoid im rektosigmoidalen Uebergang. Die Anreicherung von Indium-111-Oktreotid in chirurgischen Narbengewebe koennte in Zusammenhang stehen mit einer Bindung an Somatostationrezeptoren in aktivierten Lymphozyten und Fibroblasten, ueber die schon berichtet wurde. (orig.)

  14. An optimized antibody-chelator conjugate for imaging of carcinoembryonic antigen with indium-111

    International Nuclear Information System (INIS)

    Sumerdon, G.A.; Rogers, P.E.; Lombardo, C.M.; Schnobrich, K.E.; Melvin, S.L.; Tribby, I.I.E.; Stroupe, S.D.; Johnson, D.K.; Hobart, E.D.

    1990-01-01

    A monoclonal antibody to carcinoembryonic antigen showing minimal cross-reactivity with blood cells and normal tissues was derivatized with benzylisothiocyanate derivatives of EDTA and DTPA. Seven chelators per immunoglobulin could be incorporated without loss of immunoreactivity. The resulting conjugates, labeled with indium-111, showed low liver uptake in animals. A cold kit, comprising the DTPA conjugate at a molarity of antibody bound chelator exceeding 1 x 10 -4 M, gave radiochemical yields of indium labeled antibody of ≥ 95% and was stable for 1 yr. (author)

  15. Diffuse pulmonary uptake of indium-111 chloride in idiopathic myelofibrosis

    International Nuclear Information System (INIS)

    Vieras, F.; Boyd, C.M.; Mora, P.A.

    1979-01-01

    Unusual indium-111 accumulation and extramedullary hematopoiesis in the lungs of a patient with idiopathic myelofibrosis are described. The bone marrow scan taken 24 h after intravenous injection of 111 InCl 3 faithfully depicted the abnormal distribution of marrow elements as assessed histologically at autopsy, thereby supporting the usefulness of 111 InCl 3 for marrow imaging

  16. Indium 111 WBC scan in local and systemic fungal infections

    International Nuclear Information System (INIS)

    Haseman, M.K.; Blake, K.; McDougall, I.R.

    1984-01-01

    We describe two patients-one with a systemic fungal infection and one with a localized form-who had strikingly abnormal indium 111 leukocyte (WBC) scans. The patient with systemic disease had an abnormal WBC scan before lesions became clinically apparent

  17. Current status of indium-111 labeled bleomycin for tumor detection

    International Nuclear Information System (INIS)

    Taylor, R.D.; Blahd, W.H.

    1975-01-01

    The advantages and disadvantages of 111 In-labeled bleomycin for tumor detection are briefly mentioned. Indium-111 labeled bleomycin does localize in human tumors. However, its role in tumor detection and staging as compared with 67 Ga is still somewhat controversial

  18. Antimyosin scintigraphy in patients with acquired and hereditary muscular disorders

    International Nuclear Information System (INIS)

    Loefberg, M.; Liewendahl, K.; Savolainen, S.; Nikkinen, P.; Lamminen, A.; Tiula, E.; Somer, H.

    1994-01-01

    Scintigraphy with indium-111 labelled antimyosin has an established role in the evaluation of cardiac muscle damage. This antibody has been shown to cross-react with myosin in skeletal muscle. We therefore studied the usefulness of this method for the detection of skeletal muscle lesions in rhabdomyolysis, myositis and hereditary muscular dystrophies. All nine patients with rhabdomyolysis had focal uptake of antimyosin antibody which correlated with the clinical findings of soft tissue damage. However, a number of symptomless lesions were also detected by immunoscintigraphy. In rhabdomyolysis the target to non-target uptake ratios varied from 1.3 to 7.6. Diffuse uptake of antibody in skeletal muscle was observed in all three patients with polymyositis-dermatomyositis and in 12 out of 13 patients with muscular dystrophies. In myositis the intensity of antibody accumulation correlated reasonably well with the magnitude of oedema detected by magnetic resonance imaging (MRI). Most patients with Becker type or non-X-chromosomal muscular dystrophies showed slight or moderate uptake of antibody, mainly in the lower extremities. In these patients more antibody accumulated in the calves than in the thighs, whereas the findings on MRI were more prominent in the thighs than in the calves, presumably because of the better preserved muscle bulk in the calves. We conclude that antimyosin scintigraphy can be used for the detection of muscle lesions not only in acquired muscle diseases but also in hereditary muscular disorders, and that immunoscintigraphy provides information on muscle disease activity not obtainable with MRI. (orig.)

  19. Antimyosin scintigraphy in patients with acquired and hereditary muscular disorders

    Energy Technology Data Exchange (ETDEWEB)

    Loefberg, M. (Dept. of Neurology, Helsinki Univ. Central Hospital (Finland)); Liewendahl, K. (Dept. of Clinical Chemistry, Helsinki Univ. Central Hospital (Finland)); Savolainen, S. (Dept. of Clinical Chemistry, Helsinki Univ. Central Hospital (Finland)); Nikkinen, P. (Dept. of Clinical Chemistry, Helsinki Univ. Central Hospital (Finland)); Lamminen, A. (Dept. of Radiology, Helsinki Univ. Central Hospital (Finland)); Tiula, E. (First Dept. of Internal Medicine, Helsinki Univ. Central Hospital (Finland)); Somer, H. (Dept. of Neurology, Helsinki Univ. Central Hospital (Finland))

    1994-10-01

    Scintigraphy with indium-111 labelled antimyosin has an established role in the evaluation of cardiac muscle damage. This antibody has been shown to cross-react with myosin in skeletal muscle. We therefore studied the usefulness of this method for the detection of skeletal muscle lesions in rhabdomyolysis, myositis and hereditary muscular dystrophies. All nine patients with rhabdomyolysis had focal uptake of antimyosin antibody which correlated with the clinical findings of soft tissue damage. However, a number of symptomless lesions were also detected by immunoscintigraphy. In rhabdomyolysis the target to non-target uptake ratios varied from 1.3 to 7.6. Diffuse uptake of antibody in skeletal muscle was observed in all three patients with polymyositis-dermatomyositis and in 12 out of 13 patients with muscular dystrophies. In myositis the intensity of antibody accumulation correlated reasonably well with the magnitude of oedema detected by magnetic resonance imaging (MRI). Most patients with Becker type or non-X-chromosomal muscular dystrophies showed slight or moderate uptake of antibody, mainly in the lower extremities. In these patients more antibody accumulated in the calves than in the thighs, whereas the findings on MRI were more prominent in the thighs than in the calves, presumably because of the better preserved muscle bulk in the calves. We conclude that antimyosin scintigraphy can be used for the detection of muscle lesions not only in acquired muscle diseases but also in hereditary muscular disorders, and that immunoscintigraphy provides information on muscle disease activity not obtainable with MRI. (orig.)

  20. Indium 111 ZCE-025 immunoscintigraphy in occult recurrent colorectal cancer with elevated carcinoembryonic antigen level

    International Nuclear Information System (INIS)

    Doerr, R.J.; Abdel-Nabi, H.; Merchant, B.

    1990-01-01

    We investigated the utility of scanning with indium 111 labeled to monoclonal antibody in 13 patients after curative resection of colorectal cancer who had elevated carcinoembryonic antigen levels and negative results of clinical workup. Each patient received 1 mg of anti-carcinoembryonic antigen monoclonal antibody type ZCE 025 labeled with 5.5 mCi of 111 In, plus 9 to 39 mg of the same antibody unlabeled. Patients underwent scanning 3 to 7 days after infusion by planar and emission computed tomography. ZCE-025 monoclonal antibody imaging detected tumor recurrence or metastasis in 11 of 13 patients. In one patient the monoclonal antibody scan gave a true-negative result, and in one patient the monoclonal antibody scan failed to disclose a metachronous cecal primary. Tumor sites identified were the pelvis (2 patients), abdominal wall (2), retroperitoneum (1), lymph nodes (3); liver (2), bone (2), and lung (1). The accurate localization of colorectal carcinoma recurrences by means of 111 In ZCE-025 monoclonal antibody demonstrates the usefulness of this diagnostic agent in the setting of elevated carcinoembryonic antigen level and negative results of clinical and radiologic workup

  1. Clinical evaluation of the platelet scintigraphy using indium-111 oxine

    International Nuclear Information System (INIS)

    Ishikawa, Nobuyoshi; Takeda, Tohoru; Nakajima, Kohtaroh; Satoh, Motohiro; Akisada, Masayoshi; Ijima, Hiroshi

    1988-01-01

    The clinical usefulness of autologous platelets labeled with Indium-111 oxine was evaluated by scintigraphy as a diagnostic procedure for the detection of various thrombotic disorders as well as in different aneurysms. The positivity was found to be satisfactory (80.0 %) in cases of aortic aneurysm while thoracic aneurysm showed comparatively poor accumulation. High positivity was also demonstrated in deep vein thrombosis. The complimentary role of this method for intracardiac thrombi to echocardiography was noted. The labeling procedure of indium-111 oxine was fairly easy to perform and the activity of labeled platelets was sustained enough to yield good results. In one case scintigraphy was performed successfully after 19 hours of angiography when a hot area of labeled platelets was seen at the puncture site. This method was therefore varified to be a sensitive and reliable method in the assessment of thrombus activity, and as it demonstrates the activity, its helpfulness in the conservative treatment of these disorders is warranted. (author)

  2. Indium-111-labelled leucocytes for localisation of abscesses

    International Nuclear Information System (INIS)

    Segal, A.W.; Thakur, M.L.; Arnot, R.N.; Lavender, J.P.

    1976-01-01

    Leucocytes from eight patients who were thought to have an abscess were labelled with indium-111 and reintroduced into the circulation. The distribution of radioactivity was followed by whole-body scanning and imaging with a gamma camera. Focal accumulations of radioactivity were observed in the lesion in the three patients with abscesses, in the lungs of a boy with bacterial endocarditis, in the knee of a woman with rheumatoid arthritis, and at the site of intramuscular injections in another patient. The use of radiolabelled cells for the detection of focal pathological processes would seem to be an important addition to conventional diagnostic methods. (author)

  3. Indium-111-labelled leucocytes for localisation of abscesses

    Energy Technology Data Exchange (ETDEWEB)

    Segal, A W; Thakur, M L; Arnot, R N; Lavender, J P [Royal Postgraduate Medical School, London (UK)

    1976-11-13

    Leucocytes from eight patients who were thought to have an abscess were labelled with indium-111 and reintroduced into the circulation. The distribution of radioactivity was followed by whole-body scanning and imaging with a gamma camera. Focal accumulations of radioactivity were observed in the lesion in the three patients with abscesses, in the lungs of a boy with bacterial endocarditis, in the knee of a woman with rheumatoid arthritis, and at the site of intramuscular injections in another patient. The use of radiolabelled cells for the detection of focal pathological processes would seem to be an important addition to conventional diagnostic methods.

  4. Indium-111 oxine labelling of white blood cells

    International Nuclear Information System (INIS)

    Lavender, J.P.; Silvester, D.J.; Goldman, J.; Hammersmith Hospital, London

    1978-01-01

    Following work done by Professor John McAfee and Mathew Thakur at the MRS Cyclotron Unit a method is available for labelling cells with indium-111 which results in a stable intracellular marker. The method uses indium-111-8 hydroxyquinoline (111In oxine) which is a lipoid soluble complex which goes across the cell membrane and results in the deposition of indium into various subcellular structures. It has been applied to various preparations of white cells, platelets and also malignant cells. Autologous granulocytes have been used to identify inflammatory lesions in 35 patients. By similar means autologous lymphocytes can also be labelled and reinfused. Lymphocytes have been shown in animals to circulate from the blood via the lymphatic system and then returning to the blood once more. The same phenomenon can be seen in man using indium labelled lymphocytes. Lymph nodes become visible at between 12 and 18 hours and recirculation of labelled cells can be shown on the blood activity curves. Certain problems arise concerning cell behaviour after labelling which appear due to irradiation of cells rather than chemical toxicity. (author)

  5. Preparation of human cardiac anti-myosin: a review

    International Nuclear Information System (INIS)

    Okada, H.; Souza, I.T.T.

    1990-01-01

    The present communication is a review of the physicochemical characterization and immunological properties of myosin isolated from the cardiac muscle, the production of monoclonal antibody anti-myosin, the radiolabeling of this antibody and its applications as radiopharmaceuticals to imaging myocardial infarcts. The classical example of radioimmunologic diagnosis of non malignant tissues is the detection of myocardial infarction by radiolabeled antibodies to myosin. (author)

  6. Quantitative Assessment of Myocardial Infarction by In-111 Antimyosin Antibody

    Energy Technology Data Exchange (ETDEWEB)

    Lee, Myung Chul; Lee, Kyung Han; Choi, Yoon Ho; Chung, June Key; Park, Young Bae; Koh, Chang Soon [Seoul National University College of Medicine, Seoul (Korea, Republic of); Moon, Dae Hyuk [Asan Medical Center, Ulsan University College of Medicine, Seoul (Korea, Republic of)

    1991-03-15

    Infarct size is a major determinant of prognosis after acute myocardial infarction. Up to date, however, clinically available tests to estimate this size have not been sufficiently accurate. Twelve lead electrocardiogram and wall motion abnormality measurement are not quantitative, and creatine phosphokinase (CPK) measurement is inaccurate in the presence of reperfusion or right ventricular infarction. Methods have been developed to localize and size acute myocardial infarcts with agents that are selectively sequestered in areas of myocardial damage, but previously used agents have lacked sufficient specificity. Antibodies that bind specifically only to damaged myocardial cells may resolve this problem and provide an accurate method for noninvasively measuring infarct size. We determined the accuracy with which infarcted myocardial mass can be measured using single photon emission computed tomography (SPECT) and radiolabeled antimyosin antibodies. Seven patients with acute myocardial infarction and one stable angina patient were injected with 2 mCi of Indium-111 labeled antimyosin antibodies. Planar image and SPECT was performed 24 hours later. None of the patients had history of prior infarcts, and none had undergone reperfusion techniques prior to the study, which was done within 4 days of the attack. Planar image showed all infarct patients to have positive uptakes in the cardiac region. The location of this uptake correlated to the infarct site as indicated by electrocardiography in most of the cases. The angina patient, however, showed no such abnormal uptake. Infarct size was determined from transverse slices of the SPECT image using a 45% threshold value obtained from a phantom study. Measured infarct size ranged from 40 to 192 gr. There was significant correlation between the infarct size measured by SPECT and that estimated from serial measurements of CPK (r=0.73, p<0,05). These date suggest that acute myocardial infarct size can be accurately measured

  7. Indium-111 tropolone, a new tracer for platelet labeling

    International Nuclear Information System (INIS)

    Dewanjee, M.K.; Rao, S.A.; Rosemark, J.A.; Chowdhury, S.; Didisheim, P.

    1982-01-01

    Platelets have been labeled with a new neutral, lipid-soluble metal complex of indium 111 ( 111 In) and tropolone. Unlike oxine, which is soluble in ethyl alcohol, tropolone is soluble in isotonic saline. Platelet labeling with 111 In tropolone can be performed in both acid-citrate-dextrose (ACD) plasma and ACD saline within two hours. Labeling efficiency has been 80% to 90%. 111 In tropolone in ACD saline and ACD plasma at tropolone concentrations of 5 and 10 micrograms/ml, respectively, and incubation of the platelets with the tracer at room temperature for 20 minutes were optimal conditions for labeling. The authors have developed an ACD-saline kit for convenient preparation of 111 In-labeled platelets. No adverse effect of 111 In tropolone on platelets has been observed in studies of biodistribution, recovery, and survival of platelets in rabbits and dogs

  8. Indium-111 tropolone, a new tracer for platelet labeling

    International Nuclear Information System (INIS)

    Dewanjee, M.K.; Rao, S.A.; Rosemark, J.A.; Chowdhury, S.; Didisheim, P.

    1982-01-01

    Platelets have been labeled with a new neutral, lipid-soluble metal complex of indium 111 ( 111 In) and tropolone. Unlike oxine, which is soluble in ethyl alcohol, tropolone is soluble in isotonic saline. Platelet labeling with 111 In tropolone can be performed in both acid-citrate-dextrose (ACD) plasma and ACD saline within two hours. Labeling efficiency has been 80% to 90%. 111 In tropolone in ACD saline and ACD plasma at tropolone concentrations of 5 to 10 μg/ml, respectively, and incubation of the platelets with the tracer at room temperature for 20 minutes were optimal conditions for labeling. The authors have developed an ACD-saline kit for convenient preparation of 111 In-labeled platelets. No adverse effect of 111 In tropolone on platelets has been observed in studies of biodistribution, recovery, and survival of platelets in rabbits and dogs

  9. False positive indium-111 white blood cell scan in a closed clavicle fracture

    International Nuclear Information System (INIS)

    Friedman, R.J.; Gordon, L.

    1988-01-01

    Aggressive treatment of the multiply injured patient often requires early fixation of many fractures, some of which may be open. Often, patients develop postoperative fevers requiring a thorough workup to rule out infection. Recently, indium-111 white blood cell (WBC) imaging has become a valuable adjunct in the diagnosis of acute infection. The patient described had a simple, closed clavicle fracture with markedly increased activity on an indium-111 WBC scan obtained for fever workup. This subsequently proved to be a normal, healing, noninfected fracture by other diagnostic techniques. Noninfected, simple closed fractures should be added to the list of causes for a false-positive indium-111 WBC scan

  10. Distribution and dosimetry of indium-111 labeled F(ab')2 fragments in humans

    International Nuclear Information System (INIS)

    Doherty, P.; Schwinger, R.; King, M.; Gionet, M.

    1986-01-01

    The purpose of this study was to obtain quantitative biodistribution data in patients injected with the indium-111 labeled F(ab') 2 fragments of mouse monoclonal antibody. From this data dosimetric calculations were made for the individual organs. The authors also evaluated the quantitative properties of SPECT in this application and compared it with the more conventional two view planar technique in both phantom and patient studies. For one antibody (19-9) the mean dose in rads/mCi for the organs of highest accumulation, namely, the liver and kidneys was 3.2 and 2.6 respectively. Preliminary data from another antibody (OC 125) showed much higher blood levels and a significantly lower liver dose of 2.3 indicating that antibody type is another significant determinant in dosimetry. The SPECT approach particularly in the presence of background activity, was more accurate in the phantom studies and resulted in larger estimated doses in the patient studies. Also, SPECT has the added advantage of providing an index of organ volume, which has to be balanced with the fact the planar is more rapid, and does not require special hardware. 24 references, 5 figures, 1 table

  11. Detection of a prosthetic aortic valvular abscess with indium-111-labeled leukocytes

    Energy Technology Data Exchange (ETDEWEB)

    Oates, E.; Sarno, R.C.

    1988-10-01

    An unsuspected annular abscess at the base of a prosthetic aortic valve in a patient with endocarditis was identified by indium-111-labeled leukocyte scintigraphy alone. This highly sensitive and specific technique expediently demonstrated the surgically proven inflammatory focus.

  12. Detection of a prosthetic aortic valvular abscess with indium-111-labeled leukocytes

    International Nuclear Information System (INIS)

    Oates, E.; Sarno, R.C.

    1988-01-01

    An unsuspected annular abscess at the base of a prosthetic aortic valve in a patient with endocarditis was identified by indium-111-labeled leukocyte scintigraphy alone. This highly sensitive and specific technique expediently demonstrated the surgically proven inflammatory focus

  13. Evaluation of indium-111 colloid for radionuclide imaging of the abdominal lymph nodes

    International Nuclear Information System (INIS)

    Vieras, F.; Hamilton, R.F.; Grissom, M.P.; Kiepffer, R.F.; Vandergrift, J.F.

    1981-01-01

    The experimental evaluation of indium-111 colloid for imaging the para-aortic lymph nodes in animals is described and preliminary results obtained in human subjects. Serial lymphatic scintigraphy performed in beagle dogs following bilateral pedal subcutaneous injections of indium-111 colloid revealed good para-aortic lymph node visualization. A normal migration pattern of indium-111 colloid was also observed in human subjects following subcutaneous injection in the feet; there was clear visualization of the ileo-inguinal and para-aortic lymph nodes. Organ distribution studies for indium-111 colloid were performed in rats following unilateral pedal subcutaneous injection in rats; these results were used for calculating radiation dose estimates to various organs. The study demonstrates the feasibility of using 111 In-colloid clinically for abdominal lymphatic scintiography for the use of sup(99m)Tc-labelled colloids results in lower radiation doses. (U.K.)

  14. Imaging experimental coronary artery thrombosis with indium-111 platelets

    International Nuclear Information System (INIS)

    Riba, A.L.; Thakur, M.L.; Gottschalk, A.; Zaret, B.L.

    1979-01-01

    The ability of cardiac scintigraphy with indium-111 ( 111 In)-labeled platelets to detect coronary artery thrombosis (CAT) was assessed in a canine model. Cardiac imaging and tissue distribution studies were performed shortly after administering 111 In-labeled platelets to 12 dogs (group 1) with acute CAT. Four dogs (group 2) with acute CAT were studied 2 and 22 hours after administering 111 In platelets. In addition, four dogs (group 3) with 24-hour-old CAT were similarly evaluated. In all group 1 animals, in vivo imaging 1 to 2 hours after 111 In platelet administration revealed intense uptake in the region of thrombus-containing left anterior descending arteries that was readily discernible from background blood pool activity. Sequential imaging of the four group 2 animals over a 22-hour period revealed no change in the scintigraphic pattern of the thrombosed arteries. In contrast, 111 In platelet imaging in the four group 3 animals with 24-hour-old CAT failed to reveal enhanced activity within the region of the thrombus-containing coronary artery. In the 12 group 1 animals, the CAT accumulated 69 +- 10 (mean +- SEM) times greater activity than present in blood and 651 +- 135 times greater activity than normal left ventricular myocardium. There was 24 +- 7 times greater 111 In activity in the damaged left anterior descending arteries compared with normal circumflex arteries. Similar uptake ratios were seen in group 2 animals. The 24-hour old thrombi from group 3 animals showed no enhanced 111 In uptake. This study demonstrates that experimental acute CAT can be detected readily with 111 In platelet cardiac scintigraphy

  15. 111indium-antimyosin immunoscintigraphy in suspected myocarditis

    International Nuclear Information System (INIS)

    Krause, T.; Schuemichen, C.; Joseph, A.; Moser, E.; Zeiher, A.

    1991-01-01

    111 Indium-monoclonal antimyosin scans were carried out in 21 patients with suspected myocarditis, confirmed by reduced ejection volume, pericardial effusion and clinical follow up in 12 patients. Coronary heart disease was excluded angiographically in all cases. Quantitative evaluation of myocardial 111 In-antimyosin accumulation 48 hours after injection showed a pathological uptake in 10/12 patients with increased heart/lung ratios (Q 48 >1,58). Ratios were also elevated in 2 patients with cardiomyopathy, 2 suffering from vasculitis and 1 with dermatomyositis. Four patients without proven cardiac disease had normal ratios (Q 48 ≤1,58). Examination after 24 hours was of limited value, depending on the residual blood pool activity. Visual analysis of the scans showed a high interobserver variation despite a positive correlation with quantitative analysis (48 h p.i.: r=0,72; p 111 In-antimyosin scan as a screening method prior to myocardial biopsy. However, scintigraphy cannot definitely elucidate the cause of myocardial damage. Therefore, myocardial biopsy is still recommended after positive antimyosin scans. (orig.) [de

  16. Pharmacokinetics of chimeric L6 conjugated to indium-111- and yttrium-90-DOTA-peptide in tumor-bearing mice

    International Nuclear Information System (INIS)

    DeNardo, S.J.; Zhong, G.R.; Salako, Q.

    1995-01-01

    A bifunctional chelating agent, DOTA-Gly 3 -L-(p-isothiocyanato)-phenylalanine amide (DOTA-peptide-NCS), was studied in nude mice bearing human breast cancer xenografts (HBT 3477) to determine its potential for radioimmunoconjugate therapy. Indium-111 and yttrium-90 were attached to an anti-adenocarcinoma chimeric L6 (ChL6) monoclonal antibody (MAb) after pre-chelation to the DOTA-peptide-NCS and the desired neutral radiochelates were obtained by purification. The unique characteristic of the DOTA-peptide-NCS to form neutral complexes with trivalent metals was utilized to separate the resulting 111 In and 90 Y radiochelates from excess chelating agent and other anionic by-products resulting from metal impurities. The purified radiochelates were then conjugated to ChL6. The paramacokinetics of 111 In- and 90 Y-DOTA-peptide-ChL6 were obtained for 5 days after injection in nude mice bearing HBT 3477 xenographs. The results were compared with the pharmacokinetics of 125 I-ChL6 obtained in the same mouse model. The whole-body clearance of 125 I-ChL6, 90 Y-and 111 In-DOTA-peptide-ChL6 was monoexponential with biologic half-times of 92, 104 and 160 hr, respectively. Blood clearances of the three radiopharmaceuticals were biphasic. The radiometal immunoconjugates had greater tumor uptake and slower clearances. Indium-111- and 90 Y-DOTA-peptide-ChL6 can be produced at high specific activity with fewer than one chelate per MAb by using a pre-labeling method that permits radiochelate purification by charge selection. Studies in mouse xenografts indicate that tumor uptake in enhanced and a favorable therapeutic index is achieved using these agents. 29 refs., 7 figs., 2 tabs

  17. Evaluation of musculoskeletal sepsis with indium-111 white blood cell imaging

    International Nuclear Information System (INIS)

    Ouzounian, T.J.; Thompson, L.; Grogan, T.J.; Webber, M.M.; Amstutz, H.C.

    1987-01-01

    The detection of musculoskeletal sepsis, especially following joint replacement, continues to be a challenging problem. Often, even with invasive diagnostic evaluation, the diagnosis of infection remains uncertain. This is a report on the first 55 Indium-111 white blood cell (WBC) images performed in 39 patients for the evaluation of musculoskeletal sepsis. There were 40 negative and 15 positive Indium-111 WBC images. These were correlated with operative culture and tissue pathology, aspiration culture, and clinical findings. Thirty-eight images were performed for the evaluation of possible total joint sepsis (8 positive and 30 negative images); 17 for the evaluation of nonarthroplasty-related musculoskeletal sepsis (7 positive and 10 negative images). Overall, there were 13 true-positive, 39 true-negative, two false-positive, and one false-negative images. Indium-111 WBC imaging is a sensitive and specific means of evaluating musculoskeletal sepsis, especially following total joint replacement

  18. Work in progress: radionuclide imaging of indium-111-labeled eosinophils in mice

    International Nuclear Information System (INIS)

    Runge, V.M.; Rand, T.H.; Clanton, J.A.; Jones, J.P.; Colley, D.G.; Partain, C.L.; James, A.E. Jr.

    1983-01-01

    Eosinophils isolated from peritoneal exudates were labeled with indium-111-oxine and injected intravenously into sensitized mice. They became localized at sites of inflammation produced by intradermal injections of schistosomal antigen or Toxocara canis larvae, whereas labeled neutrophils did not. Intense uptake of eosinophils by normal spleen, liver, and bone marrow was noted, with tracer distribution effectively complete by 5 hours after injection. Indium-111-eosinophil studies appear to be quite sensitive to parasitic inflammatory reactions; in contrast, nonspecific inflammation such as that induced by turpentine causes localization of eosinophils, but to a lesser extent. This technique may be useful in the study of parasitic and allergic disease

  19. Use of indium-111-labeled white blood cells in the diagnosis of diabetic foot infections

    International Nuclear Information System (INIS)

    Zeiger, L.S.; Fox, I.M.

    1990-01-01

    The diagnosis of bone infection in the patient with nonvirgin bone is a diagnostic dilemma. This is especially true in the diabetic patient with a soft tissue infection and an underlying osteoarthropathy. The authors present a retrospective study using the new scintigraphic technique of indium-111-labeled white blood cells as a method of attempting to solve this diagnostic dilemma

  20. The clinical utility of indium-111 labelled platelet scintigraphy in the diagnoses of renal transplant rejection

    International Nuclear Information System (INIS)

    Desir, G.V.; Bia, M.; Lange, R.C.; Smith, E.O.; Flye, W.; Kashgarian, M.; Schiff, M.; Ezekowitz, M.D.

    1990-01-01

    It is demonstrated that indium-111 labelled platelet scintigraphy is a highly accurate test for detecting acute untreated renal allograft rejection and it is shown that changes in platelet uptake can precede signs and symptoms of rejection by at least 48 hours. (author). 34 refs.; 2 figs.; 1 tab

  1. Modified method for labeling human platelets with indium-111 oxine using albumin density-gradient separation

    International Nuclear Information System (INIS)

    Bunting, R.W.; Callahan, R.J.; Finkelstein, S.; Lees, R.S.; Strauss, H.W.

    1982-01-01

    When labeling platelets with indium-111 oxine, albumin density-gradient separation minimizes the time spent to resuspend those platelets that have been centrifuged against a hard surface. Labeling efficiency or platelet viability, as measured by platelet survival or aggregation with adenosine diphosphate, are not adversely affected

  2. Study of the cerebro-spinal fluid circulation indium 111 labelled DTPA. Report of 300 cases

    International Nuclear Information System (INIS)

    Moreau, R.; Askienazy, S.; Mathieu, E.; Moretti, J.-L.

    1976-01-01

    A study of the C.S.F. circulation by intrathecal injection of radioactive tracers is a usual technique of neurological exploration. Indium-111 DTPA has numerous advantages for this type of study. It is a chelating agent, the renal clearance of which is rapid and which has no toxicity at the dose injected. Indium-111 is a cyclotron product with a half-life (2.8 days) compatible with the duration of the examination. Finally the dose of radioactivity delivered by this isotope is less than that of iodine 131, Technetium 99m, and ytterbium 169. In normal subjects after injection by the lumbar route, the average biological half-life measured by external counting lies between 20 and 28 hours. A study of the circulation of the C.S.F. is particularly useful in patients suspected of hydrocephalus. It permits finer diagnosis and shows the indication and type of by pass operation that may be necessary. An increase in the biological half-life of indium 111-DTPA seems to be a good indication for such an operation. An experience of 300 patients has shown the interest of the use of Indium 111-DTPA which now seems to be the best radio-isotope for the study of the subarachnoid space [fr

  3. Indium-111 labelled leucocyte scintigraphy in the diagnosis of inflammatory disease

    International Nuclear Information System (INIS)

    Roevekamp, M.H.

    1982-01-01

    The purpose of this study was to evaluate the diagnostic usefulness of indium-111 oxinate labelled autologous leucocytes in inflammatory disease. Chapter I provides an outline of the theoretical aspects of leucocyte labelling with indium-111 oxinate, as well as giving a description of the labelling method and scintigraphic technique and of the in-vitro and in-vivo studies performed to evaluate the method. In Chapter II details are given of the initial results obtained in a pilot study. A high false-negative rate led to modification of the labelling technique. The results obtained in patients suspected of intra-abdominal or retroperitoneal located inflammatory lesions are described in Chapter III. Chapter IV contains the description of an indium-111-leucocyte-99mTc-Sn-colloid computer-assisted subtraction technique for a better evaluation of patients suspected of an upper-abdominal inflammatory process. In Chapter V the study performed in patients after arterial reconstructive surgery is described, and the results obtained in patients suspected of an infected orthopaedic prosthesis are given in Chapter VI. Finally the characteristics of the different types of inflammatory responses is reviewed. (Auth.)

  4. Ultrasonography and indium 111 white blood cell scanning for the detection of intraabdominal abscesses

    International Nuclear Information System (INIS)

    Carroll, B.; Silverman, P.M.; Goodwin, D.A.; McDougall, I.R.

    1981-01-01

    Ultrasound and indium 111 white blood cell scanning were performed on 163 patients with suspected intraabdominal abscesses. In all but one case, intraabdominal abscesses were correctly identified by one or both tests; conversely, no patient was falsely diagnosed by both tests to have an abscess. Sonography was useful in those patients with focal symptoms, and frequently identified nonabscess causes for fever. White cell scanning was valuable when focal signs were absent, and frequently identified extraabdominal sources of sepsis. The two imaging modalities are complementary and provide a highly accurate and sensitive means of intraabdominal abscess detection

  5. Usefulness of bone marrow magnetic resonance imaging and indium-111-chloride bone marrow scintigraphy in patients with various hematological diseases

    Energy Technology Data Exchange (ETDEWEB)

    Kobayashi, Yutaka; Umekawa, Tsunekazu; Chikayama, Satoshi [Osaka General Hospital of West Japan Railway Compapy (Japan)] [and others

    1995-03-01

    This study investigated the ability of magnetic resonance (MR) imaging and indium-111 chloride (In-111) scintigraphy to assess bone marrow in various hematological lesions. The subjects were 7 with aplastic anemia (AA), 4 with myelodysplastic syndrome (MDS), 3 with polycythemia (PC), 3 with essential thrombocythemia (ET), 2 with multiple myeloma (MM), 2 with monoclonal gammopathy of undetermined significance (MGUS), 3 with idiopathic thrombocytopenic purpura (ITP), one with acute lymphocytic leukemia (ALL), and one with secondary anemia due to chronic inflammation (SA). Bone marrow cellularity was assessed on MR images and both uptake and tissue distribution were assessed on In-111 scintigraphy. Hypo-cellularity was seen in all AA patients, but not seen in any other patient in each group. On the other hand, hyper-cellularity was seen in 3 MDS, one PC, all 3 ET, one ALL, and one SA patients. In the group of MM, the vertebral body was seen as heterogenous signal intensity on MR images. Bone marrow was seen as iso-intensity in one MDS, 2 PC, all 2 MGUS, and all 3 ITP patients. In-111 scintigraphy showed decrease or disappearance of tracer uptake and decreased tissue distribution in all 7 AA, one MDS, one PC, and one ALL patients. Increased tracer uptake and enlarged tissue distribution were seen in one MDS, one PC, and one SA patients. One MDS, one ET, all 2 MM, all 2 MGUS, all 3 ITP patients had tracer uptake and tissue distribution that were equal to those in the normal tissues. Since MR imaging and In-111 scintigraphy provided qualitatively different information, the combination of both modalities would contribute to the understanding of bone marrow condition in hematopoietic diseases. (N.K.).

  6. Synthesis, characterization and theranostic evaluation of Indium-111 labeled multifunctional superparamagnetic iron oxide nanoparticles

    International Nuclear Information System (INIS)

    Zolata, Hamidreza; Abbasi Davani, Fereydoun; Afarideh, Hossein

    2015-01-01

    Indium-111 labeled, Trastuzumab-Doxorubicin Conjugated, and APTES-PEG coated magnetic nanoparticles were designed for tumor targeting, drug delivery, controlled drug release, and dual-modal tumor imaging. Superparamagnetic iron oxide nanoparticles (SPIONs) were synthesized by thermal decomposition method to obtain narrow size particles. To increase SPIONs circulation time in blood and decrease its cytotoxicity in healthy tissues, SPIONs surface was modified with 3-Aminopropyltriethoxy Silane (APTES) and then were functionalized with N-Hydroxysuccinimide (NHS) ester of Polyethylene Glycol Maleimide (NHS-PEG-Mal) to conjugate with thiolated 3,6,9,15-tetraazabicyclo[9.3.1]pentadeca-1(15),11,13-triene-3,6, 9,-triacetic acid (PCTA) bifunctional chelator (BFC) and Trastuzumab antibody. In order to tumor SPECT/MR imaging, SPIONs were labeled with Indium-111 (T 1/2 = 2.80d). NHS ester of monoethyl malonate (MEM-NHS) was used for conjugation of Doxorubicin (DOX) chemotherapeutic agent onto SPIONs surface. Mono-Ethyl Malonate allows DOX molecules to be attached to SPIONs via pH-sensitive hydrazone bonds which lead to controlled drug release in tumor region. Active and passive tumor targeting were achieved through incorporated anti-HER2 (Trastuzumab) antibody and EPR effect of solid tumors for nanoparticles respectively. In addition to in vitro assessments of modified SPIONs in SKBR3 cell lines, their theranostic effects were evaluated in HER2 + breast tumor bearing BALB/c mice via biodistribution study, dual-modal molecular imaging and tumor diameter measurements

  7. Bone-marrow imaging with indium-111 chloride in aplastic anemia and myelofibrosis: concise communication

    International Nuclear Information System (INIS)

    Sayle, B.A.; Helmer, R.E.; Birdsong, B.A.; Balachandran, S.; Gardner, F.H.

    1982-01-01

    Twenty-nine patients with aplastic anemia and 11 patients with myelofibrosis were evaluated with indium-111 chloride bone-marrow imaging, ferrokinetics, and bone-marrow core biopsies. There was good correlation between the erythrocyte cellularity of the marrow and the In-111 bone-marrow scan grades in most patients. In some, the overall scan grade tended to underestimate the erythroid elements because the core biopsy had been taken from the area of the greatest radionuclide concentration on the scan. In patients with aplastic anemia, there was good correlation between the plasma iron clearance t1/2 and the scan grade. Less agreement was found in the comparison between the Fe-59 sacral and organ counts and the red-cell iron utilization. In patients with myelofibrosis, there was poor correlation between the surface counts over the sacrum and the red-cell iron utilization. Plasma iron clearances were abnormally short and were unrelated to the transferrin saturation levels. Eighteen patients were studied several times to evaluate their responses to steroid therapy. In all, there was good correlation between the bone-marrow imaging, the erythrocyte cellularity, ferrokinetics, and the patient's response to therapy. Indium-111 bone-marrow imaging is useful both in evaluating marrow erythroid activity and in following the response to therapy in patients with these diseases

  8. Early image acquisition after administration of indium-111 platelets in clinically suspected deep venous thrombosis

    International Nuclear Information System (INIS)

    Farlow, D.C.; Ezekowitz, M.D.; Rao, S.R.; Martinez, C.; Denny, D.F.; Morse, S.S.; Decho, J.S.; Wackers, F.; Strauss, E.

    1989-01-01

    Indium-111 platelet scintigraphy accurately detects acute deep venous thrombosis in asymptomatic high-risk patients and may be used as a surveillance test. However, its value in symptomatic patients and its accuracy early after platelet injection are not satisfactorily established. The latter is important for timely institution of therapy. Accordingly, 65 patients (67 limbs) with suspected deep venous thrombosis (symptom duration 8 +/- 10 days, mean +/- standard deviation) were prospectively studied with platelet scintigraphy and contrast venography. Platelets were labeled with 405 +/- 101 mCi indium-111 oxine. The labeling efficiency was 80 +/- 10%. All images were acquired within 120 minutes after intravenous administration of the platelet suspension. Both platelet scintigraphy and venography were interpreted independently by 2 blinded observers (for each technique). Five separate analyses were performed. Each scintigraphic reader was compared to each venographic reader. A fifth analysis--consisting of readings with blinded agreement of both readings of the platelet scans and both readings of the venograms--was performed. Interobserver agreement was 92% for venography and 79% for scintigraphy. Excluding anticoagulated patients, the sensitivity of platelet scintigraphy was between 38 and 46% and the specificity was between 92 and 100%. Thus, early imaging of labeled platelets for the diagnosis of symptomatic deep venous thrombosis carries a high specificity but a much lower sensitivity. It is speculated that the low sensitivity is related to the inactivity of the thrombus. This may suggest that early imaging will only be useful in patients whose symptoms are of recent onset

  9. Imaging the inflammatory response to acute myocardial infarction in man using indium-111-labeled autologous platelets

    International Nuclear Information System (INIS)

    Davies, R.A.; Thakur, M.L.; Berger, H.J.; Wackers, F.J.T.; Gottschalk, A.; Zaret, B.L.

    1981-01-01

    The feasibility of imaging the inflammatory response to acute transmural myocardial infarction in man using indium-111 ( 111 In)-labeled autologous leukocytes was assessed in 36 patients. Indium-111 leukocytes were injected i.v. 18 to 112 hs after the onset of chest pain. Cardiac imaging was performed 24 hs later with a mobile gamma camera. Twenty-one patients had positive images and 15 had negative images. The percent of positive images increased as the interval between infarction and 111 In-leukocyte injection shortened; all patients injected within 24 hs of infarction had positive images. Patients with positive images were injected with 111 In leukocytes earlier after infarction and were younger than those with negative images. Several other parameters that could possibly have affected the imaging results were examined and were not significantly different in patients with positive and negative images. These included peak serum creatine kinase, location of infarction, incidence of pericarditis, use of antiinflammatory drugs or membrane-active antiarrhythmic drugs, peripheral leukocyte count, and cell labeling efficiency. The function of the labeled cells was similar in patients with positive and negative images. Six patients with acute infarction serving as controls and given free 111 In-oxine and six patients with stable coronary artery disease given 111 In-leukocytes all had negative cardiac images

  10. Indium-111-chloride and three-phase bone scintigraphy: A comparison for imaging experimental osteomyelitis

    International Nuclear Information System (INIS)

    Hoskinson, J.J.; Daniel, G.B.; Patton, C.S.

    1991-01-01

    To investigate the utility of indium-111-chloride ( 111 In-Cl) imaging in detecting osteomyelitis complicating surgical or fracture sites, the proximal tibia of 11 dogs were experimentally infected with Staphylococcus aureus after creation of a cortical defect. The contralateral limb served as a sham-operated control. Animals were serially imaged by radiography, three-phase technetium-99m-methylene diphosphonate (99mTc-MDP) scintigraphy, and 111 In-Cl scintigraphy. There was a significant difference between infected (1.93) and noninfected (1.32) limb's tibia/femur count density ratios on 24-hr (p = 0.0001) and 72-hr (p = 0.0001) 111 In-Cl images. A smaller difference was found for 99mTc-MDP bone-phase tibia/femur ratios (p = 0.0199). Using receiver operator characteristic analysis of tibia/femur ratios, a sensitivity of 61%, specificity of 88%, and positive (75%) and negative (79%) predictive values were determined for the 24-hr 111 In-Cl images. Indium-111-chloride was superior to 99mTc-MDP in differentiating infected and noninfected operative sites

  11. Endothelial cell labeling with indium-111-oxine as a marker of cell attachment to bioprosthetic surfaces

    International Nuclear Information System (INIS)

    Sharefkin, J.B.; Lather, C.; Smith, M.; Rich, N.M.

    1983-01-01

    Canine vascular endothelium labeled with indium-111-oxine was used as a marker of cell attachment to vascular prosthetic surfaces with complex textures. Primarily cultured and freshly harvested endothelial cells both took up the label rapidly. An average of 72% of a 32 micro Ci labeling dose was taken up by 1.5 X 10(6) cells in 10 min in serum-free medium. Over 95% of freshly labeled cells were viable by trypan blue tests and only 5% of the label was released after 1 h incubations at 37 degrees C. Labeled and unlabeled cells had similar rates of attachment to plastic dishes. Scanning electron microscopic studies showed that labeled cells retained their ability to spread on tissue culture dishes even at low (1%) serum levels. Labeled endothelial cells seeded onto Dacron or expanded polytetrafluoroethylene vascular prostheses by methods used in current surgical models could be identified by autoradiography of microscopic sections of the prostheses, and the efficiency of cell attachment to the prosthesis could be measured by gamma counting. Indium-111 labeling affords a simple and rapid way to measure initial cell attachment to, and distribution on, vascular prosthetic materials. The method could also allow measurement of early cell loss from a flow surface in vivo by using external gamma imaging

  12. Peripheral vascular investigations using indium 111 labeled platelets. Correlation between anatomical and scintigraphic data. A study of 131 cases

    International Nuclear Information System (INIS)

    Bernard, P.J.; Bazan, M.; Laforte, C. de.

    1985-01-01

    In comparison with other arterial investigations, indium 111 labeled scintigraphy appears to be a very suitable tool for the detection and observations of small foci of thrombosis and particularly for the determination of the evolutive character of the lesion. The conservation of the functional properties of labeled platelets is a determining factor in the results obtained [fr

  13. Appearance of acute gouty arthritis on indium-111-labeled leukocyte scintigraphy

    International Nuclear Information System (INIS)

    Palestro, C.J.; Vega, A.; Kim, C.K.; Swyer, A.J.; Goldsmith, S.J.

    1990-01-01

    Indium-111-labeled leukocyte scintigraphy was performed on a 66-yr-old male with polyarticular acute gouty arthritis. Images revealed intense labeled leukocyte accumulation in a pattern indistinguishable from septic arthritis, in both knees and ankles, and the metatarsophalangeal joint of both great toes, all of which were involved in the acute gouty attack. Joint aspirate as well as blood cultures were reported as no growth; the patient was treated with intravenous colchicine and ACTH for 10 days with dramatic improvement noted. Labeled leukocyte imaging, repeated 12 days after the initial study, revealed near total resolution of joint abnormalities, concordant with the patient's clinical improvement. This case demonstrates that while acute gouty arthritis is a potential pitfall in labeled leukocyte imaging, in the presence of known gout, it may provide a simple, objective, noninvasive method of evaluating patient response to therapy

  14. Scintigraphic detection of carotid atherosclerosis with indium-111-labeled autologous platelets

    International Nuclear Information System (INIS)

    Davis, H.H.; Siegel, B.A.; Sherman, L.A.; Heaton, W.A.; Naidich, T.P.; Joist, J.R.; Welch, M.J.

    1980-01-01

    Using autologous platelets labeled with indium-111-oxine, we studied the localization of platelets on arterial lesions by radionuclide scintigraphy in 34 patients with suspected cerebrovascular disease. The imaging results were compared with the findings of contrast angiography in 23 patients, 16 of whom were receiving antiplatelet and/or anticoagulant drugs during the platelet imaging study. Angiography demonstrated atherosclerotic lesions at 33 sites in the extracranial arteries of 16 of these patients. There was accumulation of 111 In-platelets at 20 of these sites (61%) and at three other sites without definite angiographic abnormalities. Lesions with stenoses 111 In-labeled autologous platelets may be useful for evaluating the pathophysiologic characteristics of atherosclerotic lesions in patients with cerebrovascular disease

  15. Indium-111-oxine labeled platelet kinetics in patients with diabetes mellitus

    International Nuclear Information System (INIS)

    Forstrom, L.A.; Luikens, B.; Johnson, T.

    1984-01-01

    The possible role of abnormal platelet function in the pathogenesis of vascular disease in patients with diabetes mellitus remains controversial. In vitro studies have shown variable alterations in platelet function in such patients. Studies of in vivo platelet kinetics in diabetic patients have been inconclusive, although decreased platelet survival has been observed in some cases. Earlier studies were carried out using chromium-51 or selenium-75 for platelet labeling. The authors have performed Indium-111-oxine labeled platelet kinetic and biodistribution studies in 4 patients with diabetes mellitus (ages 49-61 years), and in 4 control subjects (ages 46-60 years). All subjects were male. All diabetic patients were poorly controlled at the time of study, with blood glucose > 140 mg% and hemoglobin A-1c > 10%. Autologous platelets were labeled with Indium-111-oxine in ACD:plasma by previously reported methods, and reinjected in a dose of approximately 50 μCi (range 42-67μCi). Average recovery of the injected platelets was 67% (range 41-85%). Computer analyzed images at 24 hours showed no significant difference in liver uptake between diabetic and control subjects. Mildly increased splenic uptake in diabetic patients was of borderline significance (p=.07). Platelet survival was slightly decreased in diabetic subjects by 3 of 4 models utilized (linear, exponential, multiple hit and weighted mean), although the difference achieved significance only for the weighted man model (p=.05). These data support observations by earlier methods which suggest that platelet survival may be decreased in patients with diabetes mellitus

  16. Assessment of the risk to patients from the labelling of leucocytes with indium-111

    International Nuclear Information System (INIS)

    Edwards, A.A.; Lloyd, D.C.

    1986-01-01

    Indium-111 oxine is used in diagnostic nuclear medicine to label leucocytes. A typical procedure might be to label white cells in 50 ml of blood with about 500 μCi (∼ 20 MBq) of indium-111 and return them to the body. Both theoretical and experimental information from measurements of chromosome aberrations in lymphocytes show that the labelled cells receive doses of some tens of grays, mostly delivered within one to two weeks. Much of the dose is due to short range Auger electrons. The doses to organs of the body due to circulating labelled cells are much lower. The risk to the patient thus has two components, due to the low dose irradiation of body organs and the localized high dose to the labelled cells. The former is estimated using the concept of effective dose equivalent as recommended by ICRP. An effective dose equivalent of 2 x 10 -2 Sv x mCi -1 for the above procedure was calculated making use of recent data on the distribution of the label within the body. The resulting risk of inducing a fatal cancer is calculated as about 3 x 10 -4 mCi -1 . Attempts to evaluate the risk of leukemia and lymphatic cancer due to direct irradiation of labelled leucocytes are more difficult. If cellular doses are as high as 50 Gy, cell killing can be used to argue that the risk is much lower than the whole-body risk. For lower cellular doses an argument based on the fraction of cells irradiated is used and the risk due to the labelled cells appears to be two orders of magnitude lower than the whole-body risk. 30 references, 1 figure, 3 tables

  17. A comparison of gallium-67 citrate scintigraphy and indium-111 labelled leukocyte imaging for the diagnosis of prosthetic joint infection. Preliminary results

    International Nuclear Information System (INIS)

    McKillop, J.H.; Cuthbert, G.F.; Gray, H.W.; McKay, Iain; Sturrock, R.D.

    1982-01-01

    Preliminary experience in comparing Gallium-67 imaging in patients with a painful prosthetic joint to the findings on Indium-111 labelled leukocyte imaging is reported. In the small series of patients so far studied, no clear advantage has emerged for either Gallium-67 or Indium-111 leukocyte imaging in terms of sensitivity or specificity for joint prosthesis infection. Should a larger group confirm the preliminary findings, Gallium-67 imaging may be preferable to Indium-111 leukocyte imaging in the patient with the painful joint prosthesis, in view of the greater simplicity of the former technique

  18. Comparison of indium-111 platelet scintigraphy and two-dimensional echocardiography in the diagnosis of left ventricular thrombi

    International Nuclear Information System (INIS)

    Ezekowitz, M.D.; Wilson, D.A.; Smith, E.O.; Burow, R.D.; Harrison, L.H. Jr.; Parker, D.E.; Elkins, R.C.; Peyton, M.; Taylor, F.B.

    1982-01-01

    In a study comparing indium-111 platelet scintigraphy and two-dimensional echocardiography as methods of identifying left ventricular thrombi, the results obtained with both techniques were verified at surgery or autopsy in 53 patients-34 with left ventricular aneurysms, and 19 with mitral-valve disease. Left ventricular thrombi were found at surgery or autopsy in 14 of the patients with aneurysms and in none of those with mitral-valve disease. Thirteen of 53 echocardiograms (25%) were technically inadequate and excluded from the analysis. In the group with aneurysms, the sensitivity of scintigraphy in detecting thrombi was 71%, and that of echocardiography was 77%. The specificity of scintigraphy was 100%, and that of echocardiography was 93%. We conclude that indium-111 platelet scintigraphy and two-dimensional echocardiography have useful and complementary roles in the detection of left ventricular thrombi. Both these noninvasive techniques can be used to monitor therapy

  19. Identification of intracardiac thrombi in stroke patients with indium-111 platelet scintigraphy

    International Nuclear Information System (INIS)

    Kessler, C.; Henningsen, H.; Reuther, R.; Kimmig, B.; Roesch, M.

    1987-01-01

    Platelet scintigraphy (PSC) with indium-111 labelled platelets has been confirmed as an adequate method for the detection of intracardiac thrombi in patients with heart disease. We performed PSC of the heart and the neck vessels in 27 stroke patients with suspected cardiac embolism and as control on 10 patients with atherosclerotic lesions of the carotid arteries without evidence of heart disease. The carotid PSC was positive in 6 of 10 patients with carotid disease, and twice in the 27 with suspected cardiac embolism. In these 27 the PSC of the heart indicated pathological conditions 13 times. Pathological platelet accumulations could be visualized in 3 cases in the atrial space, in 9 cases in the region of the left ventricle, and once at the aortic valve. Scintigraphy was negative in all 10 patients with atherosclerosis of the neck vessels. The two-dimensional echocardiography revealed pathological findings in 8 of the 13 patients with positive heart PSC (3 with intraventricular thrombi, 3 with valvular disease, 2 with decreased ventricular contractility) and was normal in the 10 control patients. Open-heart surgery was performed in 2 patients with pathological PSC and revealed an intracardiac thrombus. Three of 4 patients with positive atrial PSC showed mitral or aortic valve disease. These results suggest that PSC can provide a valuable method for detecting cardiac thrombi in stroke patients

  20. Indium-111 tropolone, a new high-affinity platelet label: preparation and evaluation of labeling parameters

    International Nuclear Information System (INIS)

    Dewanjee, M.K.; Rao, S.A.; Didisheim, P.

    1981-01-01

    Platelets were isolated with a new neutral, lipid-soluble metal complex of indium-111 and tropolone. Unlike oxine, which must be dissolved in ethyl alcohol, tropolone is soluble saline. Platelet labeling with In-111 tropolone can be performed in both acid-citrate-dextrose (ACD)-plasma and ACD-saline media within two hours' time. Labeling efficiency has been 80-90% in ACD-saline and 60-70% in the ACD-plasma medium. Optimum concentrations for the labeling of platelets with In-111 tropolone were 5 micrograms/ml in ACD-saline and 10 micrograms/ml in ACD-plasma, using a 15-min incubation at room temperature. A kit formulation for convenient routine preparation of In-111-labeled platelets has been developed. Seven parameters of platelet labeling were studied: concentration of tropolone, citrate, plasma proteins, and calcium ions; also platelet density, temperature, and pH of incubation medium. Their effects on the mechanism of platelet labeling with lipid-soluble tracers are discussed

  1. A quantitative study of Indium-111-oxine platelet kinetics in acute and chronic renal transplant rejection

    International Nuclear Information System (INIS)

    Heyns, A. du P.; Pieters, H.; Badenhorst, P.N.; Wessels, P.; Loetter, M.G.; Minnaar, P.C.; Pauw, F.H.

    1982-01-01

    Thirteen patients were investigated on 22 occasions at times varying from 1 day to 10 years after living family donor or cadaver renal transplantation. Platelet survival in the circulation, and in vivo platelet distribution and sites of deposition and sequestration was quantitatively determined with Indium-111-oxine (In-111-oxine) labelled platelets and a scintillation camera interfaced with a computer assisted imaging system. In all patients platelet survival was shortened and the platelet survival curve exponential. In patients with no evidence of transplant rejection and those with chronic rejection, there was no measurable or visible accumulation of labelled platelets in the kidney. The sequestration pattern of In-111 labelled platelets at the end of platelet life span was within normal limits and located in the reticuloendothelial system. In those patients with acute transplant rejection, platelet survival was shortened. Labelled platelets accumulated in the kidney: this was clearly visualized on scintigraphy and reflected by a significant increase in the radioactivity count density of the kidney. Platelets not deposited in the transplant were sequestrated in the reticuloendothelial system. This study demonstrates the diagnostic value of In-111 labelled platelet kinetics in the investigation of acute renal failure after renal transplantation. This investigation appears of limited clinical value in chronic rejection. (orig.)

  2. Role of delayed indium-111 labeled leukocyte scan in the management of Crohn's disease

    International Nuclear Information System (INIS)

    Slaton, G.D.; Navab, F.; Boyd, C.M.; Diner, W.C.; Texter, E.C. Jr.

    1985-01-01

    Comparison of nine patients with Crohn's disease who had a positive delayed (24 hr) 111 indium leukocyte scan and 10 patients with negative scan showed no significant difference between the two groups for the Crohn's disease activity index, sedimentation rate, survival, complications, number of days in hospital, outpatient visits, or readmissions. Despite the apparent lack of statistical significance in Crohn's disease activity index, the scan was positive in nine of 16 patients with a Crohn's disease activity index more than 150, and none of three patients with Crohn's disease activity index less than 150. In the patients studied, there were no false-positive leukocyte scans. In nine of 10 patients with ileocolonic disease, scanning results correctly predicted the proper management. Six patients with positive scan and enteroclysis responded to medical treatment. Four patients had positive enteroclysis and negative scan; of these, three had radiographic features of chronic ileal stricture which was confirmed at operation. The results suggest that a negative delayed indium-111 leukocyte scan may be useful in diagnosis of chronic fibrotic ileal stricture

  3. Indium-111 labeled purified granulocytes in the diagnosis of synthetic vascular graft infection

    International Nuclear Information System (INIS)

    Forstrom, L.A.; Dewanjee, M.K.; Chowdhury, S.; Brown, M.L.

    1988-01-01

    Indium-111 labeled leukocytes have been shown to be useful in the diagnosis of synthetic vascular graft infection. To minimize the potential effects of labeled red blood cells and platelets on image interpretation, the authors prepared purified autologous granulocytes (PG) from 84 ml of blood using Volex enhanced gravity sedimentation and Ficoll-Hypaque double density centrifugation. The labeling efficiency of PG with In-111 tropolone was 90 +/- 9% (mean +/- SD). Imaging was performed 18-24 hours following injection of approximately 445 microcuries of In-111 PG in 26 patients with suspected infection of vascular grafts that had been implanted 12 days to 12 years prior to the study. In ten patients with proven graft infection, seven had positive In-111 PG scans. Ten of 11 patients without infection had negative scans. In five patients with clinically equivocal findings, scan results were positive in one, negative in one, and equivocal in three. A false-positive scan occurred in a patient with an uninfected inflammatory pseudoaneurysm of an aortic graft. These results confirm an earlier report that In-111 PG imaging is a useful technique in the diagnosis of synthetic vascular graft infection

  4. Indium-111 autologous tagged leukocytes in the diagnosis of intraperitoneal sepsis

    International Nuclear Information System (INIS)

    Ascher, N.L.; Ahrenholz, D.H.; Simmons, R.L.; Weiblen, B.; Gomez, L.; Forstrom, L.A.; Frick, M.P.; Henke, C.; McCullough, J.

    1979-01-01

    The results of a new test using indium oxine in the diagnosis of postoperative infection are reported. Indium-111 was used to label autologous polymorphonuclear leukocytes, which when reinjected migrate to sites of infection and inflammation. Standard scintigraphy localizes the labeled inflammatory cells at these sites. Sixty-six scans were performed in 43 surgical patients. Thirty-seven scans were categorized as true-positive; 19 scans were categorized as true-negative. Therefore, the accuracy rate was 85%. Two scans (3%) in one patient represented false-positive results. Two scans (3%) were positive for inflammation but there was no infection present; this group was denoted as equivocal. Six scans (9%) were false-negative; false-negative scans are more likely in old lesions with poor blood supply and in areas that overlap regions of normal uptake. The noninvasive nature of the test, high accuracy rate, and ease of administration make it a potentially useful tool in the diagnosis of postoperative infection

  5. Vessel wall and indium-111-labelled platelet response to carotid endarterectomy

    International Nuclear Information System (INIS)

    Lusby, R.J.; Ferrell, L.D.; Englestad, B.L.; Price, D.C.; Lipton, M.J.; Stoney, R.J.

    1983-01-01

    Postendarterectomy platelet deposition and thrombus formation may play an important role not only in vessel wall healing but also in the small incidence of postoperative cerebral ischemia and postoperative stenosis. A study has been performed using a canine model to investigate the healing response to carotid endarterectomy and the validity of an in vivo indium-111 (In-111) radiotracer technique in the assessment of postendarterectomy deposition of autologous labelled platelets. Sixteen endarterectomized carotid arteries showed uptake of autologous In-111 platelets immediately after infusion, reaching a maximum by 1 hour with little increase at 24 or 48 hours. No uptake was seen in ten control vessels following platelet infusion (P less than 0.05). At autopsy, seven vessels were demonstrated to have In-111 platelet deposition immediately prior to sacrifice of the animals. Postmortem scanning confirmed the localization to the vessel lumens, and microscopy revealed thrombus formation with or without partial endothelialization. Complete reendothelialization had occurred in the vessels that failed to show platelet deposition. Delayed healing was associated with continuing platelet deposition, excessive thrombus formation, and luminal stenosis. Arteriotomy closure with a vein patch altered the healing characteristics of the vessel with segmental thrombus formation over the vein patch. A preliminary study of the postendarterectomy in vivo In-111 platelet response in humans demonstrated platelet deposition that was not influenced by the administration of antiplatelet drugs at currently prescribed levels

  6. Role of indium-111 labelled platelet scintigraphy in the management of thrombocytopenic patients with malignant neoplasms

    Energy Technology Data Exchange (ETDEWEB)

    Oriuchi, N.; Korkmaz, M.; Kim, E.E.; Delpassand, E.S.; Wong, F.; Podoloff, D.A. [Texas Univ., Houston, TX (United States). Dept. of Nuclear Medicine; Wallace, S. [Texas Univ., Houston, TX (United States). Dept. of Diagnostic Radiology

    1998-03-01

    This study was done to investigate the role of indium-111 labelled platelet scintigraphy in the treatment of thrombocytopenia in patients with malignant neoplasms. The study involved 20 consecutive patients with thrombocytopenia associated with malignant neoplasms or hematological disorders and without evidence of underproduction of megakaryocytes due to chemotherapy or bone marrow infiltration by the malignancy. Splenic sequestration of platelets was evaluated by measuring spenic uptake of {sup 111}In-labelled platelets, and findings were correlated with the outcome of splenectomy and medication. Of the 20 patients, 13 had splenic sequestration of platelets. Seven of the 13 patients underwent splenectomy; six of these seven patients experienced a complete response. The other six patients received medication only and showed no response. Of the seven patients without splenic sequestration of platelets, five received medication, and four of them responded to it. {sup 111}In-labelled platelet scintigraphy has a role in selecting appropriate therapy and predicting its efficacy in patients with thrombocytopenia associated with malignant neoplasms. (orig.)

  7. Role of indium-111 labelled platelet scintigraphy in the management of thrombocytopenic patients with malignant neoplasms

    International Nuclear Information System (INIS)

    Oriuchi, N.; Korkmaz, M.; Kim, E.E.; Delpassand, E.S.; Wong, F.; Podoloff, D.A.; Wallace, S.

    1998-01-01

    This study was done to investigate the role of indium-111 labelled platelet scintigraphy in the treatment of thrombocytopenia in patients with malignant neoplasms. The study involved 20 consecutive patients with thrombocytopenia associated with malignant neoplasms or hematological disorders and without evidence of underproduction of megakaryocytes due to chemotherapy or bone marrow infiltration by the malignancy. Splenic sequestration of platelets was evaluated by measuring spenic uptake of 111 In-labelled platelets, and findings were correlated with the outcome of splenectomy and medication. Of the 20 patients, 13 had splenic sequestration of platelets. Seven of the 13 patients underwent splenectomy; six of these seven patients experienced a complete response. The other six patients received medication only and showed no response. Of the seven patients without splenic sequestration of platelets, five received medication, and four of them responded to it. 111 In-labelled platelet scintigraphy has a role in selecting appropriate therapy and predicting its efficacy in patients with thrombocytopenia associated with malignant neoplasms. (orig.)

  8. Imaging experimental infective endocarditis with indium-111-labeled blood cellular components

    International Nuclear Information System (INIS)

    Riba, A.L.; Thakur, M.L.; Gottschalk, A.; Andriole, V.T.; Zaret, B.L.

    1979-01-01

    The capability of radionuclide imaging to detect experimental aortic valve infective endocarditis was assessed with indium-111 ( 111 In)-labeled blood cells. Sequential cardiac imaging and tissue distribution studies were obtained in 17 rabbits with infective endocarditis after administration of 111 In-platelets and in five after 111 In-polymorphonuclear leukocytes. Forty-eight to 72 hours after platelet administration, in vivo imaging demonstrated abnormal 111 In uptake in all animals in the region of the aortic valve in an anatomically distinct pattern. Images of the excised heart showed discrete cardiac uptake conforming to the in vivo image and gross pathological examination. 111 In-platelet uptake in vegetations from the 17 animals averaged 240 +- 41 times greater than that in normal myocardium and 99 +- 15 times greater uptake in blood. In contrast, 111 In-leukocyte cardiac imaging showed no abnormal aortic valve uptake 24 hours after tracer administration and the lesion myocardium activity ratio was only 5 +- 2 (3 +- 1 for lesion/blood activity). Four normal rabbits demonstrated neither positive 111 In-platelet scintigraphs nor abnormal cardiac tissue uptake. Likewise, noncellular 111 In was not concentrated to any significant extent in three animals with infective endocarditis. This study demonstrates that 111 In-platelet, but not leukocyte cardiac imaging, is a sensitive technique for detecting experimental infective endocarditis. The imaging data conform to the cellular pathology of the infective endocarditis vegetation

  9. Indium 111 scintigraphy in the exploration of the erythropoietic marrow (relative to 42 observations)

    International Nuclear Information System (INIS)

    Guerin, G.C.R.

    1976-01-01

    The bone marrow is difficult to explore as a whole because of its wide non-uniform distribution, variable with the hematopoietic and supporting tissue sites. 111 indium-transferrine bone marrow scintigraphy is a new technique which partly overcomes these difficulties and gives an idea of the overall distribution and richness of the erythropoietic marrow, thus showing up the erythropoiesis sites at a given moment. The properties of indium as medullary tracer are bound up with the characteristics of its metabolism which, to some extent at least resembles that of iron. The two main features are: - its fixation on transferrine (or siderophiline); - its binding to reticulocytes. Moreover indium 111 fulfils the physico-chemical criteria necessary for scintigraphic practice (long half-life, emission detectable by conventional scintigraphs, moderate irradiation of the patient). The properties of this radioelement and the technical conditions of use are examined in turn, then scintigraphic data are compared with the results of traditional bone marrow investigations: medullary biopsy and blood cell counts with reticulocyte fraction. This comparison concerns 42 scintigraphs carried out on patients suffering from various hematological diseases, with prospects of serious development in common [fr

  10. Noninvasive detection of rejection of transplanted hearts with indium-111-labeled lymphocytes

    International Nuclear Information System (INIS)

    Eisen, H.J.; Eisenberg, S.B.; Saffitz, J.E.; Bolman, R.M. III; Sobel, B.E.; Bergmann, S.R.

    1987-01-01

    To determine whether cardiac transplant rejection can be detected noninvasively with indium-111 ( 111 In)-labeled lymphocytes, we studied 11 dogs with thoracic heterotopic cardiac transplants without immunosuppression and five dogs with transplants treated with cyclosporine (10 mg/kg/day) and prednisone (1 mg/kg/day). All were evaluated sequentially with gamma scintigraphy after administration of 150 to 350 muCi of autologous 111 In-lymphocytes. Technetium-99m-labeled red blood cells (1 to 3 mCi) were used for correction of radioactivity in the blood pool attributable to circulating labeled lymphocytes. Lymphocyte infiltration was quantified as the ratio of indium in the myocardium of the transplant or native heart compared with that in blood (indium excess, IE). Results were correlated with mechanical and electrical activity of allografts and with histologic findings in sequential biopsy specimens. In untreated dogs (n = 11), IE was 15.5 +/- 7.0 (SD) in transplanted hearts undergoing rejection and 0.4 +/- 1.1 in native hearts on the day before animals were killed. In dogs treated with cyclosporine and prednisone (n = 5), IE was minimal in allografts during the course of immunosuppression (0.8 +/- 0.4) and increased to 22.9 +/- 11.1 after immunosuppression was stopped. Scintigraphic criteria of rejection (IE greater than 2 SD above that in native hearts) correlated with results of biopsies indicative of rejection and appeared before electrophysiologic or mechanical manifestations of dysfunction. Thus infiltration of labeled lymphocytes in allografts, indicative of rejection, is detectable noninvasively by gamma scintigraphy and provides a sensitive approach potentially applicable to clinical monitoring for early detection of rejection and guidance for titration of immunosuppressive measures

  11. Left ventricular thrombi: in vivo detection by indium-111 platelet imaging and two dimensional echocardiography

    International Nuclear Information System (INIS)

    Stratton, J.R.; Ritchie, J.L.; Hamilton, G.W.; Hammermeister, K.E.; Harker, L.A.

    1981-01-01

    Indium-111 platelet imaging, which can identify sites of active intravascular platelet deposition, and two dimensional echocardiography, which can identify intracardiac masses, can both be used to detect left ventricular thrombi noninvasively. We compared these techniques in 44 men at risk for thrombi from remote transmural myocardial infarction (31 patients) or cardiomyopathy (13 patients). All 44 patients underwent platelet imaging; 35 underwent echocardiography. On platelet imaging nine patients had thrombi and onehad a possible thrombus. Of these 10 studies, none were positive at 2 hours, 5 were positive at 24 hours and all were positive 48 or 72 hours after platelet labeling. Nine of these patients underwent echocardiography, and all had an intraventricular mass. The findings on platelet scanning were negative in six patients who had positive (four patients) or equivocally positive (two patients) findings on echocardiography. All patients with thrombi detected by either noninvasive method had transmural anterior myocardial infarction with ventricular aneurysm. Of the seven patients who underwent cardiac surgery or autopsy, three had thrombi. Platelet imaging failed to identify one thrombus in a patient in whom imaging was performed only at 24 hours after labeling. There were no false positive platelet images in this group. Five of these seven patients (two with throbi, three without) underwent echocardiography; in all cases the echocardiographic findings agreed with the pathologic findings. Both platelet imaging and echocardiography detect ventricular thrombi. Platelet imaging may detect only the most hematologically active thrombi. Both techniques may help define patients at risk of embolization and may be useful for in vivo assessment of antithrombotic drugs

  12. Reduction of indium-111 platelet deposition on Dacron vascular grafts in humans by aspirin plus dipyridamole

    International Nuclear Information System (INIS)

    Stratton, J.R.; Ritchie, J.L.

    1986-01-01

    Aspirin plus dipyridamole reduces platelet accumulation on short-term Dacron vascular grafts in man. To determine whether drug inhibition of platelet deposition is sustained on older grafts, we studied 18 men aged 41 to 87 years who had Dacron aortic bifurcation grafts in place a mean of 43.4 months (range 9.8 to 121.0) before and during short-term therapy with aspirin (325 mg tid) plus dipyridamole (75 mg tid). During both the baseline and drug studies, indium-111 ( 111 In) platelet deposition was quantitated by two techniques, standard planar imaging performed at 24, 48, and 72 hr after injection of platelets and single photon emission computed tomographic imaging performed at 24 and 72 hr after injection. All analyses were performed in a blinded fashion. On both the planar and tomographic images, platelet accumulation on the graft was quantitated by a graft/blood ratio that compared activity in the graft to simultaneously collected whole blood 111 In platelet activity. Aspirin plus dipyridamole reduced the tomographic graft/blood ratio at 24 hr (20.6 +/- 3.5 vs 17.3 +/- 2.5) (+/-SEM) and at 72 hr (29.0 +/- 4.8 vs 25.0 +/- 4.1) after injection of platelets (p = .02). Dacron vascular grafts. Similarly, the planar graft/blood ratio was reduced at 24 hr (2.7 +/- 0.5 vs 2.4 +/- 0.5), 48 hr (3.7 +/- 0.9 vs 3.1 +/- 0.7), and 72 hr (4.0 +/- 0.9 vs 3.6 +/- 0.8) (p = .04). We conclude that aspirin (325 mg tid) plus dipyridamole (75 mg tid) reduces platelet accumulation on long-term Dacron vascular grafts

  13. Diagnosis of cardiac allograft rejection with indium-111 labeled platelets in cyclosporin treated rats

    International Nuclear Information System (INIS)

    Fawwaz, R.A.; Iga, C.; Hardy, M.A.; Alderson, P.O.

    1984-01-01

    Rejection of heart transplants remains difficult to diagnose. Indium-111 (In-111) labeled lymphocytes accumulate in rat cardiac allografts when recipients are treated with Cyclosporin (Cy), even in the absence of clinical rejection. This presumably occurs because of the non-specific 'interstitial infiltration' caused by Cy. This study examines the usefulness of In-111 labeled platelets in differentiating experimental cardiac allograft rejection from Cy-induced tissue changes. The authors initially examined the migration patterns of syngeneic In-111 labeled platelets in groups of Lewis recipients of ACI cardiac allografts treated with IM Cy (10mg/kg) for 6-14 days. In addition, 10 control animals were not immunosuppressed, and 10 were treated with Cy but received Lewis cardiac isografts. Syngeneic In-111 platelets were injected IV into each animal 24 hours prior to sacrifice. Three to five rats from each group were killed at 3 ,7, 14, 21 and 28 days after transplantation and the % ID/gm in the transplanted hearts and native hearts were determined and correlated with histopathology. Untreated Lewis recipients rejected ACI hearts in 6.5 +- 0.4 days while Cy prolonged allograft survival in a variable fashion. In-111 platelet accumulation correlated well with the degree of rejection determined independently by histopathology. No significant In-111 platelet accumulation was detected in non-rejecting cardiac transplants or in native hearts in Cy treated or control animals. The results suggest that In-111 labeled platelets will be an effective agent for diagnosis of cardiac rejection, even in the presence of Cy treatment

  14. Biokinetics of indium-111 labeled platelets after cryotherapy of hepatic metastases

    International Nuclear Information System (INIS)

    Alexander, C.; Kirsch, C.-M.; Pistorius, G.; Feifel, G.

    2002-01-01

    Full text: The present investigation was performed to evaluate mean platelet live-span and the proportion of platelet disposal in different organs in patients after hepatic cryotherapy. Seven patients with advanced colorectal cancer and liver metastases were included. Directly before the surgical procedure a blood specimen was drawn and an in vitro labeling of patients platelets with 18 MBq Indium-111 oxime was performed. Reinjection was done intraoperatively just before cryotherapy. Blood specimen were drawn at 1, 2, 3, 24 und 48 h p.i.. Whole-body scintigraphy was acquired on day two alter operation. The evaluation comprised the calculation of mean platelet live-span and of organ activities as percentage of whole-body activity. The local disposal of platelets at the site of cryotherapy ranged from 0 to 35.2 percent, the mean value was 16,2 ± 12,2 percent (mean ± SD). The mean half-time of time-activity curve gave 0.6 to 2.4 days (mean ± SD: 1.6 ± 0.6 d; normal value: 3.5-6 d), the mean platelet life-span was between 2.1 and 5.2 days corresponding to a mean value of 3.4 ± 1.0 days (normal value: 7-11 d). The evaluation of SPECT slices of large liver metastases demonstrated that platelet disposal takes place at the border zone of the metastases just around the necrotic center. We conclude that the enhanced local platelet trapping is a major cause for cryothermia-induced systemic thrombocytopenia. (author)

  15. Limitations in the use of indium-111-oxine-labeled leucocytes for the diagnosis of occult infection in children

    Energy Technology Data Exchange (ETDEWEB)

    Haentjens, M.; Piepsz, A.; Perlmutter-Cremer, N.; Schell-Frederick, E.; Fruehling, J.

    1987-02-01

    Fifteen children underwent scintigraphy with indium 111 (/sup 111/In)-labeled white blood cells (WBC) for the detection of a local suppuration. The procedure generally contributed to a correct diagnosis. False negative results were observed in 5 children, but in two of them positive foci were also present. The missed lesions were 2 liver abscesses, 1 lung abscess, foci of osteomyelitis and 1 pericarditis. Two cases of chronic granulomatous disease are presented in which increased leucocyte accumulation was not observed in proven instances of infection.

  16. Use of Take-set system for radiopharmaceutical labelling: example of indium-111 labeled pentetreotide (Octreoscan) preparation

    International Nuclear Information System (INIS)

    Ben Reguiga, M.; Sinegre, M.; Besse, H.; Stievenart, J.L.; Le Guludec, D.

    2009-01-01

    The quality of indium 111 radiolabelled pentetreotide preparation (Octreoscan, Covidien) depends on several factors among which the use of a special transfer needle (Sterican) especially conceived to avoid the metal impurities introduction into the reactional medium during labelling. This device, usually provided by the supplier, can exceptionally present defects (twisted needle, folded bevel...) preventing its use for the preparation. In order to manage this risk, we propose in the present technical note an alternative labelling method, based on an adaptation of the original one and using another transfer device, the Take-setSWAN system, which permits to obtain high quality Octreoscan preparations that meet the product approval specifications. (authors)

  17. Edwardsiella tarda Endocarditis Confirmed by Indium-111 White Blood Cell Scan: An Unusual Pathogen and Diagnostic Modality

    Directory of Open Access Journals (Sweden)

    Kayleigh M. Litton

    2016-01-01

    Full Text Available Edwardsiella tarda is a freshwater marine member of the family Enterobacteriaceae which often colonizes fish, lizards, snakes, and turtles but is an infrequent human pathogen. Indium-111- (111In- labeled white blood cell (WBC scintigraphy is an imaging modality which has a wide range of reported sensitivity and specificity (from 60 to 100% and from 68 to 92%, resp. for diagnosing acute and chronic infection. We describe a case of suspected E. tarda prosthetic aortic valve and mitral valve endocarditis with probable vegetations and new mitral regurgitation on transthoracic and transesophageal echocardiograms which was supported with the use of 111In-labeled WBC scintigraphy.

  18. The value of indium 111 leukocyte scanning in the evaluation of painful or infected total knee arthroplasties

    International Nuclear Information System (INIS)

    Rand, J.A.; Brown, M.L.

    1990-01-01

    Evaluation of painful total knee arthroplasties (TKAs) for infection can be difficult. Indium 111 ( 111 In) leukocyte bone scanning provides a minimally invasive technique for evaluation of possible infection. Thirty-eight patients with a painful TKA who had surgical exploration after 111 In leukocyte scanning were reviewed. The scan had an accuracy of 84%, a sensitivity of 83%, and a specificity of 85%. The 111 In leukocyte scans must be interpreted in conjunction with the clinical evaluation of the patient because they are less accurate for study of TKAs than of total hip arthroplasties

  19. Localization of indium-111 in human malignant tumor xenografts and control by chelators

    International Nuclear Information System (INIS)

    Watanabe, Naoyuki; Oriuchi, Noboru; Endo, Keigo; Inoue, Tomio; Tanada, Shuji; Murata, Hajime; Kim, E. Edmund; Sasaki, Yasuhito

    1999-01-01

    The kinetics of soluble indium-111 ( 111 In) in human malignant tumor xenografts and cells was investigated in combination with chelators. Firstly, without chelator, the kinetics of 111 In-chloride was investigated in vitro and in vivo using four human malignant neuroblastoma SK-N-MC, pulmonary papillary adenocarcinoma NCI-H441, pulmonary squamous cell carcinoma PC 9, and colon adenocarcinoma LS 180 cells and xenografts. 111 In was incorporated into tumor cells in vitro to a maximum level during a 60-min incubation. A maximum level of radioactivity was demonstrated in vivo in four human malignant tumors xenografted into nude mice at 24 h postinjection of 111 In-chloride. Secondly, the effect of edetate calcium disodium (CaNa 2 EDTA) on radioactivity in 111 In-labeled tumors xenografts and cells was studied in vitro and in vivo. CaNa 2 EDTA significantly reduced 111 In-activity from the labeled tumor xenografts, whereas it had no affect on the radioactivity in the labeled cells. Thirdly, the effect of CaNa 2 EDTA on radioactivity in human malignant tumors xenografted into nude mice injected with 111 In-chloride was investigated. In one group of mice CaNa 2 EDTA administered intraperitoneally at 1, 22, 34, 46, 58, and 70 h after injection of 111 In-chloride (postadministration), the localization of 111 In at the tumors was significantly decreased at 72 h compared with the control in all four tumor types. In the other group of mice, CaNa 2 EDTA administered intraperitoneally at 12 and 1 h before injection of 111 In-chloride and 1, 22, 34, 46, 58, and 70 h postinjection (pre- and postadministration), the radioactivity of tumors was also significantly decreased at 72 h, and the reduction was greater than that with use of postadministration. In a comparative study, CaNa 3 DTPA had a more powerful effect than CaNa 2 EDTA. In conclusion, 111 In-activity in tumors consists of intracellular and extracellular components, and the extracellular 111 In may be cleared by

  20. Uptake of indium-111 labelled platelets by normal, nephrotic and transplanted kidneys

    International Nuclear Information System (INIS)

    Desir, G.; Lange, R.; Smith, E.; Bia, M.; Flye, M.; Kashgarian, M.; Canganelli, A.; Ezekowitz

    1984-01-01

    To determine the role of platelets in the genesis of renal transplant (T) rejection, the authors studied 3 groups of adult patients. Group I, n=8, had normal renal function (Cr=1 +- 0.1 mg%, Mean +- SD). Group II, n=9, had nephrotic syndrome (Cr=2.4 +- 1). Group III, n=7, consisted of 5 cadaveric (C) and 2 living related donor (LRD) T. In Group II, 1 patient had received a T 4 years prior to study. Group I and II received 448 +- 101 μCi and Group III 236 +- 51 μCi of Indium-111. In Groups I and II the first image was obtained 18 +- 6 hrs after injection. In Group II the first was obtained 6 +- 2 hr after injection and 1-3 times/day thereafter for a maximum of 7 days. Renal biopsies were obtained in all patients in Group III during imaging (n=5) or within 2 - 5 days of the last image. One patient was studied twice. In Group III, 5 patients received prednisone and azothiaprine and 2 prednisone and cyclosporine. Platelet uptake index (PUI) was calculated as the ratio of uptake over the T against a reference area. Rejection was diagnosed by biopsy. In groups I and II platelet uptake was seen only in the T patient. In Group III the PUI was 1.54 +- .13 in the rejecting T (n=5), 1.42 +- .2 in the non-rejecting T (n=3), 1.62 in a LRD non-rejecting T and 1.31 (n=2) in C non-rejecting T. In the four patients studied within 5 days of T the PUI was elevated at 1.47 +- .1. The authors conclude that: 1) platelets do not accumulate in normal or nephrotic native kidneys, 2) significant uptake occurs in the first week after C and LRD whether or not rejection is present, and 3) uptake in non-rejecting kidneys cannot be ascribed to perfusion induced endothelial injury since it was present in LRD transplants

  1. Evaluation of aspirin therapy on intracardiac thrombi using indium-111-oxine platelet scintigraphy, two-dimentional echocardiography and left ventriculography

    International Nuclear Information System (INIS)

    Shibuya, Masanori; Irino, Tadayoshi; Yoshioka, Toshiharu; Sugimoto, Tsuyoshi; Tsuji, Kazuo; Naka, Masashi; Arai, Hidekazu.

    1984-01-01

    Left ventriculography (LVG), two-dimensional echocardiography (2-DE) and indium-111-oxine platelet scintigraphy were performed in five patients with intracardiac thrombi. Thrombi were visible in 7 sites (5 in the ventricle and 2 in the atrium) by platelet scintigraphy, in 4 sites (3 in the ventricle and 1 in the atrium) by 2-DE, and in 4 sites (4 in the ventricle) by LVG. When aspirin was administered to the patients, platelet scintigraphy had become negative for thrombi in 5 sites and false-negative for them in 2 sites. However, thrombi were detected in 6 sites after the withdrawal of aspirin. On the other hand, thrombi were detected in 4 sites by 2-DE, irrespective of the administration of aspirin. Indium-111-oxine platelet scintigraphy has proved to not only have higher sensitivity for detecting thrombi but also to be capable of observing the coagulation status of platelets on the thrombi. It is therefore considered very helpful in assessing anticoagulation therapy. (Namekawa, K)

  2. Utility of the indium 111-labeled human immunoglobulin G scan for the detection of focal vascular graft infection

    International Nuclear Information System (INIS)

    LaMuraglia, G.M.; Fischman, A.J.; Strauss, H.W.; Keech, F.; Wilkinson, R.; Callahan, R.J.; Khaw, B.A.; Rubin, R.H.

    1989-01-01

    The ability to diagnose and localize vascular graft infections has been a major challenge. Recent studies in animal models and humans with focal bacterial infection have shown that radiolabeled, polyclonal, human immunoglobulin G accumulates at the site of inflammation and can serve as the basis for an imaging technique. This study investigated this new technique for the diagnosis and localization of vascular graft infections. Twenty-five patients with suspected vascular infections involving grafts (22), atherosclerotic aneurysms (2), and subclavian vein thrombophlebitis (1) were studied. Gamma camera images of the suspected area were obtained between 5 and 48 hours after intravenous administration of 1.5 to 2.0 mCi (56 to 74 mBq) of indium 111-labeled, human, polyclonal immunoglobulin G. Scan results were interpreted without clinical information about the patient and were subsequently correlated with surgical findings, other imaging modalities, and/or clinical follow-up. In 10 of 10 patients found to have positive scan results, localized infections were confirmed at the involved sites. In 14 of 15 patients whose scan results were interpreted as negative, no vascular infections were identified at follow-up. The patient with false-negative results and recurrent bacteremia from an aortoduodenal fistula was found to have a negative scan outcome at a time when his disease was quiescent. These data suggest that nonspecific, human, indium 111-labeled immunoglobulin G scanning can be a useful noninvasive means of localizing vascular infections

  3. Assessment of warfarin therapy under full dose using indium-111 platelet scintigraphy in patients with intracardiac thrombi

    Energy Technology Data Exchange (ETDEWEB)

    Yamada, Makoto; Onishi, Kenji; Fukunami, Masatake and others

    1988-12-01

    Twenty patients in whom intracardiac thrombi were detected by indium-111 platelet scintigraphy (the first platelet scintigraphy) were prospectively studied to examine the effect of warfarin therapy under full dose on the intracardiac thrombogenecity. Eleven patients (group I) who received 2-6 mg/day of warfarin and 9 patients (group II) who did not received warfarin had the second platelet scintigraphies 14-71 days after the first platelet scintigraphies. In group I, 10 platelet scintigraphies became negative and one remained positive for intracardiac thrombi after administration of warfarin, while in group II 8 platelet scintigraphies remained positive and only one changed to negative. The incidence of negative image at the second platelet scintigraphy was significantly lower in group II than that in group I. In group I, the degree of accumulation of platelets onto the surface of the thrombus (%IE), showed significant reduction (0.69+-0.48 to 0.11+-0.21) after warfarin therapy, while in group II %IE at the second scintigraphy (1.07+-1.03) were not significantly different from those at the first scintigraphy (1.13+-0.79). These results indicated that warfarin therapy under full dose inhibited the deposition of platelets on the intracardiac thrombi and thrombogenecity in the patients with intracardiac thrombi which were detected by indium-111 platelet scintigraphy.

  4. Assessment of warfarin therapy under full dose using indium-111 platelet scintigraphy in patients with intracardiac thrombi

    International Nuclear Information System (INIS)

    Yamada, Makoto; Onishi, Kenji; Fukunami, Masatake

    1988-01-01

    Twenty patients in whom intracardiac thrombi were detected by indium-111 platelet scintigraphy (the first platelet scintigraphy) were prospectively studied to examine the effect of warfarin therapy under full dose on the intracardiac thrombogenecity. Eleven patients (group I) who received 2-6 mg/day of warfarin and 9 patients (group II) who did not received warfarin had the second platelet scintigraphies 14-71 days after the first platelet scintigraphies. In group I, 10 platelet scintigraphies became negative and one remained positive for intracardiac thrombi after administration of warfarin, while in group II 8 platelet scintigraphies remained positive and only one changed to negative. The incidence of negative image at the second platelet scintigraphy was significantly lower in group II than that in group I. In group I, the degree of accumulation of platelets onto the surface of the thrombus (%IE), showed significant reduction (0.69±0.48 to 0.11±0.21) after warfarin therapy, while in group II %IE at the second scintigraphy (1.07±1.03) were not significantly different from those at the first scintigraphy (1.13±0.79). These results indicated that warfarin therapy under full dose inhibited the deposition of platelets on the intracardiac thrombi and thrombogenecity in the patients with intracardiac thrombi which were detected by indium-111 platelet scintigraphy. (author)

  5. Study of biodistribution of lipidic nanospheres charged with cis-diaminedichloroplatinum (II) and labelled with radioactive nuclei of Indium-111

    International Nuclear Information System (INIS)

    Lopez R, V.; Juarez O, C.; Medina L, A.; Perez C, E.; Garcia L, P.

    2007-01-01

    The general objective of the study was to evaluate the lipidic nanospheres biodistribution charged with cis-diaminedichloroplatinum (II) (cis-DDP) and labelled with radioactive nuclei of Indium-111 (Lip-Cis-in-111) in Wistar rats and in a tumoral model of CaCu. The conclusions were: 1. The system Lip-Cis-in-111 it presents a very fast elimination probably, to a fast recognition response of the reticuloendothelial system (RES). 2. It is planned to make modifications to the formulation to increase the quantity of the hydrophilic polymer (PEG), so that its time of residence in the blood is bigger and allow a bigger accumulation in the tumor. (Author)

  6. Indium-111-labeled leukocyte scan in detection of synthetic vascular graft infection: The effect of antibiotic treatment

    International Nuclear Information System (INIS)

    Chung, C.J.; Hicklin, O.A.; Payan, J.M.; Gordon, L.

    1991-01-01

    To determine the sensitivity and specificity of the indium-111-( 111 In) labeled leukocyte scan for prosthetic vascular graft infection in patients treated with antibiotic therapy, a retrospective study was performed. Of 41 consecutive 111 In-labeled leukocyte scans performed to evaluate possible vascular graft infection, 23 scans were performed in patients treated with antibiotics. The average duration of antibiotic therapy was 21 days. Twelve positive and 11 negative scans for graft infection were found. By surgical and autopsy correlation of all positive cases, and clinical correlation (of all negative cases), there were 10 true-positive, 11 true-negative, 2 false-positive, and no false-negative scans for graft infections, for an overall sensitivity of 100% and specificity of 85%

  7. Effect of aspirin and ticlopidine on platelet deposition in carotid atherosclerosis: assessment by indium-111 platelet scintigraphy

    International Nuclear Information System (INIS)

    Isaka, Y.; Kimura, K.; Etani, H.; Uehara, A.; Uyama, O.; Yoneda, S.; Kamada, T.; Kusunoki, M.

    1986-01-01

    The antiplatelet effects of aspirin and ticlopidine were studied by a dual-tracer method, using indium-111 labeled platelets and technetium-99m human serum albumin, in a group of 12 patients with suspected ischemic cerebrovascular disease. The magnitude of platelet accumulation at the carotid bifurcation was expressed as the ratio of radioactivity of indium-111 platelets deposited on the vascular wall to those circulating in the blood-pool (PAI, platelet accumulation index), 48 hr after injection of labeled platelets. PAI values were measured before (baseline studies) and after the antithrombotic therapies (aspirin studies: 325 mg bid for 22.3 +/- 1.3 days, ticlopidine studies: 100 mg tid for 21.8 +/- 2.1 days). At the baseline, the mean PAI value at 24 carotid bifurcations in the patient group was 15.7 +/- 15.3% (mean +/- S.D.) compared to -4.3 +/- 9.1 at 24 carotid bifurcations in 12 normal subjects (p less than 0.01). We defined the upper limit for a normal PAI (%) value to be +13.9, namely the mean PAI plus 2 SD for the carotid bifurcation in normal subjects and used this value for semiquantitative analysis. At the baseline, significant elevation of PAI (more than 13.9%; positive scintigram) was observed at 12 of 24 vessels, while 12 other regions were negative (less than 13.9%). In the lesions with positive scintigraphic results at the baseline, the mean PAI (%) value from the baseline, aspirin and ticlopidine studies was 29.5 +/- 7.0, 11.2 +/- 8.5 (p less than 0.01 versus baseline) and 21.4 +/- 21.3 (not significant from baseline), respectively

  8. Indium-111 platelet scintigraphy and two-dimensional echocardiography for detection of left ventricular thrombus: influence of clot size and age

    International Nuclear Information System (INIS)

    Seabold, J.E.; Schroeder, E.C.; Conrad, G.R.

    1987-01-01

    Two-dimensional echocardiography and indium-111 platelet scintigraphy were performed on 50 dogs to determine the influence of clot age and size on the detection of experimentally induced left ventricular mural thrombus. Thrombus was induced by apical infarction and injection of a sclerosing agent and thrombin. The animals were classified into four groups according to the time of indium-111 platelet injection after thrombus induction: Group I (17 dogs, 1/2 hour after induction; 3 dogs, before induction), Group II (12 dogs, 24 hours after induction) and Group III (12 dogs, 1 week after induction). In Group IV (six control dogs) apical infarction was produced, but thrombin was not injected; indium-111 platelets were injected 1/2 to 1 hour after infarction. The dogs were studied by indium-111 platelet scintigraphy and by two-dimensional echocardiography 1/2 to 5 hours (Group I) and 1 to 5 and up to 72 hours (Groups II to IV) after platelet administration and before death was induced. Two-dimensional echocardiography showed the best overall sensitivity for detection of acute thrombus (97%; 29 of 30). The sensitivity of indium-111 platelet scintigraphy was 86% (18 of 21) for clots greater than or equal to 0.08 ml in size, and 67% (20 of 30) for detection of all clots. Thrombus did not form in 14 dogs of Groups I to III and in 6 of 6 control dogs. The specificity of scintigraphy was 100% (20 of 20) compared with 80% (16 of 20) for echocardiography. Echocardiography was more sensitive than scintigraphy for detecting very small clots in this experimental model

  9. Modified procedure for rapid labelling of low concentrations of bioactive proteins with indium-111

    Energy Technology Data Exchange (ETDEWEB)

    Zoghbi, S S; Neumann, R D; Gottschalk, A

    1985-01-01

    The authors describe the conjugation of DTPA to 100-500 g of protein in concentrations of 0.6-1.0 mg mL utilizing the mixed anhydride method. Free DTPA is removed by minicolumn gel filtration and centrifugation with minimal protein dilution. Radiolabelling process can be monitored by instant thin layer chromatography. Any radiochemical impurity detected can be eliminated either by additional minicolumn filtration of further chelation with more conjugated protein. In citrate buffer at pH 6 with minicolumn gel chromatography the authors prepared In-DTPA-D3 (3.0 Ci g) monoclonal antibody and used it to image hepatocarcinoma in guinea pigs. 13 references, 5 figures, 2 tables.

  10. Dual isotope study of iodine-125 and indium-111-labeled antibody in athymic mice

    Energy Technology Data Exchange (ETDEWEB)

    Carney, P.L.; Rogers, P.E.; Johnson, D.K. (Abbott Laboratories, Abbott Park, IL (USA))

    1989-03-01

    Monoclonal antibody B72.3 was coupled to a benzylisothiocyanate derivative of diethylenetriaminepentaacetic acid (DTPA). The maximum substitution achievable without loss of immunoreactivity was three DTPA groups per immunoglobulin molecule. The resulting conjugate was labeled with {sup 111}In by brief incubation with {sup 111}InCl{sub 3}, giving a mean radiochemical yield of {sup 111}In-labeled antibody of 96%. The ({sup 111}In)B72.3 preparation was mixed with an ({sup 125}I) B72.3 preparation, obtained by the chloramine-T method, and the mixture administered to athymic mice bearing subcutaneous LS174T colon carcinoma xenografts. There were no significant differences (p greater than 0.1) in the biodistributions of the two labels at 1, 2, 5, and 7 days postinjection. These results are contrasted with prior studies showing elevated levels of {sup 111}In in liver, spleen, and kidneys using B72.3-DTPA conjugates prepared via the bicyclic anhydride. It is concluded that protein cross-linking and/or the formation of unstable chelate sites in anhydride coupled conjugates underlie these disparities.

  11. Dual isotope study of iodine-125 and indium-111-labeled antibody in athymic mice

    International Nuclear Information System (INIS)

    Carney, P.L.; Rogers, P.E.; Johnson, D.K.

    1989-01-01

    Monoclonal antibody B72.3 was coupled to a benzylisothiocyanate derivative of diethylenetriaminepentaacetic acid (DTPA). The maximum substitution achievable without loss of immunoreactivity was three DTPA groups per immunoglobulin molecule. The resulting conjugate was labeled with 111 In by brief incubation with 111 InCl 3 , giving a mean radiochemical yield of 111 In-labeled antibody of 96%. The [ 111 In]B72.3 preparation was mixed with an [ 125 I] B72.3 preparation, obtained by the chloramine-T method, and the mixture administered to athymic mice bearing subcutaneous LS174T colon carcinoma xenografts. There were no significant differences (p greater than 0.1) in the biodistributions of the two labels at 1, 2, 5, and 7 days postinjection. These results are contrasted with prior studies showing elevated levels of 111 In in liver, spleen, and kidneys using B72.3-DTPA conjugates prepared via the bicyclic anhydride. It is concluded that protein cross-linking and/or the formation of unstable chelate sites in anhydride coupled conjugates underlie these disparities

  12. Mathematical models for the study of the dynamics of indium-111-labelled platelets in idiopathic thrombocytopenic purpura

    International Nuclear Information System (INIS)

    Savolainen, S.

    1992-01-01

    Platelet kinetics in patients with idiopathic thrombocytopenic purpura (ITP) was investigated by applying various models (compartmental and open models, and functional and uptake analyses) to data on indium-111 labelled platelets monitored with a gamma camera following intravenous injection of labelled platelets. The usefulness of the selected models was tested by relating kinetic data to pathophysiological phenomena. A comparison of the results of platelet and colloid kinetics showed that the splenic platelet kinetics in ITP patients does not seem to be primarily dependent on the reticuloendothelial system. Although closed three-compartmental analysis seemed to be superior to the other models applied, none of the methods of analysis tested in this study appears to provide a complete description of short-lived platelet dynamics, as for every model certain assumptions that are not entirely relevant have to be made; this stresses the importance of combining various methods for a comprehensive analysis of a complex phenomenon. Conclusions concerning the function of biological systems should be based on more than one dynamic model or calculation method, since applying only one model (or calculation method) may give artifactual results due to poor statistics of observed data or to inexactness of the assumptions concerning the model

  13. Comparison of indium-111 octreotide and thalium-201 scintigraphy in patients mammographically suspected of having breast cancer: preliminary results

    International Nuclear Information System (INIS)

    Vural, G.; Uenlue, M.; Atasever, T.; Oezur, I.; Oezdemir, A.; Goekcora, N.

    1997-01-01

    Indium-111 octreotide and thallium-201 scintigraphic studies were compared in 21 patients (16 with palpable and five with non-palpable lesions) suspected of having breast malignancies on the basis of mammography. Early (15 min) and late (3 h) 201 Tl (111 MBq) and 4-h and 24-h 111 In-octreotide (111-148 MBq) static planar anterior images (matrix 256 x 256) were obtained on separate days. Images were evaluated both visually and quantitatively. Biopsy was performed following the imaging studies. Histopathology revealed 17 breast carcinomas (15 cases of invasive ductal carcinoma, one mucinous adenocarcinoma and one intraductal carcinoma) and four benign breast lesions (two fibroadenomas, one abscess and one case of fat necrosis). The means histopathological tumour size (mean largest diameter) was 3.38±1.9 cm. 111 In-octreotide detected 16 of the 17 breast cancers (94%) while 201 Tl detected 13 of them (76%). Both 111 In-octreotide and 201 Tl missed one nonpalpable carcinoma showing only an isolated cluster of microcalcifications on mammography. The smallest tumour size detected by both agents 1.5 x 1.5 cm. Of the four benign lesions, only the breast abscess revealed both 201 Tl and 111 In-octreotide uptake. 111 In-octreotide scan also showed tracer uptake in five of the six patients with histologically proven axiallary metastases, while four of these six patient showed 201 Tl uptake. (orig./VHE)

  14. Comparison of indium-111 octreotide and thalium-201 scintigraphy in patients mammographically suspected of having breast cancer: preliminary results

    Energy Technology Data Exchange (ETDEWEB)

    Vural, G. [Dept. of Nuclear Medicine, Faculty of Medicine, Gazi Univ., Ankara (Turkey); Uenlue, M. [Dept. of Nuclear Medicine, Faculty of Medicine, Gazi Univ., Ankara (Turkey); Atasever, T. [Dept. of Nuclear Medicine, Faculty of Medicine, Gazi Univ., Ankara (Turkey); Oezur, I. [Dept. of Radiology, Faculty of Medicine, Gazi Univ., Ankara (Turkey); Oezdemir, A. [Dept. of Radiology, Faculty of Medicine, Gazi Univ., Ankara (Turkey); Goekcora, N. [Dept. of Nuclear Medicine, Faculty of Medicine, Gazi Univ., Ankara (Turkey)

    1997-03-01

    Indium-111 octreotide and thallium-201 scintigraphic studies were compared in 21 patients (16 with palpable and five with non-palpable lesions) suspected of having breast malignancies on the basis of mammography. Early (15 min) and late (3 h) {sup 201}Tl (111 MBq) and 4-h and 24-h {sup 111}In-octreotide (111-148 MBq) static planar anterior images (matrix 256 x 256) were obtained on separate days. Images were evaluated both visually and quantitatively. Biopsy was performed following the imaging studies. Histopathology revealed 17 breast carcinomas (15 cases of invasive ductal carcinoma, one mucinous adenocarcinoma and one intraductal carcinoma) and four benign breast lesions (two fibroadenomas, one abscess and one case of fat necrosis). The means histopathological tumour size (mean largest diameter) was 3.38{+-}1.9 cm. {sup 111}In-octreotide detected 16 of the 17 breast cancers (94%) while {sup 201}Tl detected 13 of them (76%). Both {sup 111}In-octreotide and {sup 201}Tl missed one nonpalpable carcinoma showing only an isolated cluster of microcalcifications on mammography. The smallest tumour size detected by both agents 1.5 x 1.5 cm. Of the four benign lesions, only the breast abscess revealed both {sup 201}Tl and {sup 111}In-octreotide uptake. {sup 111}In-octreotide scan also showed tracer uptake in five of the six patients with histologically proven axiallary metastases, while four of these six patient showed {sup 201}Tl uptake. (orig./VHE)

  15. Comparison of indium 111 oxine-labeled platelet aggregation between sutured and argon laser-assisted vascular anastomoses

    International Nuclear Information System (INIS)

    Fujitani, R.M.; White, R.A.; Kopchok, G.E.; Vlasak, J.; Marcus, C.S.; White, G.H.

    1988-01-01

    The thrombogenicity of argon laser-assisted vascular anastomoses (LAVAs) was compared with that of sutured vascular anastomoses (SVAs) by measurement of platelet aggregation at the site of repair in a canine model. Sequential 1 cm longitudinal carotid and femoral arteriotomies (n = 80) or jugular and femoral phlebotomies (n = 80) were performed, with each vessel having two tandem, randomly positioned arteriotomies or phlebotomies separated by a 4 cm length of intact vessel. One incision was repaired by SVA with continuous 6-0 polypropylene sutures and the other by argon LAVA. For the laser fusions, argon laser energy was applied to the adventitial surface of the vessel with a 300 micron fiberoptic probe with 0.5 W power, 1100 joules per square centimeter energy fluence, and 150 second exposure per 1 cm length. The arterial and venous segments of SVAs and LAVAs and an equivalent length of normal vessel were harvested at 48 hours (n = 16, 16, 16), 2 weeks (n = 12, 12, 12), and 4 weeks (n = 12, 12, 12). Autologous indium 111 oxine-labeled platelets were injected intravenously 48 hours before removal of the vascular repairs and the radioactivity of the specimens was determined on removal with a NaI (T1) well-type scintillation counter. Anastomotic platelet adherence index (APAI) was calculated as the ratio of emissions of SVA or LAVA to normal reference vessel

  16. Quantitative evaluation of indium-111 (In-111) octreotide pituitary activity: Comparison in patient with and without pituitary tumors

    Energy Technology Data Exchange (ETDEWEB)

    Gupta, P.; Waxman, A.; Nguyen, K. [Cedars-Sinai Medical Center, Los Angeles, CA (United States)] [and others

    1995-05-01

    Indium 111 Octreotide is known to detect pituitary tumors. Variable low level pituitary activity has been reported in pts. with no demonstrable pituitary tumors. To our knowledge, there have been no studies which quantitatively categorize pituitary activity with respect to distinguishing normal subject from pts. with pituitary tumors. 13 pts. with proven, treated acromegaly were included, as well as 15 pts. with no history of pituitary disorder. Both groups underwent SPECT In-111 scintigraphy 24 hours post-injection Average count per pixel ratios were obtained for the pituitary/calvarium (P/C) and pituitary/brain (P/B) regions. 10 pts. with acromegaly underwent growth hormone (GH) measurements 2 hours post-glucose load. Statistical correlation between growth hormone levels using P/C and P/B ratios were obtained. P/C ratios, as well as P/B ratios demonstrated high correlation with serum GH levels correlation coefficient(r)= .717 for P/C p<0.05, and correlation coefficient(r) = 0.828 for P/B ratios p<0.005. P/C ratios and P/B ratios for controls correlated closely with the upper level of normal predicted by P/C or P/B ratios as a function of serum growth hormone found in patients with acromegaly. Somatostatin receptor SPECT scintigraphy of the pituitary and appropriate quantitation can predict patients with growth hormone secreting tumors.

  17. Indium-111 labeling of leukocytes: a detrimental effect on neutrophil and lymphocyte function and an improved method of cell labelling

    International Nuclear Information System (INIS)

    Segal, A.W.; Deteix, P.; Garcia, R.; Tooth, P.; Zanelli, G.D.; Allison, A.C.

    1978-01-01

    A technique for the labeling of cells with the gamma emitter indium-111 has recently been developed. In this study the effects of the labeling procedure on some in vitro functions of human neutrophils and lymphocytes were investigated. With the standard labeling procedure, neutrophil chemotaxis was reduced to approximately 50% of normal and lymphocytes lost surface receptors and failed to respond to stimulation with phytohemagglutinin. The 8-hydroxyquinoline that is used to chelate the indium is toxic to lymphocytes; accordingly the relationship between the quantity of oxine, the chelation of indium, and cell labeling were investigated. Optimal conditions for In-111 cell labeling were established: 100 million cells in 10 ml Hanks' balanced salt solution are mixed with 5 μg of oxine in a mixture of 50 μl of ethanol and 200 μl of saline; they are incubated at 37 0 C for 10 min and then washed. Initially, neutrophils and lymphocytes appear functionally normal, but after 24 to 48 hr lymphocyte function is impaired as a result of radiation damage. This toxicity may limit studies by external scanning on the distribution and kinetics of lymphocytes labeled with In-111

  18. Breast cancer staqging using technitium-99m sestamibi and indium-111 pentetreotide single-photon emission tomography

    International Nuclear Information System (INIS)

    Chiti, A.; Agresti, R.; Maffioli, L.S.; Tomasic, G.; Savelli, G.; Crippa, F.; Pilotti, S.; Greco, M.; Bombardieri, E.

    1997-01-01

    We evaluated the clinical usefulness of single-photon emission tomography (SPET) with technetium-99m sestamibi and indium-111 pentetrotide in breast cancer staging. Fifteen patients with clinical and/or mammographic findings suggesting Tl-2N0-l breast cancer were studied. SPET images were acquired 20 min after 99m Tc-sestamibi injection and 4 and 24 h after 111 In-pentetreotide injection. Patients underwent surgery the day after the later 111 In-pentetrotide acquisition. Pathological examination showed 16 tumours in the 15 patients, with one bilateral carcinoma. The mean tumour diamter was 18.7 mm. Metastatic axillary involment was found in 6/16 tumours, with a mean of five metastatic nodes per axillary node involment. Both tracers correctly identified 15/16 primary tumours and five of the six cases of metastatic axillary node involvement. No difference between the tracers was observed in breast cancer staging. 99m Tc-sestamibi seems to the better tracer in terms of physical characteristics, execution time and cost-effectivness. Our data suggest the future possibility of using nuclear medicine imaging to avoid axillary dissection in patiens with Tl breast cancer

  19. The effect of ibuprofen on accumulation of indium-111-labeled platelets and leukocytes in experimental myocardial infarction

    International Nuclear Information System (INIS)

    Romson, J.L.; Hook, B.G.; Rigot, V.H.; Schark, M.A.; Swanson, D.P.; Lucchesi, B.R.

    1982-01-01

    To assess the ability of ibuprofen to influence the extent of platelet aggregation and leukocyte infiltration during acute myocardial infarction, autologous indium-111 ( 111 In)-labeled platelets or leukocytes were injected before 60 minutes of left circumflex coronary artery (LCx) occlusion, followed by 24 hours of reperfusion in the canine heart. Myocardial infarct size, as a percent of the area at risk, was reduced in the ibuprofen-treated group (12.5 mg/kg i.v. every 4 hours beginning 30 minutes before LCx occulsion) by 40%, from 48 +/- 4% in control animals to 29 +/- 4% in ibuprofen-treated dogs (p=0.005). Quantification of the platelet-associated 111 In radioactivity in irreversibly injured myocardium indicated that ibuprofen did not alter the accumulation of platelets in infarcted myocardium. In contrast, leukocyte accumulation in infarcted tissue was reduced significantly. In tissue samples with 0.41-0.60 gram infarct, the infarcted/normal ratio of leukocyte radioactivity was 12 +/- 2 in control dogs and 4 +/- 1 in ibuprofen-treated dogs, which represents a 67% reduction in leukocyte accumulation in ibuprofen-treated compared with control dogs. Similar reductions were found in other gram-infarct-weight categories. Although both platelets and leukocytes acumulate in infarcted canine myocardium, ibuprofen may exert its beneficial effect on ischemic myocardium by suppressing the inflammatory response associated with myocardial ischemia and infarction

  20. Optimum allocation of imaging time and minimum detectable activity in dual isotope blood pool subtraction indium-111 platelet imaging

    International Nuclear Information System (INIS)

    Machac, J.; Horowitz, S.F.; Goldsmith, S.J.; Fuster, V.

    1984-01-01

    Indium-111 labeled platelet imaging is a tool for detection of thrombus formation in vascular spaces. Dual isotope blood pool subtraction may help differentiate focal platelet accumulation from blood pool activity. This study used a computer model to calculate the minimum excess-to-blood pool platelet ratio (EX/BP) and the optimum dual isotope imaging times under varied conditions of lesion size. The model simulated usual human imaging doses of 500 μCi of In-111 platelets and 5mCi of Tc-99m labeled RBCs giving a reference cardiac blood pool region (100cc) of 10000 cpm for Tc-99m and 500 cpm for In-111. The total imaging time was fixed at 20 minutes, while the two isotope imaging times (TIn/TTc) were varied, as were the simulated lesion size (cc) and EX/BP. The relative error of the excess counts was calculated using propagation of error theory. At the critical level of detection, where the excess lesion counts equal 3 times the standard deviation, the optimum TIn/TTc and minimum Ex/BP were determined for each lesion size. For the smallest lesion size (0.1cc), the minimum detectable EX/BP ratio was 1.6, with the best TIn/TTC ratio of 18/2 minutes, and for large lesions, an EX/BP of 0.1, with a TIn/TTc of 16/4. This model provides an estimate of the sensitivity and optimizes imaging times in dual isotope subtraction platelet imaging. The model is adaptable to varying isotope doses, total imaging times and lesion size. This information will be helpful in future in- vivo imaging studies of intravascular thrombi in humans

  1. Indium-111-labeled platelets: effect of heparin on uptake by venous thrombi and relationship to the activated partial thromboplastin time

    International Nuclear Information System (INIS)

    Fedullo, P.F.; Moser, K.M.; Moser, K.S.; Konopka, R.; Hartman, M.T.

    1982-01-01

    The goal of heparin thepapy in deep vein thrombosis is to prevent thrombus extension. The relationship between thrombus extension and the results of coagulation tests used to monitor heparin thepapy is unclear. To expose this relationship, we studied the effect of several heparin regimens on the accretion of indium-111-labeled platelets on fresh venous thrombi, as detected by gamma imaging, and monitored the activated partial thromboplastin time (APTT). Six dogs were treated with a 300-U/kg bolus of heparin followed by a 90-U/kg/hour heparin infusion, a dose of heparin sufficient to increase the APTT to levels greater than eight times baseline (APTT ratio); platelet accretion (thrombus imaging) occurred only after the heparin effect was reversed with protamine sulfate. Nineteen dogs were treated with a 150-U/kg bolus of heparin followed by a 4-hour, 45-U/kg/hour heparin infusion; a thrombus was demonstrated only after protamine injection in 12 (mean APTT ratio 1.3 +/- 0.19) and before protamine injection in seven. In thirteen of these 19 dogs, 30 minutes separated the platelet injection from heparin therapy, while in six this duration was less than 30 minutes. In four of these six dogs, thrombi were demonstrated before protamine therapy and at APTT ratios greater than 3.0. Finally, 10 dogs were treated with a 100-U/kg bolus followed by a 3-hour, 50-U/kg/hour heparin infusion, after which the APTT was allowed to return to baseline values spontaneously. In all 10 dogs, a thrombus was demonstrated only after cessation of the heparin infusion, and at a mean APTT ratio of 1.4 +/- 0.15 times baseline. These results suggest that, except with very early platelet injection, platelet accretion by thrombi is consistently inhibited by heparin at APTT ratios greater than 2.5

  2. Clinical validation of the avidin/indium-111 biotin approach for imaging infection/inflammation in orthopaedic patients

    International Nuclear Information System (INIS)

    Lazzeri, E.; Molea, N.; Bodei, L.; Bianchi, R.; Manca, M.; Marchetti, S.; Consoli, V.; Chinol, M.; Paganelli, G.; Mariani, G.

    1999-01-01

    We report here the results of a validation study of the avidin/indium-111 biotin approach in patients with skeletal lesions. This study involved 54 patients with orthopaedic conditions: 20 patients with intermediate suspected osteomyelitis of the trunk, 19 patients with infection/inflammation of prosthetic joint replacements, and 15 patients with suspected osteomyelitis of appendicular bones. Avidin (3 mg) was injected as an i.v. bolus, followed 4 h later by 111 In-biotin; imaging was acquired 30 min and 16-18 h after administration of 111 In-biotin. Technetium-99m hexamethylpropylene amine oxime ( 99m Tc-HMPAO)-labelled leucocyte scintigraphy was performed in 39/54 patients. The overall sensitivity of the avidin/ 111 In-biotin scan was 97.7% (versus 88.9% for 99m Tc-HMPAO leucocyte scintigraphy). While the diagnostic performance of avidin/ 111 In-biotin scintigraphy was similar to that of 99m Tc-HMPAO leucocyte scintigraphy in patients with prosthetic joint replacements or osteomyelitis of appendicular bones, the avidin/ 111 In-biotin approach clearly performed better than 99m Tc-HMPAO leucocyte scintigraphy in patients with suspected osteomyelitis of the trunk (100% sensitivity, specificity and accuracy versus 50% sensitivity, 100% specificity and 66.7% accuracy for 99m Tc-HMPAO-leucocyte scintigraphy). These results demonstrate the feasibility of the avidin/ 111 In-biotin approach for imaging sites of infection/inflammation in the clinical setting. Although no systematic advantages of avidin/ 111 In-biotin scintigraphy were found versus 99m Tc-HMPAO leucocyte scintigraphy, the newer scintigraphic method is more practicable and involves lower biological risk for the operators. (orig.)

  3. Clinical validation of the avidin/indium-111 biotin approach for imaging infection/inflammation in orthopaedic patients

    Energy Technology Data Exchange (ETDEWEB)

    Lazzeri, E.; Molea, N.; Bodei, L.; Bianchi, R. [Regional Centre of Nuclear Medicine, University of Pisa, Pisa (Italy); Manca, M.; Marchetti, S.; Consoli, V. [Institute of Orthopedics, University of Pisa, Pisa (Italy); Chinol, M.; Paganelli, G. [Nuclear Medicine Service, European Institute of Oncology, Milan (Italy); Mariani, G. [Nuclear Medicine Service, DIMI, University of Genoa, Genoa (Italy)

    1999-06-01

    We report here the results of a validation study of the avidin/indium-111 biotin approach in patients with skeletal lesions. This study involved 54 patients with orthopaedic conditions: 20 patients with intermediate suspected osteomyelitis of the trunk, 19 patients with infection/inflammation of prosthetic joint replacements, and 15 patients with suspected osteomyelitis of appendicular bones. Avidin (3 mg) was injected as an i.v. bolus, followed 4 h later by {sup 111}In-biotin; imaging was acquired 30 min and 16-18 h after administration of {sup 111}In-biotin. Technetium-99m hexamethylpropylene amine oxime ({sup 99m}Tc-HMPAO)-labelled leucocyte scintigraphy was performed in 39/54 patients. The overall sensitivity of the avidin/{sup 111}In-biotin scan was 97.7% (versus 88.9% for {sup 99m}Tc-HMPAO leucocyte scintigraphy). While the diagnostic performance of avidin/{sup 111}In-biotin scintigraphy was similar to that of {sup 99m}Tc-HMPAO leucocyte scintigraphy in patients with prosthetic joint replacements or osteomyelitis of appendicular bones, the avidin/{sup 111}In-biotin approach clearly performed better than {sup 99m}Tc-HMPAO leucocyte scintigraphy in patients with suspected osteomyelitis of the trunk (100% sensitivity, specificity and accuracy versus 50% sensitivity, 100% specificity and 66.7% accuracy for {sup 99m}Tc-HMPAO-leucocyte scintigraphy). These results demonstrate the feasibility of the avidin/{sup 111}In-biotin approach for imaging sites of infection/inflammation in the clinical setting. Although no systematic advantages of avidin/{sup 111}In-biotin scintigraphy were found versus {sup 99m}Tc-HMPAO leucocyte scintigraphy, the newer scintigraphic method is more practicable and involves lower biological risk for the operators. (orig.) With 3 figs., 2 tabs., 56 refs.

  4. Relative quantification of indium-111 pentetreotide and gallium-68 DOTATOC uptake in the thyroid gland and association with thyroid pathologies.

    Science.gov (United States)

    Lincke, Thomas; Singer, Joerg; Kluge, Regine; Sabri, Osama; Paschke, Ralf

    2009-04-01

    Recent data suggest that increased somatostatin receptor (SSTR) expression is detectable in several thyroid diseases. This raises the question as to the specificity and pathophysiologic relevance of these findings. Therefore, we systematically evaluated Indium-111 (In-111) pentetreotide scintigraphies and Gallium-68 (Ga-68) DOTA-Phe(1)-Tyr(3)-Octreotide (DOTATOC) positron emission tomography (PET) scans for thyroid radiotracer uptake. Relative binding of In-111 pentetreotide in the thyroid was measured by region of interest (ROI) technique in 4-hour and 24-hour post-injection (p.i.) planar images of 73 patients undergoing In-111 pentetreotide scintigraphy. Ga-68 DOTATOC PET scans of 77 patients were analyzed by ROI technique applied to coronal slices of 1 cm (0.39 inch) thickness with highest uptake in the thyroid region. A basal indium In-111 and Ga-68 DOTATOC uptake was found in normal thyroid glands. Hot nodules, disseminated thyroid autonomy, and most cases of active Hashimoto's disease as well as goiters and nodular thyroids showed increased In-111 pentetreotide and/or Ga-68 DOTATOC uptake. Higher relative In-111 pentetreotide uptake in the 24-hour p.i. images as compared to the 4-hour p.i. images except for patients after thyroidectomy indicates specific receptor binding in the thyroid. The increased In-111 pentetreotide and Ga-68 DOTATOC uptake in active Hashimoto's disease is most likely related to the lymphocytic infiltration of the thyroid. However, the physiologic or pathophysiologic relevance of the increased In-111 pentetreotide and Ga-68 DOTATOC uptake in normal thyroid glands, hot and cold nodules, and goiters and nodular thyroids remain to be determined.

  5. Sequential functional imaging with technetium-99m hexakis-2-methoxyisobutylisonitrile and indium-111 octreotide: can we predict the response to chemotherapy in small cell lung cancer?

    International Nuclear Information System (INIS)

    Moretti, J.L.; Caglar, M.; Boaziz, C.; Caillat-Vigneron, N.; Morere, J.F.

    1995-01-01

    A case of small cell lung carcinoma (SCLC) demonstrating uptake on functional indium-111 octreotide scintigraphy is presented. Technetium-99m hexakis-2-methoxyisobutylisonitrile (MIBI) scintigraphy clearly delineated an absence of radionuclide uptake at the tumour site. This suggested the presence of multidrug resistance-mediated P glycoprotein (Pgp) on tumour cells, which recognizes certain chemotherapeutic agents as well as MIBI as a substrate and avoids radionuclide concentration. Following three courses of chemotherapy, the patient failed to improve and eventually died. This case demonstrates the importance of functional images, which have the potential to predict the outcome in response to chemotherapy. (orig.)

  6. In vitro comparison of renal handling and uptake of two somatostatin receptor-specific peptides labeled with indium-111

    International Nuclear Information System (INIS)

    Trejtnar, F.; Novy, Z.; Petrik, M.; Laznickova, A.; Melicharova, L.; Vankova, M.; Laznicek, M.

    2008-01-01

    Radiolabeled receptor-specific somatostatin analogs labeled with gamma- or beta-emitting radionuclides are useful for scintigraphic imaging and/or therapy of selected neuroendocrine tumors. However, significant renal uptake may result in radiotoxicological injury of the kidney and can limit clinical application of the agents. The aim of the study was to analyze renal handling, rate, and mechanism of renal accumulation of two somatostatin receptor-targeted peptides, [DOTA 0 , Tyr 3 , Thr 8 ]-octreotide (DOTA-TATE) and [DOTA 0 , 1-Nal 3 ]-octreotide (DOTA-NOC), labeled with indium-111 using in vitro methods. The perfused rat kidney and freshly isolated rat renal cells were used as experimental models. The perfusion was performed in a recirculation regimen at constant pressure with solution containing bovine albumin, erythrocytes, and a mixture of essential substrates. The renal cells were isolated from rat kidneys using two-phase collagenase perfusion. Accumulation studies were used to evaluate the renal uptake of the peptides and to compare their accumulation with that of passively or actively transported model drugs. The influence of selected inhibitors of receptor-mediated endocytosis and the inhibition of energy-dependent transport processes on the uptake were also investigated using isolated renal cells. The renal clearance of 111 In-DOTA-NOC in the perfused rat kidney was significantly lower than that of 111 In-DOTA-TATE. Reverse situation was found in the case of renal retention. Pretreatment of the perfused kidney with maleate markedly decreased the renal retention. 111 In-DOTA-NOC was accumulated in the isolated renal cells at a higher rate than 111 In-DOTA-TATE (ratio 3:1). The uptake of the radiopeptides in renal cells was higher than the uptake of not only the passively transported sucrose but also actively transported and accumulated methylglucose. The rank order of potency to inhibit the uptake by active endocytosis was approximately aprotinin

  7. Indium 111. Radiation protection

    International Nuclear Information System (INIS)

    Grafstroem, G.; Joensson, B.A.; Strand, S.E.

    1989-01-01

    The radiopharmaceutucal 111 In-oxine is used in labelling of different blood cells and proteins. Due to its liquid state, there is always a risk for contamination during handling procedures. The aim of the project was to evaluate the contamination risks, when using this radiopharmaceutical. The investigation includes calculations of the absorved dose to the skin after a contamination of 111 In-oxine, including the radionuclide impurity 114 In m / 114 In. Investigations of 288 protection gloves shows that there is always a risk for contamination, when working with 111 In-oxine. On the protection gloves, we found activities normally ranging from a 100 Bq up to a few kBq. Noticeable is the contamination on the vials, already before their use. Besides 111 In we found most of the radionuclides used in nuclear medicine, with activities up to tens of kBq. The radionuclide impurity was cleary detectable but below the recommended value. The penetration of 111 In-oxine protection gloves of latex was negligible. Measurements of penetration in skin was evaluated with two independent methods; in vivo using a surface barrier detector, and by autoradiography. The measured penetration was less than a few micrometers. Calculation from the experimental contamination values show that the absorbed dose to the basal cell layer could be in order of several Gy. (authors)

  8. Effects of antithrombotic drugs in patients with left ventricular thrombi: assessment with indium-111 platelet imaging and two-dimensional echocardiography

    International Nuclear Information System (INIS)

    Stratton, J.R.; Ritchie, J.L.

    1984-01-01

    Patients with left ventricular thrombi not caused by recent myocardial infarction were prospectively studied by indium-111 platelet imaging and two-dimensional echocardiography to determine the reproducibility of these techniques and the short-term effects of sulfinpyrazone (200 mg four times daily), aspirin (325 mg three times daily) plus dipyridamole (75 mg three times daily), and full-dose warfarin. At baseline, all patients underwent indium-111 platelet imaging and echocardiography, and the results were positive for thrombus. In six patients on no antithrombotic drug therapy, repeat platelet scans and echocardiographic studies at 6.0 +/- 3.3 weeks remained positive and were unchanged. In seven patients studied on sulfinpyrazone, three platelet scans became negative, two became equivocal, and two were unchanged; the presence and size of thrombus was constant by echocardiography in all seven patients. Of the six patients studied on aspirin plus dipyridamole, one platelet scan became negative, those of three became equivocal, and two were unchanged; all echocardiographic findings remained positive, but one patient had decreased thrombus size. Among four warfarin-treated patients, three had resolution of platelet deposition and one was unchanged; by echocardiography, thrombus resolved in one patient, was decreased in size in one, and was unchanged in two. We conclude that, in the absence of antithrombotic drug therapy, platelet imaging and echocardiographic findings are stable in patients with left ventricular thrombi not caused by recent myocardial infarction. Sulfinpyrazone, aspirin plus dipyridamole, and warfarin all interrupt platelet deposition in some patients with chronic left ventricular thrombi

  9. Increased blood clearance rate of indium-111 oxine-labeled autologous CD4+ blood cells in untreated patients with Hodgkin's disease

    International Nuclear Information System (INIS)

    Grimfors, G.; Holm, G.; Mellstedt, H.; Schnell, P.O.; Tullgren, O.; Bjoerkholm, M.

    1990-01-01

    Untreated patients with Hodgkin's disease (HD) have a blood T-lymphocytopenia mainly caused by a reduction of the CD4+ subset. Indirect support for a sequestration of T cells in the spleen and tumor-involved lymphoid tissue has accumulated. To test the hypothesis that the blood CD4 T-lymphocytopenia in patients with HD is caused by an altered lymphocyte traffic, 12 untreated HD patients and five in complete clinical remission (CCR) were studied. Blood lymphocytes were collected by leukapheresis and gradient centrifugation, and were further purified by an adherence step. The cells were labeled with indium-111 oxine and reinfused intravenously into the patient. The radioactivity of CD4+ and CD8+ blood lymphocytes separated by immunoabsorption was measured from serial blood samples. CD4+ cells were eliminated more rapidly in untreated patients than patients in CCR. Repeated gamma camera imaging after autotransfusion of indium-111 oxine labeled cells demonstrated an accumulation of radioactivity in tumor-involved tissue of untreated patients. These findings support the concept of an enhanced elimination of CD4+ cells in patients with active HD that may contribute to the observed blood T-lymphocytopenia and may reflect a biologic response to the tumor

  10. The use of indium-111 labeled platelet scanning for the detection of asymptomatic deep venous thrombosis in a high risk population

    International Nuclear Information System (INIS)

    Siegel, R.S.; Rae, J.L.; Ryan, N.L.; Edwards, C.; Fortune, W.P.; Lewis, R.J.; Reba, R.C.

    1989-01-01

    Five hundred indium-111 labeled platelet imaging studies (387 donor and 113 autologous) were performed postoperatively in 473 patients who had undergone total hip replacement, total knee replacement, or internal fixation of a hip fracture to detect occult deep venous thrombosis. All patients had been anticoagulated prophylactically with aspirin, warfarin sodium (Coumadin), or dextran. Thirty-four possible cases of proximal deep venous thrombosis were identified in 28 asymptomatic patients. To verify the scan results, 31 venograms were performed in 25 patients (three refused). In 21 of 31 cases, totally occlusive thrombi were detected; in 5 cases, partially occlusive thrombi were detected; in 5 cases, no thrombus was seen. No patient who had a negative scan nor any patient who had a verified positive scan (and received appropriate heparin therapy) subsequently developed symptoms or signs of pulmonary embolism. One hundred forty-one indium study patients also underwent Doppler ultrasonography/impedance plethysmography (Doppler/IPG) as a comparative non-invasive technique. In 137 cases, the results of the indium study and Doppler/IPG studies were congruent. The indium study had no false negative results that were detected by Doppler/IPG. No patient had any clinically evident toxicity. These results suggest that indium-111 labeled platelet scanning is a safe, noninvasive means for identifying DVT in high risk patients

  11. Study of the viability of technetium-99m labeling of whole antimyosin antibody and its fragment: development of radiopharmaceutical for cardiac survey

    International Nuclear Information System (INIS)

    Carvalho, Guilherme Luiz de Castro

    2007-01-01

    In the acute myocardium infarction, the myocytes cell membrane loses its integrity, allowing the influx of extracellular macromolecules such as circulating antibody into the damaged cell. The use of the specific antibodies against cardiac myosin labeled with 99m Tc allows to determine the localization and extension of myocardial infarction. The purpose of this work was to study the viability of labeling of the antimyosin monoclonal antibody and its fragment F(ab')2 with 99m Tc. Because of the high cost of antimyosin antibody, others antibodies were used to optimize the methodology and the best condition was used for antimyosin antibody. The intact antibody was cleaved by pepsin to produce F(ab') 2 fragment. The F(ab') 2 and the intact antibody were reduced by treatment with Dithiothreitol (DTT) and 2-Mercaptoethanol (2-ME) and labeled with 99m Tc by direct method. Different concentrations of reductant, mixing conditions and incubation times were studied. In the standard condition, incubation at molar ratio 1:1000 (antibody:reducing agent) at room temperature for 30 minutes with continuous rotation (850 rpm), 13.28 - SH groups were formed per molecule. It was studied the influence of p H, of the concentration of stannous chloride (Sn 2+ ) and incubation time in the labeling condition. The better radiochemical yield (90.06 +- 1.53%) was obtained using 2.5 μg of Sn 2+ in p H 4.5 for 60 minutes. The labeling of the fragment F(ab') 2 did not present satisfactory results because of the low yield of the digestion. After purification by PD-10, the biodistribution study was performed and showed that the intact antimyosin antibody labeled with 99m Tc presented fast kinetic compatible with the biodistribution of an intact antibody labeled with 99m Tc. Scintigraphy image of the animal with myocardial infarction was obtained and compared with the image of a normal animal. The studies allow to conclude that the use of fragment F(ab') 2 are not viable, but the use of the labeled

  12. In vitro and in vivo properties of human/mouse chimeric monoclonal antibody specific for common acute lymphocytic leukemia antigen

    International Nuclear Information System (INIS)

    Saga, T.; Endo, K.; Koizumi, M.; Kawamura, Y.; Watanabe, Y.; Konishi, J.; Ueda, R.; Nishimura, Y.; Yokoyama, M.; Watanabe, T.

    1990-01-01

    A human/mouse chimeric monoclonal antibody specific for a common acute lymphocytic leukemia antigen was efficiently obtained by ligating human heavy-chain enhancer element to the chimeric heavy- and light-chain genes. Cell binding and competitive inhibition assays of both radioiodine and indium-111- (111In) labeled chimeric antibodies demonstrated in vitro immunoreactivity identical with that of the parental murine monoclonal antibodies. The biodistribution of the radiolabeled chimeric antibody in tumor-bearing nude mice was similar to that of the parental murine antibody. Tumor accumulation of radioiodinated parental and chimeric antibodies was lower than that of 111 In-labeled antibodies, probably because of dehalogenation of the radioiodinated antibodies. Indium-111-labeled chimeric antibody clearly visualized xenografted tumor. These results suggest that a human/mouse chimeric antibody can be labeled with 111 In and radioiodine without the loss of its immunoreactivity, and that chimeric antibody localizes in vivo in the same way as the parental murine antibody

  13. PHARMACOKINETICS AND SCINTIGRAPHY OF INDIUM-111-DTPA-MOC-31 IN SMALL-CELL LUNG-CARCINOMA

    NARCIS (Netherlands)

    KOSTERINK, JGW; DEJONGE, MWA; SMIT, EF; PIERS, DA; KENGEN, RAM; POSTMUS, PE; SHOCHAT, D; GROEN, HJM; THE, HT; DELEIJ, L

    1995-01-01

    Radiolabeled MOC-31 retains its immunoreactivity and shows good in vivo immunolocalization to human SCLC xenografted in nude rats. Methods: We evaluated the immunotargeting properties and safety of In-111-labeled monoclonal antibody (MAb) MOC-31 (125 MBq, 5 mg) in six patients with histologically

  14. Comparison of oral iodine-131-cellulose and indium-111-DTPA as tracers for colon transit scintigraphy: Analysis by colon activity profiles

    International Nuclear Information System (INIS)

    Smart, R.C.; McLean, R.G.; Gaston-Parry, D.; Barbagallo, S.; Bruck, C.E.; King, D.W.; Lubowski, D.Z.; Talley, N.A.

    1991-01-01

    In 11 normal subjects and 11 patients with a clinical diagnosis of constipation, oral 131I-cellulose and 111In-DTPA were compared simultaneously as tracers for radionuclide colon transit scintigraphy. Visual assessment of the images revealed no differences between tracers. Quantitation was performed using total and segmental percent retention and the derived value of clearance half-time. In addition, profiles of the activity distribution along the length of the colon were generated and the mean position of the activity in the colon calculated. For all indices, the results were similar in both normal subjects and constipated patients when comparing tracers, although marked differences were present between normal subjects and constipated patients for each tracer. Indium-111-DTPA was easy to administer and dosimetry was more acceptable than for 131I-cellulose, especially in constipated patients. It is concluded that 111In-DTPA is the preferred tracer for oral colon transit scintigraphy

  15. Total-hip arthroplasty: Periprosthetic indium-111-labeled leukocyte activity and complementary technetium-99m-sulfur colloid imaging in suspected infection

    International Nuclear Information System (INIS)

    Palestro, C.J.; Kim, C.K.; Swyer, A.J.; Capozzi, J.D.; Solomon, R.W.; Goldsmith, S.J.

    1990-01-01

    Indium-111-labeled leukocyte images of 92 cemented total-hip arthroplasties were correlated with final diagnoses. Prostheses were divided into four zones: head (including acetabulum), trochanter, shaft, and tip. The presence (or absence) and intensity of activity in each zone was noted, and compared to the corresponding contralateral zone. Though present in all 23 infected arthroplasties, periprosthetic activity was also present in 77% of uninfected arthroplasties, and was greater than the contralateral zone 51% of the time. When analyzed by zone, head zone activity was the best criterion for infection (87% sensitivity, 94% specificity, 92% accuracy). Fifty of the arthroplasties were studied with combined labeled leukocyte/sulfur colloid imaging. Using incongruence of images as the criterion for infection, the sensitivity, specificity, and accuracy of the study were 100%, 97%, and 98%, respectively. While variable periprosthetic activity makes labeled leukocyte imaging alone unreliable for diagnosing hip arthroplasty infection, the addition of sulfur colloid imaging results in a highly accurate diagnostic procedure

  16. Use of Take-set system for radiopharmaceutical labelling: example of indium-111 labeled pentetreotide (Octreoscan) preparation; Utilisation du systeme Take-set pour le radiomarquage des medicaments radiopharmaceutiques: exemple de la preparation du pentetreotide marque a l'indium 111 (Octreoscan)

    Energy Technology Data Exchange (ETDEWEB)

    Ben Reguiga, M.; Sinegre, M. [Hopital Beaujon, Unite de Radiopharmacie, Service de Pharmacie-toxicologie, 92 - Clichy (France); Besse, H.; Stievenart, J.L.; Le Guludec, D. [Hopital Beaujon, Service de Medecine Nucleaire92 - Clichy (France)

    2009-09-15

    The quality of indium 111 radiolabelled pentetreotide preparation (Octreoscan, Covidien) depends on several factors among which the use of a special transfer needle (Sterican) especially conceived to avoid the metal impurities introduction into the reactional medium during labelling. This device, usually provided by the supplier, can exceptionally present defects (twisted needle, folded bevel...) preventing its use for the preparation. In order to manage this risk, we propose in the present technical note an alternative labelling method, based on an adaptation of the original one and using another transfer device, the Take-setSWAN system, which permits to obtain high quality Octreoscan preparations that meet the product approval specifications. (authors)

  17. 111In antimyosin uptake in skeletal muscle: case report and literature review

    International Nuclear Information System (INIS)

    Alberini, J.L.; Bourguet, P.

    1999-01-01

    We report an observation of skeletal muscle uptake on antimyosin imaging. Aim of this imaging was to identify recent myocardial infarction in a patient resuscitated after cardio-version. Planar anterior and Left Anterior Oblique (45 deg. and 70 deg.) views centered on the thorax were performed 48 hours after injection of In-111 antimyosin. This uptake could be explained by a muscle necrosis, induced by the electroshock. Similar cases were reported with Tc-99m pyrophosphate. It must be remind on one hand the importance to perform several incidences for planar images and SPET and on the other hand the potential utility of antimyosin antibody imaging in skeletal muscle disorders. (authors)

  18. Targeting of indium 111-labeled bivalent hapten to human melanoma mediated by bispecific monoclonal antibody conjugates: Imaging of tumors hosted in nude mice

    International Nuclear Information System (INIS)

    Le Doussal, J.M.; Gruaz-Guyon, A.; Martin, M.; Gautherot, E.; Delaage, M.; Barbet, J.

    1990-01-01

    Antibody conjugates were prepared by coupling F(ab')2 or Fab' fragments of an antibody specific for the human high molecular weight-melanoma associated antigen to Fab' fragments of an antibody specific for indium-diethylenetriaminepentaacetate complexes. Monovalent and bivalent haptens were synthesized by reacting the dipeptide tyrosyl-lysine with diethylenetriaminepentaacetic cyclic anhydride. In vitro, the antibody conjugate mediated binding of the 111In-labeled haptens to melanoma cells. In vivo, it allowed specific localization of the haptens in A375 tumors. The bivalent hapten exhibited much higher efficiency at targeting 111In onto cells, both in vitro and in vivo. Antibody conjugate and hapten doses (2 micrograms and 1 pmol, respectively) and the delay between antibody conjugate and tracer injections (24 h) were adjusted to maximize tumor uptake (4% injected dose/g) and tumor to normal tissue contrast (greater than 3) obtained 3 h after injection of the 111In-labeled bivalent hapten. This two-step technique, when compared to direct targeting of 111In-labeled F(ab')2 fragments, provided lower localization of injected activity into the tumor (x 0.25), but higher tumor/tissue ratios, especially with respect to liver (x 7), spleen (x 8), and kidneys (x 10). In addition, high contrast images were obtained within 3 hours, instead of days. Thus, antibody conjugate-mediated targeting of small bivalent haptens, labeled with short half-life isotopes, is proposed as a general method for improving tumor radioimmunolocalization

  19. Scintigraphic detection of metastatic melanoma using indium 111/DTPA conjugated anti-gp240 antibody (ZME-018)

    International Nuclear Information System (INIS)

    Kirkwood, J.M.; Neumann, R.D.; Zoghbi, S.S.; Ernstoff, M.S.; Cornelius, E.A.; Shaw, C.; Ziyadeh, T.; Fine, J.A.; Unger, M.W.

    1987-01-01

    We evaluated the toxicity, pharmacokinetics, and localization of a monoclonal IgG2 alpha murine anti-human melanoma (gp240) antibody (ZME-018) that recognizes a tumor-associated cell surface glycoprotein of 240,000 molecular weight present in most melanomas. The antibody was conjugated with DTPA (diethylenetriamine pentaacetic acid) and labeled by chelation of 111 In. One mg of antibody labeled with 5 mCi of 111 In was infused, together with 0 to 40 mg of cold carrier ZME-018. The blood clearance, urinary excretion, and in vivo localization were determined in 26 patients. Scintigraphic images were obtained at 24 hours and 72 hours in all patients. Mild toxicity occurred in one patient. The half-time clearance of labeled monoclonal murine antibody (MoAb) from the blood increased from 16.1 hours at an antibody dose of 1 mg to 35.9 hours at 40 mg. Males showed faster clearance from the blood than did females or a single castrated male, perhaps due to selective concentration of antibody in the testes. Nonspecific uptake in liver, spleen, bone marrow, and intestine was seen in all patients. The percentage of known metastatic foci detected increased with the total dosage of antibody, from 23% at doses less than or equal to 5 mg, to 65%, 87% and 78% for 10, 20, and 40 mg, respectively. We conclude that at doses of greater than or equal to 10 mg, ZME-018 is a safe and potentially useful agent for the scintigraphic detection of metastatic malignant melanoma

  20. In vivo quantitation of platelet deposition on human peripheral arterial bypass grafts using indium-111-labeled platelets. Effect of dipyridamole and aspirin

    International Nuclear Information System (INIS)

    Pumphrey, C.W.; Chesebro, J.H.; Dewanjee, M.K.; Wahner, H.W.; Hollier, L.H.; Pairolero, P.C.; Fuster, V.

    1983-01-01

    Indium-111-labeled autologous platelets, injected 48 hours after operation, were used to evaluate the thrombogenicity of prosthetic material and the effect of platelet inhibitor therapy in vivo. Dacron double-velour (Microvel) aortofemoral artery bifurcation grafts were placed in 16 patients and unilateral polytetrafluoroethylene femoropopliteal grafts were placed in 10 patients. Half the patients in each group received platelet inhibitors before operation (dipyridamole, 100 mg 4 times a day) and after operation (dipyridamole, 75 mg, and acetylsalicylic acid, 325 mg 3 times a day); the rest of the patients served as control subjects. Five-minute scintigrams of the graft region were taken with a gamma camera interfaced with a computer 48, 72, and 96 hours after injection of the labeled platelets. Platelet deposition was estimated from the radioactivities of the grafts and expressed as counts per 100 pixels per microcurie injected. Dipyridamole and aspirin therapy significantly reduced the number of platelets deposited on Dacron grafts and prevented platelet accumulation over 3 days. With the small amount of platelet deposition on polytetrafluoroethylene femoropopliteal artery grafts even in control patients, platelet inhibitor therapy had no demonstrable effect on platelet deposition on these grafts. It is concluded that (1) platelet deposition on vascular grafts in vivo can be quantitated by noninvasive methods, and (2) dipyridamole and aspirin therapy reduced platelet deposition on Dacron aortofemoral artery grafts

  1. Indium-111 labelled platelet scintigraphy can predict the immunological origin of fever in patients on dialysis carrying a non-functioning renal allograft

    International Nuclear Information System (INIS)

    Fuster, D.; Lomena, F.; Piera, C.; Setoain, F.J.; Laterza, C.; Herranz, R.; Setoain, J.; Torregrosa, J.V.; Oppenheimer, F.

    2000-01-01

    The purpose of this study was to evaluate the usefulness of labelled platelet scintigraphy in the differential diagnosis of a prolonged febrile syndrome (PFS) in patients on dialysis carrying a non-functioning renal allograft. We prospectively performed an indium-111 mercaptopyridine-labelled platelet scan on 91 patients (54 men, 37 women; mean age 39.6±12 years). The mean duration of PFS was 35 days (range 7-122). Forty-six of the 91 patients underwent steroid therapy (2- 10 mg/day). Platelet labelling was carried out following Thakur's method. Platelet scans were performed 48 h after reinjection of labelled platelets. The platelet uptake index (PUI) was calculated by dividing the cpm/pixel in the allograft ROI by cpm/pixel in a mirror background ROI. The final diagnosis of PFS was established depending on the outcome after treatment. In 61/91 patients the fever had an immunological origin because it disappeared after graft embolisation or transplantectomy. In 30/91 patients the PFS disappeared after antibiotic therapy (non-immunological origin). The PUI in patients with immunological PFS was 1.80±0.7, while in patients with non-immunological PFS it was 1.12±0.1 (P 111 In-labelled platelet scintigraphy can accurately predict an immunological PFS in patients on dialysis carrying a non-functioning renal allograft. Therapy with steroids could reduce the sensitivity of 111 In-labelled platelet scintigraphy in detecting immunological PFS. (orig.)

  2. Monoclonal antibody hapten radiopharmaceutical delivery

    International Nuclear Information System (INIS)

    Goodwin, D.A.; McTigue, M.

    1986-01-01

    One hundred μg of monoclonal antibody (MoAb) CHA255 with a binding constant Kb of 4 x 10 9 was complexed with indium-111 labelled BLEDTA II, BLEDTA IV, benzyl EDTA, and an EDTA conjugate of Fab. The 24-h tumour and organ distribution of BALB/c mice bearing KHJJ tumours was studied for each compound alone, the antibody complex, and 3 h following a chelate chase of the antibody complex. Whole body biological half-life was measured for 7 days with and without a chelate chase for each antibody complex. The 24-h whole body counts dropped 20 to 60% and blood concentration fell over 89% within 3 h of administering the chelate chase. Theoretical equivalent human organ doses were calculated from the 24-h organ concentrations, effective half-life, and MIRD 11 S values (absorbed dose per cumulated activity). Liver and spleen were the target organs, with the dose ranging from 0.50 to 3.91 rads mCi -1 . The reduction in organ radiation dose varied up to 95% following the chelate chase. Rapid selective renal clearance of chelate labelled radiopharmaceuticals by competitive inhibition (chelate chase) of their reversible binding to monoclonal antibodies enhances tumour imaging and improves the radiation dosimetry. (author)

  3. Characterization of a tubular flow chamber for studying platelet interaction with biologic and prosthetic materials: deposition of indium 111-labeled platelets on collagen, subendothelium, and expanded polytetrafluoroethylene

    International Nuclear Information System (INIS)

    Badimon, L.; Turitto, V.; Rosemark, J.A.; Badimon, J.J.; Fuster, V.

    1987-01-01

    A plastic (Plexiglas) chamber for evaluating platelet deposition under controlled hemodynamic conditions has been developed. The perfusion chamber has been designed to retain the cylindrical shape typical of the vasculature, to be flexible enough to accept a variety of biologic and prosthetic materials, and to simulate a broad range of physiologic flow conditions in either an ex vivo or in vitro perfusion system. Three type of surfaces were exposed to blood flowing directly from the carotid artery of a heparinized pig through the perfusion chamber: de-endothelialized pig aorta, collagen strips from rabbit Achilles tendon, and an expanded polytetrafluoroethylene material (Gore-Tex). Platelets, previously radiolabeled with indium 111 and injected into the animal, were quantified on the material surface, and the total number of deposited platelets determined for a range of blood flow rates (5 to 40 ml/min) and exposure times (0.5 to 20 minutes). The deposition rates were correlated with theory for describing the mass transport of platelets to the test surface. At the wall shear rates investigated (105 to 850 sec-1), the deposition of platelets on subendothelium was strongly dependent on the local flow conditions. Values of deposition on Gore-Tex obtained at similar flow conditions (105 to 425 sec-1) were reduced compared with that observed on subendothelium and showed a markedly weaker dependence on the shear rate. In contrast, deposition of platelets on collagen was more than an order of magnitude greater than on subendothelium and showed a dependence on flow only at the lowest flow rate studied (10 ml/min). The results indicate that collagen is much more reactive than subendothelium and Gore-Tex with respect to the growth and stability of platelet aggregates and moreover suggest that flow mechanisms for depositing platelets on various surface may be substantially different

  4. Characterization of a tubular flow chamber for studying platelet interaction with biologic and prosthetic materials: deposition of indium 111-labeled platelets on collagen, subendothelium, and expanded polytetrafluoroethylene

    Energy Technology Data Exchange (ETDEWEB)

    Badimon, L.; Turitto, V.; Rosemark, J.A.; Badimon, J.J.; Fuster, V.

    1987-12-01

    A plastic (Plexiglas) chamber for evaluating platelet deposition under controlled hemodynamic conditions has been developed. The perfusion chamber has been designed to retain the cylindrical shape typical of the vasculature, to be flexible enough to accept a variety of biologic and prosthetic materials, and to simulate a broad range of physiologic flow conditions in either an ex vivo or in vitro perfusion system. Three type of surfaces were exposed to blood flowing directly from the carotid artery of a heparinized pig through the perfusion chamber: de-endothelialized pig aorta, collagen strips from rabbit Achilles tendon, and an expanded polytetrafluoroethylene material (Gore-Tex). Platelets, previously radiolabeled with indium 111 and injected into the animal, were quantified on the material surface, and the total number of deposited platelets determined for a range of blood flow rates (5 to 40 ml/min) and exposure times (0.5 to 20 minutes). The deposition rates were correlated with theory for describing the mass transport of platelets to the test surface. At the wall shear rates investigated (105 to 850 sec-1), the deposition of platelets on subendothelium was strongly dependent on the local flow conditions. Values of deposition on Gore-Tex obtained at similar flow conditions (105 to 425 sec-1) were reduced compared with that observed on subendothelium and showed a markedly weaker dependence on the shear rate. In contrast, deposition of platelets on collagen was more than an order of magnitude greater than on subendothelium and showed a dependence on flow only at the lowest flow rate studied (10 ml/min). The results indicate that collagen is much more reactive than subendothelium and Gore-Tex with respect to the growth and stability of platelet aggregates and moreover suggest that flow mechanisms for depositing platelets on various surface may be substantially different.

  5. Effect of different aspirin doses on arterial thrombosis after canine carotid endarterectomy: a scanning electron microscope and indium-111-labeled platelet study

    International Nuclear Information System (INIS)

    Ercius, M.S.; Chandler, W.F.; Ford, J.W.; Swanson, D.P.; Burke, J.C.

    1984-01-01

    Although it is widely accepted that aspirin inhibits platelet aggregation in arterial thrombosis, the appropriate dosage of aspirin remains quite controversial. The purpose of this study was to determine the effect of different doses of aspirin (0.5 mg/kg vs. 10 mg/kg) on mural thrombus formation after carotid endarterectomy. Eighteen hours after oral aspirin administration, 20 endarterectomies were performed on mongrel dogs with the use of the operating microscope. Blood flow was then restored for 3 hours and the vessels were prepared for investigation with the scanning electron microscope. Ten endarterectomies were also performed on unmedicated dogs as controls. Five minutes before vessel unclamping, autologous indium-111-labeled platelets were administered intravenously, and the endarterectomized portions of the vessels were studied with a gamma counter system after harvesting. Group 1, the control group, revealed extensive mural thrombus consisting of platelet aggregates, fibrin, red blood cells, and white blood cells. Six of the 10 vessels in Group 2, premedicated with 0.5 mg of aspirin per kg, demonstrated varying amounts of mural thrombus. Group 3 (10 vessels), premedicated with 10 mg of aspirin per kg, revealed a platelet monolayer completely covering the exposed vessel wall media, with scattered white blood cells and infrequent fine fibrin strands overlying the platelet surface. The mean (+/- SD) radioactivity per group expressed as counts/minute/mm2 was: Group 1--2055.3 +/- 1905.5, log . 7.253 +/- 0.926; Group 2--1235.6 +/- 1234.3, log . 6.785 +/- 0.817; Group 3--526 +/- 433.06, log . 5.989 +/- 0.774

  6. In vitro isotopic determination of diffusion volumes by transferrin labelled with indium 111. study of the correlation with SARI 125; Determination isotopique in vitro de volumes de diffusion par la transferrine marquee a l'indium 111. Etude de la correlation avec la SARI 125

    Energy Technology Data Exchange (ETDEWEB)

    Porot, C.L. [CHU Jean-Minjoz, Service de medecine nucleaire, 25 - Besancon (France); Angoue, O.R. [CHU Jean-Minjoz, laboratoire de biophysique et statistiques, 25 - Besancon (France); Berthetc, L.O. [CHU Jean-Minjoz, 25 - Besancon (France); Ungureanu, C.O.; Boulahdour, H.A.

    2010-07-01

    Serum albumin labeled with iodine 125 (S.A.R.I. 125) is the reference tracer used in measuring isotopic plasma volume. It has been causing a suspension of manufacturing leading to a supply disruption and resulting in the search for an alternative to measure plasma volume under consideration for measuring blood volume. Plasma transferrin labeled with indium-111 (Tf-{sup 111}In) is a potentially useful marker. To this end, we assessed the level of activity to be administered to determine a volume of distribution. The study of the correlation between the volume of distribution values obtained with S.A.R.I. 125 and Tf-{sup 111}In was then performed. Tf is an autologous protein which the labelling is easy and stable. Tf-{sup 111}In is a valid alternative to the S.A.R.I. 125 for measuring the plasma volume. The activity required for this examination shall not exceed 100 micro curies. (N.C.)

  7. Indium 111 DTPA in cisternography

    International Nuclear Information System (INIS)

    Moretti, J.L.; Boumati, P.; Vilayleck, S.

    The circulation of the cerebrospinal fluid was studied in 11 patients following injection of 111 In DTPA. Because of its biological, radioactive and chemical characteristics, it is an ideal radiopharmaceutical [fr

  8. Prediction of infarct volume in patients undergoing reperfusion therapy by Tc-99m antimyosin SPECT

    International Nuclear Information System (INIS)

    Yasuda, T.; Leinbach, R.C.; Khaw, B.A.; Gold, H.K.; Strauss, H.W.

    1984-01-01

    The predictability of infarct volume by Tc-99m antimyosin SPECT was evaluated within 24 hours of chest pain and this was compared to the length of akinesis (AK) from the pre-discharge left ventriculogram (LVgram). Ten patients (pts) with acute myocardial infarction who underwent streptokinase thrombolytic therapy (success 8, failure 2) were subjects of this investigation. None had previous infarction. Average reperfusion time was within 4.5 hours and 20mCi of Tc-99m antimyosin was given intravenously within 8 hours after chest pain; SPECT imaging was performed within 18 hours after injection. Infarct volume was calculated from SPECT and expressed as grams of myocardial infarction (GMI). Ten days later, a 30 0 RAO contrast LVgram was recorded and the length of AK (corrected for magnification) was measured along the LV border at the end-diastolic phase and expressed as cm of AK. GMI and AK were measured independently without knowledge of each other. Results are given. The data demonstrate a good correlation of GMI and AK. Infarct volume can be measured by antimyosin SPECT within 24 hours of chest pain and predict residual LV dysfunction in pts undergoing reperfusion therapy

  9. Study of biodistribution of lipidic nanospheres charged with cis-diaminedichloroplatinum (II) and labelled with radioactive nuclei of Indium-111; Estudio de biodistribucion de nanoesferas lipidicas cargadas con cis-diaminodicloroplatino (II) y marcadas con nucleos radioactivos de Indio-111

    Energy Technology Data Exchange (ETDEWEB)

    Lopez R, V.; Juarez O, C.; Medina L, A. [Unidad de Investigacion Biomedica en Cancer INCAN-UNAM, Mexico D.F. (Mexico); Perez C, E.; Garcia L, P. [Instituto nacional de cancerologia, Mexico D.F. (Mexico)

    2007-07-01

    The general objective of the study was to evaluate the lipidic nanospheres biodistribution charged with cis-diaminedichloroplatinum (II) (cis-DDP) and labelled with radioactive nuclei of Indium-111 (Lip-Cis-in-111) in Wistar rats and in a tumoral model of CaCu. The conclusions were: 1. The system Lip-Cis-in-111 it presents a very fast elimination probably, to a fast recognition response of the reticuloendothelial system (RES). 2. It is planned to make modifications to the formulation to increase the quantity of the hydrophilic polymer (PEG), so that its time of residence in the blood is bigger and allow a bigger accumulation in the tumor. (Author)

  10. Fragmentation, labeling and biodistribution studies of KS1/4, a monoclonal antibody

    International Nuclear Information System (INIS)

    Mohd, S.B.

    1987-01-01

    In this study, an IgG2a (KS1/4), a monoclonal antibody (MoAb) specific against a human lung adenocarcinoma (UCLA P-3) was successfully fragmented enzymatically to yield F(ab') 2 and Fab by using pepsin and papain, respectively. The kinetic of fragmentation of the MoAb was compared to that of human immunoglobulin G (IgG). A similar pattern of fragmentation was observed with both antibodies with a higher percentage yield of the F(ab') 2 and Fab obtained upon the fragmentation of the IgG by the enzymes. The KS1/4 and the two fragments were labeled with three different radionuclides, namely iodine-131, indium-111 and selenium-75. The radioiodination of the MoAb and the fragments was carried out by using a modified chloramine-T method. Radiometal labeling of the MoAb and the fragments with indium-111 was performed by using DTPA as a bifunctional chelating agent, while intrinsic labeling of the MoAb was done by culturing the hybridoma in the presence of 75 Se-methionine. The biodistribution of the radiolabeled MoAb, F(ab') 2 and Fab fragments were performed by injecting the preparations intravenously into nude mice bearing human lung adenocarcinoma

  11. Improved tumor imaging with radiolabeled monoclonal antibodies by plasma clearance with anti-antibody column

    International Nuclear Information System (INIS)

    Lear, J.L.; Kasliwal, R.; Feyerabend, A.; Bunn, P.; Dienhart, D.G.; Johnson, T.K.; Glenn, S.D.; Maddock, S.W.

    1990-01-01

    This paper reports on imaging of tumors with use of radiolabeled monoclonal antibodies (MoAs) that often hindered by high levels of background activity. The ability to lower blood pool MoA activity at a selected time after injection offers a potential method to reduce background while preserving tumor uptake. Toward this goal, the authors investigated the process of clearing MoA from patients' plasma with use of an anti-antibody column. One patient with breast cancer and four with lung cancer were given intravenous injection of 5 mCi of indium-111 KC4 (Coulter Immunology) and imaged at 20, 24, 48, and 72 hours with use of a whole-body canner coupled to a computer. Plasma clearance was performed between the 20- and 24-hour images with use of a COBEIA system. Images were inspected visually and analyzed by region-of-interest quantification

  12. Indium-111 pentetreotide single-photon emission tomography in patients with TSH-secreting pituitary adenomas: correlation with the effect of a single administration of octreotide on serum TSH levels

    Energy Technology Data Exchange (ETDEWEB)

    Losa, M. [Department of Neurosurgery, IRCCS San Raffaele, University of Milan (Italy); Magnani, P. [INB-CNR Department of Nuclear Medicine, IRCCS San Raffaele, University of Milan (Italy); Mortini, P. [Department of Neurosurgery, IRCCS San Raffaele, University of Milan (Italy); Persani, L. [Centro Auxologico Italiano IRCCS, University of Milan (Italy); Acerno, S. [Department of Neurosurgery, IRCCS San Raffaele, University of Milan (Italy); Giugni, E. [Department of Neurosurgery, IRCCS San Raffaele, University of Milan (Italy); Songini, C. [INB-CNR Department of Nuclear Medicine, IRCCS San Raffaele, University of Milan (Italy); Fazio, F. [INB-CNR Department of Nuclear Medicine, IRCCS San Raffaele, University of Milan (Italy); Beck-Peccoz, P. [Institute of Endocrine Sciences, Istituto Clinico Humanitas, University of Milan (Italy); Giovanelli, M. [Department of Neurosurgery, IRCCS San Raffaele, University of Milan (Italy)

    1997-07-01

    Few data are available on the visualization of somatostatin receptors in vivo in patients with thyrotropin (TSH)-secreting adenoma. We studied five patients with TSH-secreting adenomas using single-photon emission tomography (SPET) after administration of indium-111 pentetreotide. The intensity of {sup 111}In-pentetreotide uptake by the tumours was correlated with the degree of TSH suppression after a single administration of 100 {mu}g octreotide s.c. Five patients (three women and two men) aged 27-46 years were investigated. Except for one patient with acromegaly, all had pure TSH-secreting tumours. One patient was previously untreated, while two had received octreotide, one antithyroid drugs, and one radioiodine. In all patients SPET demonstrated increased uptake of {sup 111}In-pentetreotide by the pituitary adenoma. The target to non-target ratio (T/nT) of {sup 111}In-pentetreotide uptake was higher than 10 in three patients. Administration of 100 {mu}g octreotide s.c. caused a significant reduction in TSH levels from 4.8{+-}1.4 mU/l to a nadir of 3.1{+-}1.1 mU/l after 6 h (P<0.001 by ANOVA). Suppression of TSH secretion ranged from 30% to 60% of the baseline value. The T/nT ratio showed a trend toward a direct relationship with the degree of TSH inhibition after acute octreotide administration (r=0.67; P=NS). Our study showed that {sup 111}In-pentetreotide scan visualized somatostatin receptors in all five of the patients with TSH-secreting pituitary adenomas, confirming the frequent presence of somatostatin receptors in these rare tumours, even though the correlation with the TSH inhibition after a single administration of octreotide did not reach significance. (orig.). With 1 fig., 1 tab.

  13. Scintigraphic detection of inflammatory heart disease

    International Nuclear Information System (INIS)

    Morguet, A.J.; Munz, D.L.; Kreuzer, H.; Emrich, D.

    1994-01-01

    Inflammatory diseases of the heart encompass myocarditis, endocarditis and pericarditis. This paper discusses the diagnostic potential of scintigraphy in these entities. In myocarditis, indium-111 antimyosin Fab imaging can visualize active myocyte damage and thus contribute substantially to the diagnosis. Antimyosin uptake is also seen in a large subset of patients with dilated cardiomyopathy, indicating ongoing myocyte injury in these cases. In endocarditis, immunoscintigraphy using monoclonal technetium-99m-labelled antigranulocyte antibodies provides useful diagnostic information in patients with equivocal echocardiographic findings. Immunoscintigraphy seems to indicate the floridity of the inflammatory process in endocarditis and may be used to monitor antibiotic therapy. In pericarditis, the clinical value of scintigraphy has not been convincingly demonstrated. (orig.)

  14. Scintigraphic detection of inflammatory heart disease

    Energy Technology Data Exchange (ETDEWEB)

    Morguet, A J [Dept. of Cardiology and Pulmonology, Centre of Internal Medicine, Georg August Univ., Goettingen (Germany); Munz, D L [Dept. of Nuclear Medicine, Centre of Radiology, Georg August Univ., Goettingen (Germany); Kreuzer, H [Dept. of Cardiology and Pulmonology, Centre of Internal Medicine, Georg August Univ., Goettingen (Germany); Emrich, D [Dept. of Nuclear Medicine, Centre of Radiology, Georg August Univ., Goettingen (Germany)

    1994-07-01

    Inflammatory diseases of the heart encompass myocarditis, endocarditis and pericarditis. This paper discusses the diagnostic potential of scintigraphy in these entities. In myocarditis, indium-111 antimyosin Fab imaging can visualize active myocyte damage and thus contribute substantially to the diagnosis. Antimyosin uptake is also seen in a large subset of patients with dilated cardiomyopathy, indicating ongoing myocyte injury in these cases. In endocarditis, immunoscintigraphy using monoclonal technetium-99m-labelled antigranulocyte antibodies provides useful diagnostic information in patients with equivocal echocardiographic findings. Immunoscintigraphy seems to indicate the floridity of the inflammatory process in endocarditis and may be used to monitor antibiotic therapy. In pericarditis, the clinical value of scintigraphy has not been convincingly demonstrated. (orig.)

  15. Comparision of indium-111 oxinate labelled autologous granulocytes with indium-111 oxinate and indium-111 chloride as abscess scanning agents

    International Nuclear Information System (INIS)

    Goedemans, W.T.; Hardemann, M.R.; Belfer, A.J.

    1980-01-01

    Bacterial abscesses were evoked in goats. Imaging of these abscesses was obtained by means of labelling autologous granulocytes with 111 In oxinate, reinjection of the cells into the animal, and scintigraphy by gamma camera one day later. Comparable imaging results, however, were obtained after intravenous of 111 In oxinate or of 111 In chloride. The gamma camera images were supported by tissue distribution studies. In the case of administration of 111 In oxinate to the goats, the radioactivity accumulated in the cell fraction of the blood to a significant extent. This did not occur in the case of plain 111 In chloride. It remained unexplained why such different accumulation in cells did not result in differences in the scintigraphic studies. Blood clearance studies supplied conclusive evidence that the granulocytes stayed in the circulation for several days following labelling with 111 In oxinate and reinjection of the cells into the animals. (orig.) [de

  16. Leukemic cell labeling with indium-111-oxine

    International Nuclear Information System (INIS)

    Uchida, T.; Takagi, Y.; Matsuda, S.; Yui, T.; Ishibashi, T.; Kimura, H.; Kariyone, S.

    1984-01-01

    Leukemic cells were labeled with In-111-oxine in patients with acute leukemia. In vitro labeling studies revealed that labeling efficiency reached maximum 80.8 +- 3.6% (mean +- 1SD) by 2 times washes after 20 minutes incubation time. Cell viability was assessed by trypan blue exclusion test and in vitro culture of leukemic cells, which showed no cellular damage during labeling procedure. Elution of In-111 from the labeled cells was 10.0 +- 1.2% at 12 hours after labeling. For in vivo leukemic cell kinetic studies, more than 10/sup 8/ leukemic cells separated from Ficoll-Hypacque sedimentation were labeled by 30 minutes of In-111-oxine incubation and two times washes at 37 0 C. In vivo studies were performed in 7 patients with acute myeloblastic, lymphoblastic leukemia and blastic crisis of chronic myelocytic leukemia. Labeled leukemic cells disappeared in single exponential fashion with half life of 9.6 to 31.8 hours. Total leukemic cell pool in peripheral circulation was calculated, which correlated well with peripheral leukemic cell counts (r=0.99). No relationship was observed between total leukemic cell pool and leukemic cell turnover rate. Migration patterns of labeled leukemic cells showed that pulmonary uptake was evident within 15 minutes after the infusion and returned to base-line. Splenic and hepatic uptake showed gradual increase up to 24 hours. Bone marrow accumulation was shown only in 2 cases. Presently, there are no suitable radionuclides for leukemic cell labeling. In-111-oxine labeled leukemic cells would overcome this difficulty

  17. Imaging thrombus with radiolabelled monoclonal antibody to platelets

    International Nuclear Information System (INIS)

    Loutfi, I.; Peters, A.M.; Lavender, J.P.; Epenetos, A.A.

    1988-01-01

    Indium-111-hydroxyquinoline labelled platelets, though useful in the detection of thrombus, have not gained widespread use owing to the time and technical skill required for their preparation. A study was therefore conducted evaluating a new method of imaging thrombus with platelets radiolabelled with a 111 In labelled monoclonal antibody, P 256 , directed to the platelet surface glycoprotein complex IIb/IIIa. When the number of receptors occupied by P 256 was less than 3% of the total available on the platelet surface platelet function, as assessed by platelet aggregometry, was undisturbed. P 256 was radiolabelled with 111 In using diethylenetriaminepenta-acetic acid, which achieved a specific activity of 185 MBq (5 mCi)/mg. No impairment of immunoreactivity was detected at this specific activity. Platelets were labelled with radiolabelled monoclonal antibody in vitro in two patients at a receptor occupancy of 6% and in vivo - that is, by direct intravenous injection of P 256 - in six patients at a receptor occupancy of 1%. In vivo recovery and biodistribution kinetics suggested that after in vitro labelling platelets were minimally activated. The 111 In kinetics recorded after intravenous P 256 suggested rapid and efficient radiolabelling of platelets and gave no indication of platelet activation. Of the six patients who received intravenous P 256 , three had documented thrombus, tow of whom gave positive results on P 256 platelet scintigraphy. The third subject had chromic deep venous thrombosis and was scintigraphically negative. Imaging thrombus using a radiolabelled monoclonal antibody directed to platelets appears to offer great potential as a simple, non-invasive approach to the diagnosis of thrombosis. 3 refs. (Author)

  18. Monoclonal antibody

    International Nuclear Information System (INIS)

    Oyamada, Hiyoshimaru

    1987-01-01

    Some aspects of monoclonal antibodies are described, centering on studies made by the author and those presented at the Second International Conference on Monoclonal Antibody Immunoconjugates for Cancer held in March this year (1987). The history of immuno-nuclear medicine and procedures for producing monoclonal antibodies are briefly outlined. Monoclonal antibodies are immunoglobulins. Here, the structure of IgG, which is used most frequently, is described. An IgG is composed of two antigen binding fragments (Fab) and one crystallizable fragment (Fc). The end portion of a Fab reacts with an antigen. One of the major applications of immuno-nuclear medicine is the diagnosis of cancer. As label nucleides, 131 I and 111 I were selected in most cases in the past while 123 I and 99m Tc are currently used more often. Advantages and disadvantages of this diagnosis method is discussed citing studies presented at the First (1986) and Second (1987) International Conference on Monoclonal Antibody Immunoconjugates for Cancer. The present status of the application of monoclonal antibodies to treatment of cancer is also described. (Nogami, K.)

  19. Scintigraphy in a case of Churg-Strauss vasculitis with myocardial involvement using 111In-labelled antimyosin

    International Nuclear Information System (INIS)

    Krause, T.; Schuemichen, C.; Beck, A.; Moser, E.; Lang, B.; Hohnloser, S.

    1990-01-01

    A case of Churg-Strauss vasculitis in a young woman is reported. Diagnosis was confirmed by muscle biopsy. Affection of lungs, kidneys and skin was evident. In addition, myocarditis was suspected on clinical evidence. A highly positive scintigraphy with 111 In-antimyosin enabled diagnosis and assessment of damage to the myocytes. With a heart-to-lung ratio of 3.0 the accumulated activity in the myocardium was higher than usually found in myocarditis. This finding supports the hypothesis of an additional ischemic necrosis. (orig.) [de

  20. Relation of immediate and delayed thallium-201 distribution to localization of iodine-125 antimyosin antibody in acute experimental myocardial infarction

    International Nuclear Information System (INIS)

    Khaw, B.A.; Strauss, H.W.; Pohost, G.M.; Fallon, J.T.; Katus, H.A.; Haber, E.

    1983-01-01

    Thallium-201 (TI-201) distribution in acute experimental myocardial infarction (MI) (n . 18) was compared with cardiac-specific antimyosin Fab (AM-Fab) uptake, a specific marker for myocardial necrosis. When antimyosin was injected 4 hours after ligation with TI-201 administered 23 hours 55 minutes later and measurement of myocardial distribution determined 5 minutes after intravenous administration of TI-201, (1) TI-201 distribution closely correlated with microsphere regional blood flow, and (2) an inverse exponential relation to iodine-125 (I-125) AM-Fab uptake was apparent. In another group of 4 animals, TI-201 and AM-Fab were administered intravenously 4 hours after MI, and 36 hours later myocardial distribution was measured. This delayed TI-201 distribution had a close inverse linear correlation with I-125 AM-Fab uptake. This inverse linear relation also was apparent in 28-hour-old MIs in dogs (n . 4) where collateral circulation had been established. TI-201 was administered intravenously at 27 hours after MI, and TI-201 distribution was determined 1 hour later. The present study demonstrated that whereas immediate TI-201 distribution is flow-limited, delayed TI-201 distribution is a marker of cell viability which, due to prolonged circulation time and redistribution, is not flow-limited

  1. Chelate chase of radiopharmaceuticals reversibly bound to monoclonal antibodies improves dosimetry

    International Nuclear Information System (INIS)

    Goodwin, D.A.; Smith, S.I.; Meares, C.F.; David, G.S.; McTigue, M.; Finston, R.A.

    1986-01-01

    One hundred micrograms of monoclonal antibody (MoAb) CHA 255 with a binding constant Kb of 4 x 10 9 was complexed with indium-111 labeled BLEDTA II, GLEDTA IV, benzyl EDTA, and an EDTA conjugate of Fab. The 24-hour tumor and organ distribution in BALB/c mice bearing KHJJ tumors was studied for each compound alone, the antibody complex, and 3 hours following a chelate chase of the antibody complex. Whole-body biological half-life was measured for 7 days with and without a chelate chase for each antibody complex. The 24-hour whole-body counts dropped 20-60% within 3 hours of administering the chelate chase. Blood concentration fell over 89% within 3 hours of administering the chase and there was a decrease in concentration in all organs, except the kidneys, of 10 to 85%. Theoretical equivalent human doses were calculated from the 24-hour organ concentrations, effective half-life, and MIRD 11 S values (absorbed dose per cumulated activity). Liver and spleen were the target organs, with the dose ranging from 0.50 to 3.91 rads per millicurie. The reduction in organ radiation dose varied up to 95% following the chelate chase. Rapid selective renal clearance of chelate labeled radiopharmaceuticals by competitive inhibition (chelate chase) of their reversible binding to monoclonal antibodies, greatly improves the radiation dosimetry of tumor imaging agents. 28 references, 5 figures, 5 tables

  2. Evaluation of a technique for the intraoperative detection of a radiolabelled monoclonal antibody against colorectal cancer

    International Nuclear Information System (INIS)

    Waddington, W.A.; Todd-Pokropek, A.; Short, M.D.; Davidson, B.R.; Boulos, P.B.; Middlesex Hospital, London

    1991-01-01

    Occult tumour deposits may be localised at operation with a radiation detecting probe following the administration of a radiolabelled monoclonal antibody (MoAb) recognising a tumour-associated antigen. We have recently evaluated the clinical usefulness of this technique in detecting primary colorectal tumours targetted with an indium-111 MoAb. In the present study the physical characteristics of the two detector systems used were investigated; a sodium iodide [NaI(Tl)] scintilation detector and a cadmium telluride (CdTe) semiconductor probe. Limitations of the technique in use have been examined by testing the statistical significance of tumour detecting using an abdominal phantom based on the currently available clinical biodistribution data for tumour uptake of radiolabelled MoAbs. The effect of tumour volume, antibody uptake, collimation and counting conditions was examined. Results indicate that tumours of 10-ml volume may be detected with the NaI(Tl) probe at the lowest levels of radiolabelled antibody uptake currently reported in the literature but that at higher published levels, lesions as small as 1 ml may be identified with both detector systems. Detector sensitivity and limited antibody specificity restrict the usefulness of the technique, although moderate improvements in tumour uptake may allow the detection of tumour deposits not clinically apparent. The statistical significance criterion used for this study could be an accurate and reliable indicator for tumour detection in vivo. (orig.)

  3. The radiolabeled monoclonal antibodies in immunoscintigraphy and radioimmunotherapy: current state and perspectives

    International Nuclear Information System (INIS)

    Chatal, J. F.

    2000-01-01

    The antibodies can be satisfactorily labelled with technitium-99 m or indium-111 for tumor immunoscintigraphy. The immunoscintigraphy is not useful for the primary tumor diagnosis. It can be useful for the diagnosis of the some cancer extension and for recurrent tumor visualization. The immunoscintigraphy is widely competed with Positron Emission Tomography (PET) which gives accurate results. In the future the immunoscintigraphy, in pre-therapeutic stage, contribute to the estimation of the dose delivered to the tumor and to normal organs for adopting or not a radioimmunotherapy. The antibodies can also be labeled with Iodine-131 for an application in radioimmunotherapy (RIT). The RIT is efficient in the non-Hodgkin's lymphoma treatment because of their great radiosensitivity. Until now the results have been very modest in solid tumor treatment but methodological and biotechnological progresses have to improve the efficiency especially for the small tumors. In the future iodine-131 which requires the confinement (very expensive) of patients will be substituted by yttrium-90 beta emitter, more energetic than iodine-131 and can be injected in walking case. In the long term, the alpha emitter radionuclides (astatine-211 or bismuth-213) can be used for hematologic cancer treatment. In conclusion the future of radiolabeled monoclonal antibodies is essentially therapeutic. The radioimmunotherapy associated to the chemotherapy give promising perspectives for the radiosensitive cancer treatment and in general small solid tumor treatment (F.M.)

  4. Colorectal carcinoma metastases: Detection with In-111-labeled monoclonal antibody CCR 086

    International Nuclear Information System (INIS)

    Abdel-Nabi, H.H.; Levine, G.; Lamki, L.M.; Murray, J.L.; Tauxe, W.N.; Shah, A.N.; Patt, Y.Z.; Doerr, R.J.; Klein, H.A.; Gona, J.

    1990-01-01

    A phase I/II clinical trial with indium-111-labeled antimucin murine monoclonal antibody (MoAb) CCR 086 was conducted. Seventeen patients with histologically proved colorectal carcinoma and known metastatic disease underwent external scintigraphy after administration of 5.5 mCi (203.5 MBq) of In-111 CCR 086 at doses of 5 and 20 mg. Of 25 known lesions, 17 were detected (sensitivity, 68%). The smallest detected lesion in the lung was 1 cm and in the liver was 1.5 cm. The serum half-life of In-111-labeled CCR 086 MoAb was approximately 64 hours. The formation of human antimouse antibody (HAMA) was detected in the serum of four of five patients who received 20 mg of MoAb. No HAMAs were detected in four patients receiving 5 mg of MoAb. No side effects were encountered. Because of effective detection of liver and lung metastases with lower doses (5-20 mg) of CCR 086 conjugated with In-111, further investigations are warranted to assess clinical and therapeutic potentials of CCR 086 in the management of colorectal cancer

  5. Synthesis of novel bifunctional chelators and their use in preparing monoclonal antibody conjugates for tumor targeting

    International Nuclear Information System (INIS)

    Westerberg, D.A.; Carney, P.L.; Rogers, P.E.; Kline, S.J.; Johnson, D.K.

    1989-01-01

    Bifunctional derivatives of the chelating agents ethylenediaminetetraacetic acid and diethylenetriaminepentaacetic acid, in which a p-isothiocyanatobenzyl moiety is attached at the methylene carbon atom of one carboxymethyl arm, was synthesized by reductive alkylation of the relevant polyamine with (p-nitrophenyl)pyruvic acid followed by carboxymethylation, reduction of the nitro group, and reaction with thiophosgene. The resulting isothiocyanate derivatives reacted with monoclonal antibody B72.3 to give antibody-chelator conjugates containing 3 mol of chelator per mole of immunoglobulin, without significant loss of immunological activity. Such conjugates, labeled with the radioisotopic metal indium-111, selectively bound a human colorectal carcinoma implanted in nude mice when given intravenously. Uptake into normal tissues was comparable to or lower than that reported for analogous conjugates with known bifunctional chelators. It is concluded that substitution with a protein reactive group at this position in polyaminopolycarboxylate chelators does not alter the chelating properties of these molecules to a sufficient extent to adversely affect biodistribution and thus provides a general method for the synthesis of such chelators

  6. Qualification of viable myocardium in the infarcted area by dual isotope In-111 antimyosin Fab and thallium SPECT imaging

    International Nuclear Information System (INIS)

    Mitani, Isao; Nishimura, Tsunehiko; Uehara, Toshiisa; Hayashida, Kouhei; Kumita, Shin-ichirou; Oka, Hisatsugu; Haze, Kazuo; Nonoki, Hiroshi

    1991-01-01

    Dual isotope In-111 antimyosin (AM) Fab and thallium SPECT imaging was performed in 33 patients with acute myocardial infarction. Thirteen patients in whom coronary reperfusion could successfully be achieved at the acute stage had higher AM uptake parameters, including AM SCORE, AM AREA, and SCORE/AREA, and the maximum CPK value than the other 20 patients. Left ventricular ejection fraction had a stronger correlation with AM AREA than with AM SCORE (0.601 vs 0.387). Overlap phenomenon was seen in 18 patients (55%). In 28 patients followed up with coronary arteriography, 10 patients had a ≥75% coronary stenosis in the infarct-related vessel; 5 of these 10 had ischemic events. In 13 patients undergoing subsequent thallium-201 scintigraphy at rest, 6 (46%) were found to have marked reduction of perfusion defect (the improved group). Regarding thallium-201 DEFECT SCORE early after the onset of myocardial infarction, there was no significant difference between the aforementioned improved group (15±5) and the non-improved group (17±7). However, In-111 AM uptake in the infarct area was smaller in the improved group than the non-improved group, which means that the infarcted area did not become necrotic early after the onset of myocardial infarction. This may have been responsible for the improvement of perfusion defect in cases of myocardial infarction. (N.K.)

  7. Current status of cancer immunodetection with radiolabeled human monoclonal antibodies.

    Science.gov (United States)

    De Jager, R; Abdel-Nabi, H; Serafini, A; Pecking, A; Klein, J L; Hanna, M G

    1993-04-01

    The use of radiolabeled murine monoclonal antibodies (MoAbs) for cancer immunodetection has been limited by the development of human antimouse antibodies (HAMA). Human monoclonal antibodies do not elicit a significant human antihuman (HAHA) response. The generation and production of human monoclonal antibodies met with technical difficulties that resulted in delaying their clinical testing. Human monoclonal antibodies of all isotypes have been obtained. Most were immunoglobulin (Ig) M directed against intracellular antigens. Two antibodies, 16.88 (IgM) and 88BV59 (IgG3k), recognize different epitopes on a tumor-associated antigen, CTA 16.88, homologous to cytokeratins 8, 18, and 19. CTA 16.88 is expressed by most epithelial-derived tumors including carcinomas of the colon, pancreas, breast, ovary, and lung. The in vivo targeting by these antibodies is related to their localization in nonnecrotic areas of tumors. Repeated administration of 16.88 over 5 weeks to a cumulative dose of 1,000 mg did not elicit a HAHA response. Two of 53 patients developed a low titer of HAHA 1 to 3 months after a single administration of 88BV59. Planar imaging of colorectal cancer with Iodine-131 (131I)-16.88 was positive in two studies in 9 of 12 and 16 of 20 patients preselected by immunohistochemistry. Tumors less than 2 cm in diameter are usually not detected. The lack of immunogenicity and long tumor residence time (average = 17 days) makes 16.88 a good candidate for therapy. Radioimmunlymphoscintigraphy with indium-111 (111In)-LiLo-16.88 administered by an intramammary route was used in the presurgical staging of primary breast cancer. The negative predictive value of lymph node metastases for tumors less than 3 cm was 90.5%. Planar and single photon emission computed tomography imaging of colorectal carcinoma with technetium-99m (99mTc) 88BV59 was compared with computed tomography (CT) scan in 36 surgical patients. The antibody scan was more sensitive than the CT scan in detecting

  8. Prognosis in monoclonal proteinaemia

    NARCIS (Netherlands)

    Schaar, Cornelis Gerardus

    2006-01-01

    Monoclonal proteinaemia (M-proteinemia) is associated with multiple myeloma (MM) or other hematological malignancies. In the absence of these diseases the term MGUS (Monoclonal Gammopathy of Undetermined Significance) is used. During 1991-1993 1464 patients with newly diagnosed M-proteinemia in the

  9. Therapeutic Recombinant Monoclonal Antibodies

    Science.gov (United States)

    Bakhtiar, Ray

    2012-01-01

    During the last two decades, the rapid growth of biotechnology-derived techniques has led to a myriad of therapeutic recombinant monoclonal antibodies with significant clinical benefits. Recombinant monoclonal antibodies can be obtained from a number of natural sources such as animal cell cultures using recombinant DNA engineering. In contrast to…

  10. Nuclear medicine: Monoclonal antibodies

    International Nuclear Information System (INIS)

    Endo, K.; Sakahara, H.; Koizumi, M.; Kawamura, Y.; Torizuka, K.; Yokoyama, A.

    1986-01-01

    Antitumor monoclonal antibody was successfully labeled with Tc-99m by using dithiosemicarbazone (DTS) as a bifunctional chelating agent. In the first step, DTS was coupled to antibody without loss of immunoreactivity; the compound then efficiently formed a neutral 1:1 chelate with pentavalent or tetravalent Tc-99m. Imaging with Tc-99m-labeled monoclonal antibody to human osteosarcoma (OST-7) clearly displayed a small tumor in nude mice at 6 and 24 hours after intravenous administration. The tumor-to-blood ratio of the Tc-99m-labeled monoclonal antibody was higher than that of a radioiodinated antibody and similar to that of an In-111-labeled antibody. Thus, conjugation of DTS to monoclonal antibody followed by radiometalation is a simple and efficient method of preparing Tc-99m-labeled monoclonal antibody

  11. 99mTc-annexin V and 111In-antimyosin antibody uptake in experimental myocardial infarction in rats

    International Nuclear Information System (INIS)

    Sarda-Mantel, Laure; Rouzet, Francois; Martet, Genevieve; Raguin, Olivier; Vrigneaud, Jean-Marc; Guludec, Dominique Le; Michel, Jean-Baptiste; Louedec, Liliane; Vanderheyden, Jean-Luc; Hervatin, Florence; Khaw, Ban An

    2006-01-01

    99m Tc-annexin V (ANX) allows scintigraphic detection of apoptotic cells via specific binding to exposed phosphatidylserine. In myocardial infarction, apoptosis of myocytes is variable and depends especially on the presence or absence of coronary reperfusion. In this study, ANX uptake in non-reperfused experimental myocardial infarcts was compared with uptake of a marker of myocyte necrosis ( 111 In-antimyosin antibodies, AM) and an immunohistochemical marker of apoptosis (Apostain). The left anterior coronary artery was ligated in 47 Wistar rats, which were then injected with ANX (n=20), AM (n=21) or both (n=6). Myocardial uptake of ANX and AM was determined at 2 h (n=14), 4 h (n=14) and 24 h (n=19) after coronary ligation (CL), by quantitative autoradiography with (n=23) or without (n=24) gamma imaging. Heart-to-lung ratios (HLRs) and infarct-to-remote myocardium activity ratios (INRs) were calculated on the scintigrams and autoradiograms respectively. Cardiac sections were stained with haematoxylin-eosin and Apostain. The above studies were repeated in 12 normal rats. All rats with CL showed increased ANX and AM uptake in cardiac areas on scintigrams 24 h after CL, with HLRs higher than in controls: 3.1±0.6 versus 1.5±0.3 (p=0.001) for ANX and 1.99±0.44 versus 1.01±0.05 (p<0.0005) for AM. Autoradiography showed intense ANX and AM uptake in infarcts, with comparable topography and INRs at 2 h, 4 h and 24 h after CL (4.6±0.9 versus 5.0±1.8 at 24 h), while Apostain staining was very low (0.06±0.06% of cells). In this model of persistent CL, we observed increased ANX uptake in injured myocardium, comparable in intensity, topography and kinetics to that of AM. There was only minimal Apostain staining in the same areas. (orig.)

  12. Quantification of the sequestration of indium 111 labelled platelets

    International Nuclear Information System (INIS)

    Najean, Y.; Picard, N.; Dufour, V.; Rain, J.D.

    1988-01-01

    A simple method is proposed for an accurate quantification of the splenic and/or hepatic sequestration of the 111 In-labelled platelets. It could be allow a better prediction of the efficiency of splenectomy in idiopathic thrombocytopenic purpura [fr

  13. The kinetics of short-lived Indium-111 radiolabelled platelets

    International Nuclear Information System (INIS)

    Peters, A.M.; Saverymuttu, S.H.; Bell, R.N.; Lavender, J.P.

    1985-01-01

    We have studied the kinetics of autologous 111 In-labelled platelets in patients with reduced platelet life span ( 111 In-labelled platelets in patients with severe thrombocytopenia. Intrasplenic platelet transit time (t) was calculated by compartmental and deconvolution analysis. In patients with a mean platelet life span of less than a few h, compartmental analysis may not be valid and so only deconvolution analysis was applied. There was a close correlation between values of t given by the two approaches (r=0.88, n=18, P<0.001). In some patients with severely reduced mean platelet life span (MPLS), the deconvolved splenic platelet clearance curves appeared to approach an asymptote, the relative magnitude of which was indicative of the irreversible extraction fraction by the spleen of incoming platelets. In othe patients with severely reduced MPLS resulting from abnormal intra-hepatic platelet destruction, the deconvolved splenic curves resembled the normal. The intrasplenic platelet transit time showed no clear relationship with other parameters. It was concluded that platelet pooling within the spleen is normal in patients with reduced platelet life span,including idiopathic thrombocytopenic purpura, even when the predominant site of destruction is the spleen, and that platelets are not delayed in transit through the spleen in preparation of their removal from the circulation and ultimate destruction. (author)

  14. Kinetics of short-lived Indium-111 radiolabelled platelets

    Energy Technology Data Exchange (ETDEWEB)

    Peters, A.M.; Saverymuttu, S.H.; Bell, R.N.; Lavender, J.P. (Hammersmith Hospital, London, U.K.)

    1985-01-01

    We have studied the kinetics of autologous /sup 111/In-labelled platelets in patients with reduced platelet life span (<4.5 d), most of whom were thrombocytopenic, and of homologous /sup 111/In-labelled platelets in patients with severe thrombocytopenia. Intrasplenic platelet transit time (t) was calculated by compartmental and deconvolution analysis. In patients with a mean platelet life span of less than a few h, compartmental analysis may not be valid and so only deconvolution analysis was applied. There was a close correlation between values of t given by the two approaches (r=0.88, n=18, P<0.001). In some patients with severely reduced mean platelet life span (MPLS), the deconvolved splenic platelet clearance curves appeared to approach an asymptote, the relative magnitude of which was indicative of the irreversible extraction fraction by the spleen of incoming platelets. In other patients with severely reduced MPLS resulting from abnormal intra-hepatic platelet destruction, the deconvolved splenic curves resembled the normal. The intrasplenic platelet transit time showed no clear relationship with other parameters. It was concluded that platelet pooling within the spleen is normal in patients with reduced platelet life span,including idiopathic thrombocytopenic purpura, even when the predominant site of destruction is the spleen, and that platelets are not delayed in transit through the spleen in preparation of their removal from the circulation and ultimate destruction.

  15. Indium-111 labelled platelets: experimental and clinical studies

    International Nuclear Information System (INIS)

    Gjerloeff Schmidt, K.

    1985-10-01

    The object of the present study became to develop a method of effective and gentle isolation and 111-In labelling of human platelets, as well as to employ these platelets in human clinical studies with the object of elucidating a number of physiological and pathophysiological mechanisms and processes in which platelets take part. 111-In-oxine presents obvious advantages over 51-Cr-sodium chromate; a high labelling efficiency, and more advantageous physical properties (a half life of 68 hours (against the half life of 28 days for 51-Cr) and considerably more effective gamma emission), making external registration by means of a gamma camera possible. Considering the role played by platelets in the development of atherosclerosis and its thromboembolic complications, in the early phases of deep venous thrombosis, and in graft rejection, it is natural that attempts have been made to use 111-In-labelled platelets for scintigraphic and kinetic evaluation of thromboembolic processes. Accumulation of 111-In-labelled platelets at sites of vessel wall injury, on pulmonary emboli (presumably on deep vein thrombi as well), and on catheter material has been demonstrated. Beyond this, the number of publications concerning the use of 111-In-labelled platelets for visualization of atherosclerosis, venous thromboembolism, arterial grafts, intracardiac thrombi, aortic aneurysms, renal allograft rejection, and other situations in which platelet thromboembolism takes place, provides evidence that a tool has finally been found for the study of their nature and response to therapeutic intervention. (eg)

  16. Experience with indium-111 and yttrium-90-labeled somatostatin analogs.

    Science.gov (United States)

    Virgolini, I; Traub, T; Novotny, C; Leimer, M; Füger, B; Li, S R; Patri, P; Pangerl, T; Angelberger, P; Raderer, M; Burggasser, G; Andreae, F; Kurtaran, A; Dudczak, R

    2002-01-01

    The high level expression of somatostatin receptors (SSTR) on various tumor cells has provided the molecular basis for successful use of radiolabeled octreotide / lanreotide analogs as tumor tracers in nuclear medicine. Other (nontumoral) potential indications for SSTR scintigraphy are based on an increased lymphocyte binding at sites of inflammatory or immunologic diseases such as thyroid-associated ophthalmology. The vast majority of human tumors seem to over-express the one or the other of five distinct hSSTR subtype receptors. Whereas neuroendocrine tumors frequently overexpress hSSTR2, intestinal adenocarcinomas seem to overexpress more often hSSTR3 or hSSTR4, or both of these hSSTR. In contrast to In-DTPA-DPhe(1)-octreotide (OctreoScan(R)) which binds to hSSTR2 and 5 with high affinity (Kd 0.1-5 nM), to hSSTR3 with moderate affinity (K(d) 10-100 nM) and does not bind to hSSTR1 and hSSTR4, (111)In / (90)Y-DOTA-lanreotide was found to bind to hSSTR2, 3, 4, and 5 with high affinity, and to hSSTR1 with lower affinity (K(d) 200 nM). Based on its unique hSSTR binding profile, (111)In-DOTA-lanreotide was suggested to be a potential radioligand for tumor diagnosis, and (90)Y-DOTA-lanreotide suitable for receptor-mediated radionuclide therapy. As opposed to (111)In-DTPA-DPhe(1)-octreotide and (111)In-DOTA-DPhe(1)-Tyr(3)-octreotide, discrepancies in the scintigraphic results were seen in about one third of (neuroendocrine) tumor patients concerning both the tumor uptake as well as detection of tumor lesions. On a molecular level, these discrepancies seem to be based on a "higherrdquuo; high-affinity binding of (111)In-DOTA-DPhe(1)-Tyr(3)-octreotide to hSSTR2 (K(d) 0.1-1 nM). Other somatostatin analogs with divergent affinity to the five known hSSTR subtype receptors have also found their way into the clinics, such as (99m)Tc-depreotide (NeoSpect(R); NeoTect(R)). Most of the imaging results are reported for neuroendocrine tumors (octreotide analogs) or nonsmall cell lung cancer ((99m)Tc-depreotide), indicating high diagnostic cabability of this type of receptor tracers. Consequently to their use as receptor imaging agents, hSSTR recognizing radioligands have also been implemented for experimental receptor-targeted radionuclide therapy. Beneficial results were reported for high-dose treatment with (111)In-DTPA-DPhe(1)-octreotide, based on the emission of Auger electrons. The Phase IIa study "MAURITIUS" (Multicenter Analysis of a Universal Receptor Imaging and Treatment Initiative, a eUropean Study) showed in progressive cancer patients (therapy entry criteria) with a calculated tumor dose > 10 Gy / GBq (90)Y-DOTA-lanreotide, the proof-of-principle for treating tumor patients with peptide receptor imaging agents. In the "MAURITIUS" study, cummulative treatment doses up to 200 mCi (90)Y-DOTA-lanreotide were given as short-term infusion. Overall treatment results in 70 patients indicated stable tumor disease in 35% of patients and regressive tumor disease in 10% of tumor patients with different tumor entities expressing hSSTR. No acute or chronic severe hematological toxicity, change in renal or liver function parameters due to (90)Y-DOTA-lanreotide treatment, were reported. (90)Y-DOTA-DPhe(1)-Tyr(3)-octreotide may show a higher tumor uptake in neuroendocrine tumor lesions and may therefore be superior for treatment in patients with neuroendocrine tumors. However, there is only limited excess to long-term and survival data at present. Potential indications for (90Y-DOTA-lanreotide are radioiodine-negative thyroid cancer, hepatocellular cancer and lung cancer. Besides newer approaches and recent developments of 188)Re-labeled radioligands, no clinical results on the treatment response are yet available. In conclusion, several radioligands have been implemented on the basis of peptide receptor recognition throughout the last decade. A plentitude of preclinical data and clinical studies confirm their potential use in diagnosis as well as "proof-of-principle" for therapy of cancer patients. However, an optimal radiopeptide formulatioents. However, an optimal radiopeptide formulation does not yet exist for receptor-targeted radionuclide therapy. Ongoing developments may result in peptides more suitable for this kind of receptor-targeted radionuclide therapy.

  17. Indium-111 leukocyte imaging in patients with rheumatoid arthritis

    International Nuclear Information System (INIS)

    Uno, K.; Matsui, N.; Nohira, K.

    1986-01-01

    This study evaluates the usefulness of labeled leukocyte imaging in patients with rheumatoid arthritis. In 33 patients, the incidence of pain and swelling in 66 wrist joints and 66 knee joints was compared with the accumulation of [ 111 In]leukocytes. No accumulation of [ 111 In]leukocytes was seen in any of the patients' wrists (0/12) or knee joints (0/14) when both pain and swelling were absent. In contrast, 93% (25/27) of wrist joints and 80% (24/30) of knee joints with both pain and swelling were positive by [ 111 In]leukocyte scintigraphy. There was little correlation between the stage of the disease, as determined by radiography, and [ 111 In]leukocyte accumulation. This study suggests that [ 111 In]leukocyte imaging may be a reliable procedure for monitoring the activity of rheumatoid arthritis, especially for confirming the lack of an ongoing inflammatory response

  18. Indium-111 WBC detection of emphysematous gastritis in pancreatitis

    International Nuclear Information System (INIS)

    Caruana, V.; Swayne, L.C.; Salaki, J.S.

    1990-01-01

    We present a case of emphysematous gastritis initially detected with 111In oxine-labeled white blood cell scintigraphy and subsequently confirmed by computed tomography. Early aggressive antibiotic and supportive therapy resulted in a successful clinical outcome

  19. In vivo dissolution measurement with indium-111 summation peak ratios

    International Nuclear Information System (INIS)

    Jay, M.; Woodward, M.A.; Brouwer, K.R.

    1985-01-01

    Dissolution of [ 111 In]labeled tablets was measured in vivo in a totally noninvasive manner by using a modification of the perturbed angular correlation technique known as the summation peak ratio method. This method, which requires the incorporation of only 10-12 microCi into the dosage form, provided reliable dissolution data after oral administration of [ 111 In]lactose tablets. These results were supported by in vitro experiments which demonstrated that the dissolution rate as measured by the summation peak ratio method was in close agreement with the dissolution rate of salicylic acid in a [ 111 In]salicylic acid tablet. The method has the advantages of using only one detector, thereby avoiding the need for complex coincidence counting systems, requiring less radioactivity, and being potentially applicable to a gamma camera imaging system

  20. Scintigraphic detection of thrombi using indium-111-labeled autologous platelets

    International Nuclear Information System (INIS)

    Ikeoka, Kiyomitsu; Todo, Yasuhiro; Konishiike, Atsushi; Fujisue, Ryu; Ohyanagi, Mitsumasa; Yasutomi, Nagao; Tanimoto, Masaho; Kawai, Yoshitaka; Iwasaki, Tadaaki

    1985-01-01

    Intracardiac and arterial thrombi were examined by scintigraphy using In-111-oxine labeled autologous platelets. 1. In 22 cases of myocardial infarction including six with ventricular aneurysms, four had positive findings of thrombi on imaging and detected also by echocardiography. All four had ventricular aneurysms. The so-called ''moya-moya'' echoes (fuzzy echoes) were demonstrated in two of these four cases. 2. We encountered two cases with positive findings on imaging in 13 with mitral valve disease. These two had systemic embolic episodes after scintigraphic examination. ''Moya-moya'' echoes were detected in the left atrial cavity in four with negative findings on imaging. 3. Positive images were obtained in two of three with acute arterial occlusive disease, and in both cases platelet deposition was observed in the proximal site of obstruction. Though thrombectomy was performed for one of these two cases, no thrombus was detected at the site of platelet deposition. After one month, re-examination revealed only negative findings in all sites in both these patients. 4. In the six cases of aortic aneurysm, three had platelet deposition within their aneurysms, and surgery was performed for these positive cases, but one of them had no thrombus. 5. Positive images were obtained in only one of seven patients with chronic arterial occlusive disease. 6. Coagulation tests and platelet studies were investigated for patients with positive or negative platelet scans. Only the data of the thrombo-test showed a significant difference (97 +- 9 % vs 23 +- 7 %, p < 0.001). Three cases of positive imaging became negative after anticoagulant therapy. 7. We tried ECT for eight cases 24 hours after injection of In-111-oxine labeled platelets. Three cases showed clear images of thrombi, while the planar images could not detect them at an early stage. Therefore, we propose that ECT can be a useful technique for diagnosing intracardiac thrombi in early stage. (author)

  1. Clinical applications of indium-111-acetylacetone-labelled blood cells

    International Nuclear Information System (INIS)

    Georgi, P.; Sinn, H.; Wellman, H.; Clorius, J.H.; Becker, W.

    1981-01-01

    A method permitting red-cell labelling with 111 In-acetylacetone was reported in 1974 for evaluating intestinal blood loss, the liver-spleen ratio and the red-cell volume. White blood cells can be tagged similarly. In white-cell labelling, simultaneous red-cell or platelet tagging is avoided. Several procedures (dextran separation and gradient centrifugations) have been combined, to develop a highly selective cell separation. In osteomyelitis it may not be as advantageous to use 67 Ga-citrate, as in inflammatory soft tissue processes. The detection of inflammatory processes with labelled leukocytes could be of great importance for the scintigraphic diagnosis of osteomyelitidies. A group of 97 patients with suspected osteomyelitis have been examined using 111 In-acetylacetone-labelled leukocytes ( 111 In-AAL) immediately following positive routine skeletal scintigraphy. Images obtained 24 h post injection usually were the most satisfactory. In the followup group of 70 patients 21 true positives, 43 true negatives, 21 false negatives and 3 false positives were observed. These findings result in a specificity of 92%, sensitivity of 50% and accuracy of 70% with 111 In-AAL for osteomyelitis. Preliminary investigations using 111 In-acetylacetone-labelled thrombocytes ( 111 In-AAT) were carried out to detect rejection of transplanted kidneys. The platelets were separated by means of additional special density gradient centrifugations but no dextran from 15-20 ml of autologous whole blood. Scans have been obtained 15 min, 2.5 h and 24 h post injection in an initial group of 10 patients. In acute rejection, a high transplant uptake has been detected, whereas patients without acute rejection showed no or only a minimum activity accumulation. Patients with chronic rejection have intermediate uptakes

  2. Indium-111 leukocyte localization in infected prosthetic graft

    Energy Technology Data Exchange (ETDEWEB)

    Purnell, G.L.; Walker, C.W.; Allison, J.W.; Dalrymple, G.V. (Univ. of Arkansas for Medical Sciences, Little Rock (USA))

    1990-08-01

    Infective endocarditis can be difficult to prove, even in the face of strong clinical suspicion. A case in which standard methods of diagnosis failed to demonstrate endocarditis in a patient with recurrent Staphylococcus aureus bacteremia and porcine aortic valve is reported. An In-111 labelled leukocyte SPECT study demonstrated uptake in the aortic root and leaflets, and autopsy demonstrated vegetations on the leaflets. In-111 may prove useful in demonstrating endocarditis in patients with prosthetic valve infection.

  3. Indium-111 leukocyte localization in infected prosthetic graft

    International Nuclear Information System (INIS)

    Purnell, G.L.; Walker, C.W.; Allison, J.W.; Dalrymple, G.V.

    1990-01-01

    Infective endocarditis can be difficult to prove, even in the face of strong clinical suspicion. A case in which standard methods of diagnosis failed to demonstrate endocarditis in a patient with recurrent Staphylococcus aureus bacteremia and porcine aortic valve is reported. An In-111 labelled leukocyte SPECT study demonstrated uptake in the aortic root and leaflets, and autopsy demonstrated vegetations on the leaflets. In-111 may prove useful in demonstrating endocarditis in patients with prosthetic valve infection

  4. Indium-111 chloride imaging in the detection of infected prostheses

    International Nuclear Information System (INIS)

    Sayle, B.A.; Fawcett, H.D.; Wilkey, D.J.; Cierny, G. III; Mader, J.T.

    1985-01-01

    Thirty-three patients with painful joint prostheses and a suspicion of infection were imaged with [ 111 In]chloride. A final diagnosis was established by culture in 19. Of these, 12 were categorized as true positives and three as true negatives. There were two false-positive studies, occurring in patients with knee prostheses. In both, the culture was obtained by aspiration. The sensitivity was 86%, specificity 60%, and accuracy 79%. Seventeen of the proven cases had bone imaging prior to [ 111 In]chloride imaging. All 17 static images were positive and were not helpful in differentiating loosening from infection. Using increased uptake on the blood-pool image as a criteria for infection, the sensitivity was 89%, but the specificity was 0. Adding flow studies made little difference in interpreting the blood-pool images. This study shows that [ 111 In]chloride imaging is more accurate in evaluating infection in prosthesis than bone imaging

  5. Indium-111 granulocyte scintigraphy in inflammatory bowel disease

    International Nuclear Information System (INIS)

    Devillers, A.; Moisan, A.; Heresbach, D.; Darnault, P.; Bretagne, J.F.

    1996-01-01

    The present paper reports our experience since 1963 concerning 111-indium labeled autologous granulocytes scanning in the assessment of inflammatory bowel diseases and in the assessment of activity in Crohn's disease and ulcerative colitis. (authors). 94 refs., 3 figs

  6. Comparison of indium-111-oxine and indium-111-acetylacetone labelled leucocytes in the diagnosis of inflammatory disease

    Energy Technology Data Exchange (ETDEWEB)

    Peters, A.M.; Karimjee, S.; Saverymuttu, S.H.; Lavender, J.P. (Hammersmith Hospital, London (UK))

    1982-11-01

    /sup 111/In leucocyte scanning in a series of 132 patients has shown this technique to be a reliable and accurate means of diagnosing sepsis. Labelling with /sup 111/In oxine and with /sup 111/In acetylacetone gave similar values of sensitivity and specificity, and higher than those of ultrasound.

  7. [Investigations into the use of radiolabeled monoclonal antibodies for selective cell labeling in whole blood]: Progress report, March 1985-May 1988

    International Nuclear Information System (INIS)

    Thakur, M.L.

    1987-01-01

    Seventeen monoclonal antibodies (MAbs), 7 specific for human platelets and 10 specific for human polumorphonuclear leukocytes (PMNs) have been evaluated. One MAb has been identified as the antibody most suitable for canine platelets and another has been evaluted as the best among the group, for human neutrophil studies. Indium-111, Tc-99m, and I-125 have been used as the tracers. Six bifunctional chelating agents (BFCAs) were evaluated in order to determine the most efficient agent for maximal cell labeling efficiency. Among these, the DTPA has given us the best results. (4) To botain maximum In-111 chelation and minimum loss of the MAb affinity, the optimal BFCA to MAb ratios for both IgG and IgM type of MAbs were determined. Four different substances, stannous chloride, ascorbic acid, sodium dithionite and sodium borohydride, were evaluated as reducing agents for Tc-99m reduction and its optimal binding to MAbs. Dithionite at the concentration of 200 ug/ml DTPA-MAb solution provides greater than 50% Tc-99m labeling efficiency and maintains its immunospecificity equal to that of In-111-DTPA-MAb. The ability of radiolabeled MAb to interact with blood cells selectively in whole blood and with isolated blood cells was assessed and compared

  8. Monoclonal antibodies and cancer

    International Nuclear Information System (INIS)

    Haisma, H.J.

    1987-01-01

    The usefulness of radiolabeled monoclonal antibodies for imaging and treatment of human (ovarian) cancer was investigated. A review of tumor imaging with monoclonal antibodies is presented. Special attention is given to factors that influence the localization of the antibodies in tumors, isotope choice and methods of radiolabeling of the monoclonal antibodies. Two monoclonal antibodies, OC125 and OV-TL3, with high specificity for human epithelial ovarian cancer are characterized. A simple radio-iodination technique was developed for clinical application of the monoclonal antibodies. The behavior of monoclonal antibodies in human tumor xenograft systems and in man are described. Imaging of tumors is complicated because of high background levels of radioactivity in other sites than the tumor, especially in the bloodpool. A technique was developed to improve imaging of human tumor xenographs in nude mice, using subtraction of a specific and a non-specific antibody, radiolabeled with 111 In, 67 Ga and 131 I. To investigate the capability of the two monoclonal antibodies, to specifically localize in human ovarian carcinomas, distribution studies in mice bearing human ovarian carcinoma xenografts were performed. One of the antibodies, OC125, was used for distribution studies in ovarian cancer patients. OC125 was used because of availability and approval to use this antibody in patients. The same antibody was used to investigate the usefulness of radioimmunoimaging in ovarian cancer patients. The interaction of injected radiolabeled antibody OC125 with circulating antigen and an assay to measure the antibody response in ovarian cancer patients after injection of the antibody is described. 265 refs.; 30 figs.; 19 tabs

  9. Extracorporeal adsorption therapy: A Method to improve targeted radiation delivered by radiometal-labeled monoclonal antibodies

    International Nuclear Information System (INIS)

    Nemecek, Eneida R.; Green, Damian J.; Fisher, Darrell R.; Pagal, John M.; Lin, Yukang; Gopal, A. K.; Durack, Lawrence D.; Rajendran, Joseph G.; Wilbur, D. S.; Nilsson, Rune; Sandberg, Bengt; Press, Oliver W.

    2008-01-01

    antibody labeled with indium-111 (111In), seven patients received RIT with anti-CD20 antibody labeled with indium-111 for biokinetics and dosimetry, and therapeutic doses of antibody labeled with yttrium-90 (90Y). Performing the ECAT procedure at a rate that such that one blood volume per hour were circulated for 3 hours, resulted in mean radioactivity depletion of 96% in whole blood, 49% in whole body 49%, 62% in the lungs and 40% in liver and kidneys. There was no sufficient data to determine whether there was an improvement in the relative delivery of radiation to the tumor compared to normal organs by performing ECAT, but pharmacokinetic modeling studies suggested a potential therapeutic advantage using this approach. [refs] To evaluate the potential therapeutic advantages of ECAT, we performed biodistribution studies in nonhuman primates comparing the therapeutic ratios of radiation delivered using this approach to those delivered by conventional RIT alone. In addition, we evaluated lutetium-177 (177Lu) as an alternative isotope to optimize the delivery of RIT by improving the therapeutic index (target to non-target ratio)

  10. Monoclonal antibodies in oncology

    International Nuclear Information System (INIS)

    Chan, S.Y.T.; Sikora, K.

    1986-01-01

    Monoclonal antibodies (MCAs) can be used to differentiate between normal and neoplastic cells and thus exploited for diagnostic and, ultimately, therapeutic gain. The evidence for the existence of human tumour antigens is reviewed. Several areas of diagnosis are already benefiting from the application of the monoclonal technology. Immunohistology can help the pathologist with difficult diagnostic problems. New classifications of lymphoma and leukaemia can be based on specific surface molecules. Similarly, the detection of shed tumour antigens is already established as part of the routine assessment of many patients with common solid tumours. Isotopically labeled monoclonal antibodies have been used to localise primary and metastatic tumours. The use of antibodies in this way is not only a promising diagnostic tool but also the first step in studying the possibility of arming antibodies to provide therapeutic agents. Such trials are currently in progress. (Auth.)

  11. Monoclonal antibodies in myeloma

    DEFF Research Database (Denmark)

    Sondergeld, P.; van de Donk, N. W. C. J.; Richardson, P. G.

    2015-01-01

    The development of monoclonal antibodies (mAbs) for the treatment of disease goes back to the vision of Paul Ehrlich in the late 19th century; however, the first successful treatment with a mAb was not until 1982, in a lymphoma patient. In multiple myeloma, mAbs are a very recent and exciting add...

  12. Vascular targeted therapy with anti-prostate-specific membrane antigen monoclonal antibody J591 in advanced solid tumors.

    Science.gov (United States)

    Milowsky, Matthew I; Nanus, David M; Kostakoglu, Lale; Sheehan, Christine E; Vallabhajosula, Shankar; Goldsmith, Stanley J; Ross, Jeffrey S; Bander, Neil H

    2007-02-10

    Based on prostate-specific membrane antigen (PSMA) expression on the vasculature of solid tumors, we performed a phase I trial of antibody J591, targeting the extracellular domain of PSMA, in patients with advanced solid tumor malignancies. This was a proof-of-principle evaluation of PSMA as a potential neovascular target. The primary end points were targeting,toxicity, maximum-tolerated dose, pharmacokinetics (PK), and human antihuman antibody (HAHA) response. Patients had advanced solid tumors previously shown to express PSMA on the neovasculature. They received 111Indium (111ln)-J591 for scintigraphy and PK, followed 2 weeks later by J591 with a reduced amount of 111In for additional PK measurements. J591 dose levels were 5, 10, 20, 40, and 80 mg. The protocol was amended for six weekly administrations of unchelated J591. Patients with a response or stable disease were eligible for re-treatment. Immunohistochemistry assessed PSMA expression in tumor tissues. Twenty-seven patients received monoclonal antibody (mAb) J591. Treatment was well tolerated. Twenty (74%) of 27 patients had at least one area of known metastatic disease targeted by 111In-J591, with positive imaging seen in patients with kidney, bladder, lung, breast, colorectal, and pancreatic cancers, and melanoma. Seven of 10 patient specimens available for immunohistochemical assessment of PSMA expression in tumor-associated vasculature demonstrated PSMA staining. No HAHA response was seen. Three patients of 27 with stable disease received re-treatment. Acceptable toxicity and excellent targeting of known sites of metastases were demonstrated in patients with multiple solid tumor types, highlighting a potential role for the anti-PSMA antibody J591 as a vascular-targeting agent.

  13. {sup 99m}Tc-annexin V and {sup 111}In-antimyosin antibody uptake in experimental myocardial infarction in rats

    Energy Technology Data Exchange (ETDEWEB)

    Sarda-Mantel, Laure; Rouzet, Francois; Martet, Genevieve; Raguin, Olivier; Vrigneaud, Jean-Marc; Guludec, Dominique Le [Bichat Hospital AP-HP, EA 3512, Nuclear Medicine Department, Paris (France); Michel, Jean-Baptiste; Louedec, Liliane [INSERM U460, UFR Bichat, Paris (France); Vanderheyden, Jean-Luc [Theseus Imaging Corporation, Boston, MA (United States); Hervatin, Florence [Bichat Hospital AP-HP, EA 3512, Nuclear Medicine Department, Paris (France); CGA/SHFS, Orsay (France); Khaw, Ban An [Bouve College of Pharmacy and Health Sciences, Center for Drug Targeting and Analysis, Boston, MA (United States)

    2006-03-15

    {sup 99m}Tc-annexin V (ANX) allows scintigraphic detection of apoptotic cells via specific binding to exposed phosphatidylserine. In myocardial infarction, apoptosis of myocytes is variable and depends especially on the presence or absence of coronary reperfusion. In this study, ANX uptake in non-reperfused experimental myocardial infarcts was compared with uptake of a marker of myocyte necrosis ({sup 111}In-antimyosin antibodies, AM) and an immunohistochemical marker of apoptosis (Apostain). The left anterior coronary artery was ligated in 47 Wistar rats, which were then injected with ANX (n=20), AM (n=21) or both (n=6). Myocardial uptake of ANX and AM was determined at 2 h (n=14), 4 h (n=14) and 24 h (n=19) after coronary ligation (CL), by quantitative autoradiography with (n=23) or without (n=24) gamma imaging. Heart-to-lung ratios (HLRs) and infarct-to-remote myocardium activity ratios (INRs) were calculated on the scintigrams and autoradiograms respectively. Cardiac sections were stained with haematoxylin-eosin and Apostain. The above studies were repeated in 12 normal rats. All rats with CL showed increased ANX and AM uptake in cardiac areas on scintigrams 24 h after CL, with HLRs higher than in controls: 3.1{+-}0.6 versus 1.5{+-}0.3 (p=0.001) for ANX and 1.99{+-}0.44 versus 1.01{+-}0.05 (p<0.0005) for AM. Autoradiography showed intense ANX and AM uptake in infarcts, with comparable topography and INRs at 2 h, 4 h and 24 h after CL (4.6{+-}0.9 versus 5.0{+-}1.8 at 24 h), while Apostain staining was very low (0.06{+-}0.06% of cells). In this model of persistent CL, we observed increased ANX uptake in injured myocardium, comparable in intensity, topography and kinetics to that of AM. There was only minimal Apostain staining in the same areas. (orig.)

  14. Monoclonal antibodies to Pneumocystis carinii

    DEFF Research Database (Denmark)

    Kovacs, J A; Halpern, J L; Lundgren, B

    1989-01-01

    To increase understanding of the antigenic structure of Pneumocystis carinii, we developed monoclonal antibodies to rat and human P. carinii. The specificity of the antibodies was demonstrated by immunofluorescence and immunoblot studies. Only one of five monoclonal antibodies to rat P. carinii r...

  15. Phase I trial of yttrium-90-labeled anti-prostate-specific membrane antigen monoclonal antibody J591 for androgen-independent prostate cancer.

    Science.gov (United States)

    Milowsky, Matthew I; Nanus, David M; Kostakoglu, Lale; Vallabhajosula, Shankar; Goldsmith, Stanley J; Bander, Neil H

    2004-07-01

    To determine the maximum-tolerated dose (MTD), toxicity, human antihuman antibody (HAHA) response, pharmacokinetics, organ dosimetry, targeting, and preliminary efficacy of yttrium-90-labeled anti-prostate-specific membrane antigen monoclonal antibody J591 ((90)Y-J591) in patients with androgen-independent prostate cancer (PC). Patients with androgen-independent PC and evidence of disease progression received indium-111-J591 for pharmacokinetic and biodistribution determinations followed 1 week later by (90)Y-J591 at five dose levels: 5, 10, 15, 17.5, and 20 mCi/m(2). Patients were eligible for up to three re-treatments if platelet and neutrophil recovery was satisfactory. Twenty-nine patients with androgen-independent PC received (90)Y-J591, four of whom were re-treated. Dose limiting toxicity (DLT) was seen at 20 mCi/m(2), with two patients experiencing thrombocytopenia with non-life-threatening bleeding episodes requiring platelet transfusions. The 17.5-mCi/m(2) dose level was determined to be the MTD. No re-treated patients experienced DLT. Nonhematologic toxicity was not dose limiting. Targeting of known sites of bone and soft tissue metastases was seen in the majority of patients. No HAHA response was seen. Antitumor activity was seen, with two patients experiencing 85% and 70% declines in prostate-specific antigen (PSA) levels lasting 8 and 8.6 months, respectively, before returning to baseline. Both patients had objective measurable disease responses. An additional six patients (21%) experienced PSA stabilization. The recommended dose for (90)Y-J591 is 17.5 mCi/m(2). Acceptable toxicity, excellent targeting of known sites of PC metastases, and biologic activity in patients with androgen-independent PC warrant further investigation of (90)Y-J591 in the treatment of patients with PC.

  16. In vivo targeting of dead tumor cells in a murine tumor model using a monoclonal antibody specific for the La autoantigen.

    Science.gov (United States)

    Al-Ejeh, Fares; Darby, Jocelyn M; Pensa, Katherine; Diener, Kerrilyn R; Hayball, John D; Brown, Michael P

    2007-09-15

    To investigate the potential of the La-specific monoclonal antibody (mAb) 3B9 as an in vivo tumor-targeting agent. The murine EL4 lymphoma cell line was used for in vitro studies and the EL4 model in which apoptosis was induced with cyclophosphamide and etoposide was used for in vivo studies. In vitro studies compared 3B9 binding in the EL4 cell with that in its counterpart primary cell type of the thymocyte. For in vivo studies, 3B9 was intrinsically or extrinsically labeled with carbon-14 or 1,4,7,10-tetra-azacylododecane-N,N',N'',N''''-tetraacetic acid-indium-111, respectively, and biodistribution of the radiotracers was investigated in EL4 tumor-bearing mice, which were treated or not with chemotherapy. La-specific 3B9 mAb bound EL4 cells rather than thymocytes, and binding was detergent resistant. 3B9 binding to dead EL4 cells in vitro was specific, rapid, and saturable. Significantly, more 3B9 bound dead EL4 tumor explant cells after host mice were treated with chemotherapy, which suggested that DNA damage induced 3B9 binding. Tumor binding of 3B9 in vivo was antigen specific and increased significantly after chemotherapy. Tumor accumulation of 3B9 peaked at approximately 50% of the injected dose per gram of tumor 72 h after chemotherapy and correlated with increased tumor cell death. Tumor/organ ratios of 3B9 biodistribution, which included the tumor/blood ratio, exceeded unity 48 or more hours after chemotherapy. La-specific mAb selectively targeted dead tumor cells in vivo, and targeting was augmented by cytotoxic chemotherapy. This novel cell death radioligand may be useful both for radioimmunoscintigraphy and radioimmunotherapy.

  17. APOMAB, a La-specific monoclonal antibody, detects the apoptotic tumor response to life-prolonging and DNA-damaging chemotherapy.

    Directory of Open Access Journals (Sweden)

    Fares Al-Ejeh

    Full Text Available BACKGROUND: Antineoplastic therapy may impair the survival of malignant cells to produce cell death. Consequently, direct measurement of tumor cell death in vivo is a highly desirable component of therapy response monitoring. We have previously shown that APOMAB representing the DAB4 clone of a La/SSB-specific murine monoclonal autoantibody is a malignant cell-death ligand, which accumulates preferentially in tumors in an antigen-specific and dose-dependent manner after DNA-damaging chemotherapy. Here, we aim to image tumor uptake of APOMAB (DAB4 and to define its biological correlates. METHODOLOGY/PRINCIPAL FINDINGS: Brisk tumor cell apoptosis is induced in the syngeneic EL4 lymphoma model after treatment of tumor-bearing mice with DNA-damaging cyclophosphamide/etoposide chemotherapy. Tumor and normal organ accumulation of Indium 111 ((111In-labeled La-specific DAB4 mAb as whole IgG or IgG fragments was quantified by whole-body static imaging and organ assay in tumor-bearing mice. Immunohistochemical measurements of tumor caspase-3 activation and PARP-1 cleavage, which are indicators of early and late apoptosis, respectively, were correlated with tumor accumulation of DAB4. Increased tumor accumulation of DAB4 was associated directly with both the extent of chemotherapy-induced tumor cell death and DAB4 binding per dead tumor cell. Tumor DAB4 accumulation correlated with cumulative caspase-3 activation and PARP-1 cleavage as tumor biomarkers of apoptosis and was directly related to the extended median survival time of tumor-bearing mice. CONCLUSIONS/SIGNIFICANCE: Radiolabeled La-specific monoclonal antibody, DAB4, detected dead tumor cells after chemotherapy, rather than chemosensitive normal tissues of gut and bone marrow. DAB4 identified late apoptotic tumor cells in vivo. Hence, radiolabeled DAB4 may usefully image responses to human carcinoma therapy because DAB4 would capture the protracted cell death of carcinoma. We believe that the

  18. Dissecting Immunogenicity of Monoclonal Antibodies

    National Research Council Canada - National Science Library

    Snyder, Christopher

    2003-01-01

    The potential of monoclonal antibodies, (mAbs), for use in therapeutic and diagnostic applications has not been fully realized in part due to counter-immune responses that often arise in patient recipients of mAb...

  19. Comparative studies of 111In-labeled monoclonal antibody using spacer-containing and non-spacer bifunctional chelates. 2

    International Nuclear Information System (INIS)

    Sun, Baofu

    1994-01-01

    Indium-111-labeled A7 monoclonal antibodies using two spacer-containing chelates, succinimido-EGS-DTPA (EGS-DTPA: diester spacer) and maleimido-C10-Bz-EDTA (C10-Bz-EDTA: hydrocarbon spacer) were investigated in human LS180 colon tumor bearing nude mice and were compared with two non-spacer chelates, cyclic DTPA dianhydride (cDTPAA) and isothiocyanatobenzyl-EDTA (SCN-Bz-EDTA). Compared with immunoconjugates using non-spacer chelates, immunoconjugates using spacer-containing chelates, especially C10-Bz-EDTA-A7 showed lower 111 In activity in normal organs. The radioactivity in the liver for C10-Bz-EDTA-A7 decreased continuously till 96 hrs postinjection, however, this liver radioactivity for EGS-DTPA-A7 showed little change after 24 hrs. Moreover, in liver subcellular distribution study, EGS-DTPA-A7 showed a higher activity retention in mitochondrial fraction which contained lysosome, a place for metabolizing and storing of 111 In labeled antibody, than that of C10-Bz-EDTA-A7. The C10-Bz-EDTA-A7 conjugate demonstrated more preferable tumor-to-non tumor contrast on the scintigrams than that found with other three immunoconjugates. Up to 96 hrs postinjection, tumor bearing nude mice injecting with immunoconjugates using spacer-containing chelates exreted twice radioactivity from whole body than that excreted by using non-spacer chelates. Interestingly, different from other three chelates, C10-Bz-EDTA-A7 were mainly excreted via feces. We conclude that the decrease of radioactivity in normal tissues in the case of EGS-DTPA-A7 was due to the rapid decrease of activity in the blood, while in the case of C10-Bz-EDTA-A7 it was due to the quickly excreted small metabolite through faces. 111 In labeled C10-Bz-EDTA conjugate is superior, at least when conjugated with A7, to other three chelate conjugates used in this study. (author)

  20. Uses of monoclonal antibody 8H9

    Science.gov (United States)

    Cheung, Nai-Kong V.

    2013-04-09

    This invention provides a composition comprising an effective amount of monoclonal antibody 8H9 or a derivative thereof and a suitable carrier. This invention provides a pharmaceutical composition comprising an effective amount of monoclonal antibody 8H9 or a derivative thereof and a pharmaceutically acceptable carrier. This invention also provides an antibody other than the monoclonal antibody 8H9 comprising the complementary determining regions of monoclonal antibody 8H9 or a derivative thereof, capable of binding to the same antigen as the monoclonal antibody 8H9. This invention provides a substance capable of competitively inhibiting the binding of monoclonal antibody 8H9. This invention also provides an isolated scFv of monoclonal antibody 8H9 or a derivative thereof. This invention also provides the 8H9 antigen. This invention also provides different uses of the monoclonal antibody 8H9 or its derivative.

  1. Tumor imaging with monoclonal antibodies

    International Nuclear Information System (INIS)

    Haisma, H.; Hilgers, J.

    1987-01-01

    Many monoclonal antibodies directed against tumor-associated antigens have been identified, but so far none of these are tumor specific. Polyclonal and monoclonal antibodies have been used for imaging of a wide variety of tumors with success. Radiolabeling of antibody is usually done with iodine isotopes of which 123 I is the best candidate for radioimmunodetection purposes. The labeling of antibodies through chelates makes it possible to use metal radioisotopes like 111 In, which is the best radioisotope for imaging with monoclonal antibodies due to its favorable half-life of 2.5 days. Usually imaging cannot be performed within 24 h after injection, but clearance of antibody can be increased by using F(ab) 2 of Fab. Another approach is to clear non-bound antibody by a second antibody, directed against the first. The detection limit of immunoimaging is about 2 cm, but will be improved by tomography or SPECT. There is still a high false positive and false negative rate, which makes it impossible to use radioimmunodetection as the only technique for diagnosis of tumors. In combination with other detection techniques, tumor imaging with monoclonal antibodies can improve diagnosis. 44 refs.; 3 tabs

  2. Radiolabeled monoclonal antibodies: a review

    International Nuclear Information System (INIS)

    Toledo e Souza, I.T. de; Okada, H.

    1990-05-01

    Since the description by Kohler and Milstein 1975 of their technique for producing monoclonal antibodies of predefined specificity, it has become a mainstay in most laboratories that utilize immunochemical techniques to study problems in basic, applied or clinical research. Paradoxically, the very success of monoclonal antibodies has generated a literature which is now so vast and scattered that it has become difficult to obtain a perspective. This brief review represents the distillation of many publications relating to the production and use of monoclonaal antibodies as radiopharmaceuticals. Significant advances were made possible in the last few years by combined developments in the fields of tumor-associated antigens and of monoclonal antibodies. In fact monoclonal antibodies against some well defined tumor-associated antigens, has led to significantly greater practical possibilities for producing highly specific radiolabeled antibodies as radiopharmaceuticals for diagnosis and therapy of human tumors. One of the main requirements of this methodology is the availability of stable radiopharmaceutical reagents which after labeling in vivo injection retain the capacity of specific interaction with the defined antigen and their molecular integrity. Since injection into human is the objetive of this kind of study all the specifications of radiopharmaceutical have to be fulfilled e.g. sterility, apirogenicity and absence of toxicity. (author) [pt

  3. The value of gamma camera and computed tomography data set coregistration to assess Lewis Y antigen targeting in small cell lung cancer by 111Indium-labeled humanized monoclonal antibody 3S193

    International Nuclear Information System (INIS)

    Quaia, Emilio; Krug, Lee M.; Pandit-Taskar, Neeta; Nagel, Andrew; Reuter, Victor E.; Humm, John; Divgi, Chaitanya

    2008-01-01

    Aim: To assess the value of data set coregistration of gamma camera and computed tomography (CT) in the assessment of targeting of humanized monoclonal antibody 3S193 labeled with indium-111 ( 111 In-hu3S193) to small cell lung cancer (SCLC). Methods and materials: Ten patients (6 male and 4 female; mean age ± S.D., 60 ± 4 years), from an overall population of 20 patients with SCLCs expressing Lewis Y antigen at immunohistochemical analysis, completed a four weekly injections of 111 In-hu3S193 and underwent gamma camera imaging. All had had, as part of their baseline evaluation, Fluorine18 fluoro-2-deoxyglucose (FDG) positron emission tomography/computed tomography (PET/CT). Two readers in consensus retrospectively coregistered the gamma camera images with the CT component of the FDG PET/CT by automatic or manual alignment. The resulting image sets were visually examined and SCLC lesions targeting at coregistered gamma camera and CT was correlated side-by-side with the 18 F-FDG uptake. Results: A total number of 31 lesions from SCLC with a thoracic (n = 13) or extrathoracic location (n = 18) were all positive on FDG PET/CT. Coregistration of the gamma camera to the CT demonstrated targeting of antibody to all lesions >2 cm (n = 20) and in a few lesions ≤2 cm (n = 2), with no visualization of most lesions ≤2 cm (n = 9). No 111 In-hu3S193 uptake in normal tissues was observed. Conclusion: Coregistration of antibody gamma camera imaging to FDG PET/CT is feasible and allows valuable assessment of 111 In-hu3S193 antibody targeting to SCLC lesions >2 cm, while lesions ≤2 cm reveal a limited targeting

  4. Monoclonal antibodies technology. Protocols

    International Nuclear Information System (INIS)

    Acevado Castro, B.E.

    1997-01-01

    Full text: Immunization. The first step in preparing useful monoclonal antibodies (MAbs) is to immunize an animal (Balb/c for example) with an appropriate antigen. Methods (only for soluble antigen): Solubilize selected antigen in Phosphate buffer solution (PBS) at pH 7.2-7.4, ideally at a final concentration per animal between 10 to 50 μg/ml. It is recommended that the antigen under consideration be incorporated into the emulsion adjuvants in 1:1 volumetric relation. We commonly use Frend's adjuvant (FA) to prepared immunized solution. The first immunization should be prepared with complete FA, and the another could be prepared with incomplete FA. It is recommended to inject mice with 0.2 ml intraperitoneal (ip) or subcutaneous (sc). Our experience suggests the sc route is the preferred route. A minimum protocol for immunizing mice to generate cells for preparing hybridomas is s follows: immunize sc on day 0, boost sc on day 21, take a trial bleeding on day 26; if antibody titters are satisfactory, boost ip on day 35 with antigen only, and remove the spleen to obtain cells for fusion on day 38. Fusion protocol. The myeloma cell line we are using is X63 Ag8.653. At the moment of fusion myeloma cells need a good viability (at least a 95%). 1. Remove the spleen cells from immunized mice using sterile conditions. An immune spleen should yield between 7 a 10x10 7 nucleated cells. 2. Place the spleen in 20 ml of serum-free RPMI 1640 in a Petri dish. Using a needle and syringe, inject the spleen with medium to distend and disrupt the spleen stroma and free the nucleated cells. 3. Flush the cell suspension with a Pasteur pipet to disperse clumps of cells. 4. Centrifuge the spleen cell suspension at 250g for 10 min. Resuspend the pellet in serum-free RPMI 1640. Determine cell concentration using Neuhabuer chamber. 5. Mix the myeloma cells and spleen cells in a conical 50-ml tube in serum-free RPMI 1640, 1 x10 7 spleen cells to 1x10 6 myeloma cells (ratio 10:1). Centrifuge

  5. Production of Monoclonal Antibodies specific for Progesterone

    OpenAIRE

    YÜCEL, Fatıma

    2014-01-01

    Progesterone levels in milk and serum are indicators of pregnancy in cattle. The progesterone level reaches a peak on the 21 st and 22 nd days of pregnancy. Monoclonal antibodies specific to progesterone could be used for the immunodetection of milk and serum progesterone levels. We report here the development of hybrid cells prdoducing monoclonal antibodies specific for progesterone using hybridoma technology. Hybridoma cells secreting monoclonal antibodies against progesterone (MAM 2H1...

  6. Monoclonal antibodies for treating cancer

    International Nuclear Information System (INIS)

    Dillman, R.O.

    1989-01-01

    The purpose of this study is to assess the current status of in-vivo use of monoclonal antibodies for treating cancer. Publications appearing between 1980 and 1988 were identified by computer searches using MEDLINE and CANCERLIT, by reviewing the table of contents of recently published journals, and by searching bibliographies of identified books and articles. More than 700 articles, including peer-reviewed articles and book chapters, were identified and selected for analysis. The literature was reviewed and 235 articles were selected as relevant and representative of the current issues and future applications for in-vivo monoclonal antibodies for cancer therapy and of the toxicity and efficacy which has been associated with clinical trials. Approaches include using antibody alone (interacting with complement or effector cells or binding directly with certain cell receptors) and immunoconjugates (antibody coupled to radioisotopes, drugs, toxins, or other biologicals). Most experience has been with murine antibodies. Trials of antibody alone and radiolabeled antibodies have confirmed the feasibility of this approach and the in-vivo trafficking of antibodies to tumor cells. However, tumor cell heterogeneity, lack of cytotoxicity, and the development of human antimouse antibodies have limited clinical efficacy. Although the immunoconjugates are very promising, heterogeneity and the antimouse immune response have hampered this approach as has the additional challenge of chemically or genetically coupling antibody to cytotoxic agents. As a therapeutic modality, monoclonal antibodies are still promising but their general use will be delayed for several years. New approaches using human antibodies and reducing the human antiglobulin response should facilitate treatment. 235 references

  7. Monoclonal antibody-based immunoassays.

    Science.gov (United States)

    Appleby, P; Reischl, U

    1998-01-01

    An immunoassay may be defined as an assay that employs an immunological reagent, usually an antibody, to confer specificity for the ligand being measured. As a corollary to this, the discovery, and subsequent development, of monoclonal antibodies (MAbs) has greatly expanded the application and use of immunoassays. Polyclonal reagents, with their associated problems of specificity and quality control, have now been largely replaced by readily available MAbs of potential immortality and well-defined specificity and affinity. This has resulted, in the last two decades, in a great expansion in the range of immunoassays available and also a significant improvement in their reproducibility and reliability.

  8. Uses of monoclonal antibody 8H9

    Energy Technology Data Exchange (ETDEWEB)

    Cheung, Nai-Kong V.

    2018-04-10

    This invention provides a composition comprising an effective amount of monoclonal antibody 8H9 or a derivative thereof and a suitable carrier. This invention provides a pharmaceutical composition comprising an effective amount of monoclonal antibody 8H9 or a derivative thereof and a pharmaceutically acceptable carrier. This invention also provides an antibody other than the monoclonal antibody 8H9 comprising the complementary determining regions of monoclonal antibody 8H9 or a derivative thereof, capable of binding to the same antigen as the monoclonal antibody 8H9. This invention provides a substance capable of competitively inhibiting the binding of monoclonal antibody 8H9. This invention also provides an isolated scFv of monoclonal antibody 8H9 or a derivative thereof. This invention also provides the 8H9 antigen. This invention also provides a method of inhibiting the growth of tumor cells comprising contacting said tumor cells with an appropriate amount of monoclonal antibody 8H9 or a derivative thereof.

  9. Platelet kinetics with indium-111 platelets: comparison with chromium-51 platelets

    International Nuclear Information System (INIS)

    Peters, A.M.; Lavender, J.P.

    1983-01-01

    The application of 111In-oxine to platelet labeling has contributed to the understanding of platelet kinetics along three lines: 1. It allows the measurement of new parameters of splenic function, such as the intrasplenic platelet transit time, which has shed new light on the physiology of splenic blood cell handling. 2. It facilitates the measurement of platelet life span in conditions, such as ITP, in which 51Cr may undergo undesirable elution from the platelet as a result of platelet-antibody interaction. 3. It allows the determination of the fate of platelets, that is, the site of platelet destruction in conditions in which reduced platelet life span is associated with abnormal platelet consumption, as a result of either premature destruction of ''abnormal'' platelets by the RE system, or the consumption (or destruction) of normal platelets after their interaction with an abnormal vasculature. Future research using 111In platelets may yield further valuable information on the control as well as the significance of intrasplenic platelet pooling, on the role of platelets in the development of chronic vascular lesions, and on the sites of platelet destruction in ITP. With regard to the latter, methods will have to be developed for harvesting sufficient platelets representative of the total circulating platelet population from severely thrombocytopenic patients for autologous platelet labeling. This would avoid the use of homologous platelets, which is likely to be responsible for some of the contradictory data relating to the use of radiolabeled platelet studies for the prediction of the response of patients with ITP to splenectomy

  10. Indium-111 leukocyte scintigraphic detection of myocardial abscess formation in patients with endocarditis

    Energy Technology Data Exchange (ETDEWEB)

    Cerqueira, M.D.; Jacobson, A.F.

    1989-05-01

    Myocardial abscess formation in patients with bacterial endocarditis in most clinical settings, especially in patients with prosthetic valves, is a primary indicator for surgical valve replacement. We report the detection of myocardial abscesses using /sup 111/In leukocyte scintigraphy in three patients with prosthetic or native valve endocarditis and nondiagnostic echocardiograms. Leukocyte scintigraphy may allow identification of myocardial abscess formation earlier than other imaging modalities.

  11. Kinetic study of indium-111 labelled platelets in idiopathic thrombocytopenic purpura

    International Nuclear Information System (INIS)

    Reiffers, J.; Vuillemin, L.; Broustet, A.; Ducassou, D.

    1982-01-01

    Labelling platelets with 111 Indium-oxine has advantages over the conventional 51 chromium method: labelling is more efficient and the radiations emitted almost exclusively consist of gamma-rays. Owing to these advantages, autologous platelets can be used for kinetic studies in patients with idiopathic thrombocytopenic purpura, even when thrombocytopenia is severe. 111 Indium labelling also provides accurate information on the sites of platelet destruction, which may help to predict the patient's response to splenectomy [fr

  12. Platelet destruction in autoimmune thrombocytopenic purpura: kinetics and clearance of indium-111-labeled autologous platelets

    International Nuclear Information System (INIS)

    Stratton, J.R.; Ballem, P.J.; Gernsheimer, T.; Cerqueira, M.; Slichter, S.J.

    1989-01-01

    Using autologous 111 In-labeled platelets, platelet kinetics and the sites of platelet destruction were assessed in 16 normal subjects (13 with and three without spleens), in 17 studies of patients with primary autoimmune thrombocytopenic purpura (AITP), in six studies of patients with secondary AITP, in ten studies of patients with AITP following splenectomy, and in five thrombocytopenic patients with myelodysplastic syndromes. In normal subjects, the spleen accounted for 24 +/- 4% of platelet destruction and the liver for 15 +/- 2%. Untreated patients with primary AITP had increased splenic destruction (40 +/- 14%, p less than 0.001) but not hepatic destruction (13 +/- 5%). Compared with untreated patients, prednisone treated patients did not have significantly different spleen and liver platelet sequestration. Patients with secondary AITP had similar platelet counts, platelet survivals, and increases in splenic destruction of platelets as did patients with primary AITP. In contrast, patients with myelodysplastic syndromes had a normal pattern of platelet destruction. In AITP patients following splenectomy, the five nonresponders all had a marked increase (greater than 45%) in liver destruction compared to five responders (all less than 40%). Among all patients with primary or secondary AITP, there was an inverse relationship between the percent of platelets destroyed in the liver plus spleen and both the platelet count (r = 0.75, p less than 0.001) and the platelet survival (r = 0.86, p less than 0.001). In a stepwise multiple linear regression analysis, total liver plus spleen platelet destruction, the platelet survival and the platelet turnover were all significant independent predictors of the platelet count. Thus platelet destruction is shifted to the spleen in primary and secondary AITP. Failure of splenectomy is associated with a marked elevation in liver destruction

  13. Splenic dynamics of indium-111 labeled platelets in idiopathic thrombocytopenic purpura

    International Nuclear Information System (INIS)

    Syrjaelae, M.T.Sa.; Savolainen, S.; Nieminen, U.; Gripenberg, J.; Liewendahl, K.; Ikkala, E.

    1989-01-01

    Splenic dynamics of 111 In-labeled platelets and platelet-associated IgG in 33 patients with idiopathic thrombocytopenic purpura (ITP) were studied. Two half-lives were calculated for the biexponential splenic time-activity curve after i.v. injection of 111 In-labeled platelets. There was no difference in the mean half-life of the rapid component of the splenic curve (ST1) when patients with negative or slightly positive platelet suspension immunofluorescence test (PSIFT) were compared to those with strongly positive PSIFT (3.0 ± 0.7 min vs. 3.6 ± 0.4, p greater than 0.05). Mean half-life of the slow component of the splenic curve (ST2) was found to be longer in patients with a strongly positive than a negative or weakly positive PSIFT (26 ± 5 min vs. 13.2 ± 1.0 min, p less than 0.01). It seems that determination of the two components of the splenic time-activity curve provides a useful method for studying platelet kinetics in ITP

  14. The effects of indium-111 decay on pBR322 DNA

    International Nuclear Information System (INIS)

    Sahu, S.K.; Adelstein, S.J.; Makrigiorgos, G.M.; Baranowska-Kortylewicz, J.

    1995-01-01

    We have compared the effectiveness in causing DNA strand breaks of 111 In bound to DNA or free in aqueous solution with that of γ rays. Supercoiled DNA from pBR322 plasmid labeled with [ 3 H]thymidine was purified and mixed with 111 InCl 3 in the absence of presence of diethylenetriaminepentaacetic dianhydride (DTPA), a metal chelator which prevents the binding of indium to DNA. The reaction mixtures were stored at 4 degrees C to accumulate radiation dose from the decay of 111 In. The DNA was then resolved by gel electrophoresis into supercoiled, nicked circular and linear forms, representing undamaged DNA, single-strand breaks (SSBs) and double-strand breaks (DSBs), respectively. The D o values of pBR322 DNA exposed to γ radiation from an external 137 Cs source and the decay of 111 In dispersed in solution (+DTPA) are 3.1 ± 0.1 and 2.8 ± 0.1 Gy, respectively. In terms of accumulated 111 In disintegrations cm -3 of plasmid DNA solution, the D o value is 15.3 (± 0.7) x 10 10 disintegrations in the absence of DTPA and 38.2 (± 1.1) x 10 10 disintegrations in its presence. Since only 14.6 ± 5% of the 111 In was bound to DNA in the absence of DTPA, an effective D o for bound 111 In of 3.4 (± 1.1) x 10 10 disintegrations is obtained. The 11-fold (range 9- to 17-fold) increased effectiveness of this Auger electron emitter when in proximity to DNA appears to be due mainly to the higher yield of SSBs. 34 refs., 4 figs., 3 tabs

  15. Colonic localization of indium-111 labeled leukocytes in active Behcet's disease

    International Nuclear Information System (INIS)

    Harre, R.G.; Conrad, G.R.; Seabold, J.E.

    1988-01-01

    A patient with known Behcet's disease demonstrated intense colonic localization of In-111 labeled leukocytes. Gastrointestinal involvement had not been previously manifested, but extensive colonic inflammation was documented by endoscopy. This case illustrates the utility of In-111 labeled leukocyte imaging for detecting active bowel disease in a debilitated patient with documented Behcet's vasculitis

  16. Labeling with indium-111 has detrimental effects on human lymphocytes: concise communication

    NARCIS (Netherlands)

    ten Berge, R. J.; Natarajan, A. T.; Hardeman, M. R.; van Royen, E. A.; Schellekens, P. T.

    1983-01-01

    When lymphocytes from human peripheral blood were labeled with In-111 oxinate, several of their properties appeared to be affected. The spontaneous release of the radionuclide was found to be relatively high. Labeled lymphocytes showed a decreased proliferative capacity, dependent on the dose of the

  17. Indium-111 labeled leukocyte images demonstrating a lung abscess with prominent fluid level

    International Nuclear Information System (INIS)

    Massie, J.D.; Winer-Muram, H.

    1986-01-01

    In-111 labeled leukocyte images show an abscess cavity with a fluid level on 24-hour upright images. Fluid levels, frequently seen on radiographs, are uncommon on nuclear images. This finding demonstrates rapid migration of labeled leukocytes into purulent abscess fluid

  18. Use of indium-111-oxinate-labelled granulocytes and thrombocytes in kidney transplantation

    International Nuclear Information System (INIS)

    Royen, E.A. van; Schoot, J.B. van der; Hardeman, M.R.; Surachno, S.; Veen, J.H. ten; Vreeken, J.; Wilmink, J.M.

    1981-01-01

    The diagnostic use of 111 In-oxinate-labelled granulocytes and thrombocytes in kidney graft rejection was studied in 39 transplant patients. Normal values were established for the deposition of these cells in stable, functioning kidney grafts. Although some 111 In granulocyte accumulation occurred in the graft during rejection, the increase was too slight to render the method suitable for the early diagnosis of rejection. Significant increased 111 In thrombocyte deposition was found during rejection periods, although large differences were observed in the degree of accumulation. Severity or type of rejection may relate to these differences. Post-transplantation follow-up by 111 In thrombocyte scintigraphy did not result in a much earlier diagnosis of rejection than classic clinical signs. However, more frequent bedside activity determinations might do so. (author)

  19. Utility of indium-111 labelled autologous platelets in the diagnosis of renal graft rejection

    International Nuclear Information System (INIS)

    Martin-Comin, J.; Roca, M.; Grino, J.M.; Paradell, C.; Caralps, A.

    1982-01-01

    The usefulness of In-111 labelled autologous platelets in the diagnosis of renal graft rejection was studied. The method is based on imaging of the graft area at 4, 24, 48 and 72 hours after the injection of the labelled cells. The study was done in 21 renal cadaveric transplant recipients: control group: four patients without evidence of rejection. No platelet uptake was observed in any of them. Study group: in 13 patients with acute rejection and 1 with chronic rejection graft tracer uptake was seen. In the 3 others with a non-immunological sudden impairment of renal function, no activity was detected in graft area. Changes in renal platelet trapping correlated with response to antirejection therapy

  20. The use of indium-111-labeled platelets in the management of renal transplant patients

    International Nuclear Information System (INIS)

    Sinzin ger, H.F.; Leithner, C.W.

    1985-01-01

    The authors begin by explaining the role of pltelets in the pathogenesis of renal transplant rejection. During the sudden and severe immunilogical event that characterizes hyperacute rejection, when the endothelium is damaged, platelets accumulate on its surface. In chronic graft rejection, platelets liberate a growth factor that stimulates proliferation of arterial smooth muscle cells, and therefore might initiate and promote obliterative arteriopathy. In the opinion of these authors, platelet scanning has contributed greatly to the understanding of the role of platelets in the different kinds of graft rejection. The important remaining question is whether platelets deposit before, concomitantly with, or after infiltration by lymphocytes

  1. Early diagnosis of acute postoperative renal transplant rejection by indium-111-labeled platelet scintigraphy

    International Nuclear Information System (INIS)

    Tisdale, P.L.; Collier, B.D.; Kauffman, H.M.

    1986-01-01

    A prospective evaluation of 111 In-labeled platelet scintigraphy (IPS) for the early diagnosis of acute postoperative renal transplant rejection (TR) was undertaken. The results of IPS were compared with in vitro biochemical tests, the clinical finding of graft tenderness, and combined [/sup 99m/Tc]DTPA and [ 131 I]orthoiodohippurate scintigraphy. With a sensitivity of 0.93 and a specificity of 0.95, IPS provided otherwise unavailable diagnostic information. Furthermore, postoperative IPS was a good predictor of long-term allograft survival

  2. Detection of rejection of canine orthotopic cardiac allografts with indium-111 lymphocytes and gamma scintigraphy

    International Nuclear Information System (INIS)

    Eisen, H.J.; Rosenbloom, M.; Laschinger, J.C.; Saffitz, J.E.; Cox, J.L.; Sobel, B.E.; Bolman, R.M. III; Bergmann, S.R.

    1988-01-01

    Previous studies have demonstrated the feasibility of detecting canine heterotopic cardiac allograft rejection scintigraphically after administration of 111In lymphocytes. To determine whether the approach is capable of detecting rejection in orthotopic cardiac transplants in which labeled lymphocytes circulating in the blood pool may reduce sensitivity, the present study was performed in which canine orthotopic cardiac transplants were evaluated in vivo. Immunosuppression was maintained with cyclosporine A (10-20 mg/kg/day) and prednisone (1 mg/kg/day) for 2 wk after transplantation. Subsequently, therapy was tapered. Five successful allografts were evaluated scintigraphically every 3 days after administration of 100-350 microCi 111In autologous lymphocytes. Correction for labeled lymphocytes circulating in the blood pool, but not actively sequestered in the allografts was accomplished by administering 3-6 mCi 99mTc autologous erythrocytes and employing a previously validated blood-pool activity correction technique. Cardiac infiltration of labeled lymphocytes was quantified as percent indium excess (%IE), scintigraphically detectable 111In in the transplant compared with that in blood, and results were compared with those of concomitantly performed endomyocardial biopsy. Scintigraphic %IE for hearts not undergoing rejection manifest histologically was 0.7 +/- 0.4. Percent IE for rejecting hearts was 6.8 +/- 4.0 (p less than 0.05). Scintigraphy detected each episode of rejection detected by biopsy. Scintigraphic criteria for rejection (%IE greater than 2 s.d. above normal) were not manifest in any study in which biopsies did not show rejection. Since scintigraphic results with 111In-labeled lymphocytes were concordant with biopsy results in orthotopic cardiac transplants, noninvasive detection of graft rejection in patients should be attainable with the approach developed

  3. Indium-111 platelet imaging for detection of platelet deposition in abdominal aneurysms and prosthetic arterial grafts

    International Nuclear Information System (INIS)

    Ritchie, J.L.; Stratton, J.R.; Thiele, B.; Haminton, G.W.; Warrick, L.N.; Huang, T.W.; Harker, L.A.

    1981-01-01

    Thirty-four platelet imaging studies were performed in 23 patients to determine whether platelet deposition could be detected in patients with vascular aneurysms (18 patients) or in patients in whom Dacron prosthetic grafts had been placed (5 patients). In patients in whom abnormal platelet deposition was detected, the effect of administration of platelet-active drugs on platelet deposition was examined. Of the 18 patients with an aneurysm, 12 had equivocally positive studies on initial imaging and 2 had equivocally positive images. Of five patients with Dacron arterial grafts in place, four had diffuse platelet deposition in the grafts; the fifth patient had a platelet deposition only in a pseudoaneurysm. Eight patients with an abdominal aneurysm and positive or equivocally positive baseline images were restudied during platelet-active drug therapy either with aspirin plus dipyridamole (seven patients) or with sulfinpyrazone (four patients). No patient studied during treatment with aspirin plus dipyridamole had detectably decreased platelet deposition compared with baseline determinations. In contrast, two of four patients studied while receiving sulfinpyrazone showed decreased platelet deposition. Thus, platelet imaging may be of value for studying platelet physiology in vivo and for assessing platelet-active drugs and the thrombogenicity of prosthetic graft materials in human beings

  4. Preparation of a viable population of indium-111-labelled human blood platelets

    International Nuclear Information System (INIS)

    Heyns, A.; Badenhorst, P.N.; Pieters, H.; Loetter, M.G.; Minnaar, P.C.; Duyvene de Wit, L.J.; Reenen, O.R. van; Retief, F.P.; University of the Orange Free State, Bloemfontein; University of the Orange Free State, Bloemfontein; University of the Orange Free State, Bloemfontein

    1980-01-01

    Factors influencing labelling of human platelets with 111 Indium-8-hydroxyquinoline ([ 111 In]-oxine) in a physiological saline medium were investigated. The efficiency of labelling is influenced by time of incubation, concentration of oxine, and pH of the incubating medium. It was found that a viable platelet population could be labelled under the following conditions: (1) centrifugation of platelet rich plasma in polystyrene conical tubes at 800 g for 15 min; (2) resuspension of the platelet pellet in saline, pH 5.5; (3) incubating for 30 min at 22 0 C with [ 111 In]-oxine at a concentration of 6.25 mg oxine/litre platelet suspension; (4) washing once with platelet poor autologous plasma (PPP); and (5) finally suspending the platelets in PPP. The labelled platelets aggregated normally with collagen and ADP. Electron microscopy, done immediately after labelling, showed internal organelle reorganization characteristic of activated platelets. These ultrastructural features were reversible on incubationin PPP at 37 0 C for 30 min. The 111 In is not released from aggregated platelets and the label does not elute from incubated platelets for at least five hr. We conclude that human platelets thus labelled are suitable for in vivo kinetic studies. (orig.) [de

  5. In vitro effects on Indium-111-Oxine labeled leukocytes functions of N-etilmycin

    International Nuclear Information System (INIS)

    Iacovo, R.D.; Perna, M.; Esposito, G.; Polese, C.; Frizzi, L.

    1985-01-01

    In order to study in vitro chemotaxis, phagocytosis and bactericydal efficiencies of granulocytes (PMN) and monocytes (Mo) of cancer patients with solid tumours, the authors have undertaken the evaluation of a method of measuring PMN and Mo chemotaxis with modified Boyden chambers, using In-111-oxine. The tests were performed in order to evaluate the interference of N-etilmycin with leukocyte functions, a currently fashionable antibiotic used in the treatment of gram-negative infections. The results both compare well with the visual method and are objective. Cancer patients, disease-free for a minimum of one year, were compared and evidenced normal chemotaxis and normal controls. No difference between the two groups was found (20.46% of those tested). The addition of N-etilmy-cin (6μg/ml) to PMN and Mo further decreased the chemotaxis from 20.46% to 16.07% (t=2.81, P=0.0102). The addition of 30μg/ml further decreased the chemotaxis from the mean control values to 5.925% (t=4.55,P 1%). The use of N-etilmycin in disease-free cancer patients should be avoided in the possible event of tumour enhancement

  6. Homing pattern of indium-111 T-lymphocytes in normal and tumor bearing rats

    International Nuclear Information System (INIS)

    Kasi, L.P.; Glenn, H.J.; Mehta, K.; Teckemeyer, I.C.; Wong, W.; Haynie, T.P.

    1985-01-01

    T-lymphocytes play an important role in tumor immunology and possess cytotoxic capabilities. Purified T-lymphocytes were obtained by incubating mononuclear cells separated from peripheral blood of Fisher 344 rats in a nylon wool column at 37 0 C. The non-adherent T-lymphocytes which were eluted from the column had > 95% viability. About 1 x 10/sup 7/ purified T-lymphocytes were labeled with 30 μCi In-111 oxine (Labeling yield: 75 +-5%, viability >95%). The function of the labeled cells as estimated by their graft versus host reaction ability remained unaltered. To evaluate the distribution pattern, 1 x 10/sup 6/ In-111 T-lymphocytes (per 100g wt) were injected via tail vein in normal and in transplanted (right flank) solid hepatoma bearing Fisher 344 rats, and the percent uptake of activity of the total injected dose per organ and per gm tissue was estimated at 2, 24 and 48 hours post injection. In normal rats maximum uptakes were in the liver (24%-33%) with increasing uptakes in the spleen (6.8%-11%) and minimum uptakes in the kidneys, lungs, muscles, and blood from 2 to 48 hours after injection. The uptake pattern in tumor bearing rats were significantly different during the same time period: lower in the liver (17%-19%) and a decrease in the spleen (9%-0.4%). All other tissues displayed similar uptake patterns as in normal animals. Maximum tumor:muscle ratio (18.4) was found at 48 hours post injection. Further studies are indicated for the possible use of In-111 T-lymphocytes in T-lymphocyte disorders, inflammations, and as an additional tool in the diagnosis of tumors

  7. Value of Indium-111m labeled platelet scans for predicting early renal allograft loss

    International Nuclear Information System (INIS)

    Shaffer, P.; Hinkle, G.; Olsen, J.; Sommer, B.; Henry, M.; Ferguson, R.

    1985-01-01

    In order to determine if In-111m labeled platelet scanning could be of use in predicting renal allograft prognosis, 41 patients (pts) thought to be at risk for graft loss were studied. In vitro labeling of platelets was performed followed by reinjection into the pt and scanning at 24 hours. The graft activity on platelet scan was compared to hepatic activity and classified as being either less than or equal to hepatic activity (NEG) or much greater than hepatic activity (POS). Results are compared to graft prognosis and are presented in this paper. The observed increase in early loss rate in the pts with POS scan over those with NEG scan was highly significant. (p .001). All pts with a POS scan were on cyclosporin A (CYA); no pt on conventional therapy (excluding CYA) had a POS scan. The authors conclude that the presence of a POS scan is a grave prognostic sign and that there appears to be a relationship between CYA, POS scan, and early graft loss

  8. Value of blood-pool subtraction in cardiac indium-111-labeled platelet imaging

    Energy Technology Data Exchange (ETDEWEB)

    Machac, J.; Vallabhajosula, S.; Goldman, M.E.; Goldsmith, S.J.; Palestro, C.; Strashun, A.; Vaquer, R.; Phillips, R.A.; Fuster, V. (Mt. Sinai Medical Center, New York, NY (USA))

    1989-09-01

    Blood-pool subtraction has been proposed to enhance {sup 111}In-labeled platelet imaging of intracardiac thrombi. We tested the accuracy of labeled platelet imaging, with and without blood-pool subtraction, in ten subjects with cardiac thrombi of varying age, eight with endocarditis being treated with antimicrobial therapy and ten normal controls. Imaging was performed early after labeled platelet injection (24 hr or less) and late (48 hr or more). Blood-pool subtraction was carried out. All images were graded subjectively by four experienced, blinded readers. Detection accuracy was measured by the sensitivity at three fixed levels of specificity estimated from receiver operator characteristic curve analysis and tested by three-way analysis of variance. Detection accuracy was generally improved on delayed images. Blood-pool subtraction did not improve accuracy. Although blood-pool subtraction increased detection sensitivity, this was offset by decreased specificity. For this population studied, blood-pool subtraction did not improve subjective detection of abnormal platelet deposition by 111In platelet imaging.

  9. False-positive indium-111 labeled leukocyte scintigram in a patient with a painful hip prosthesis

    International Nuclear Information System (INIS)

    Feldman, N.; Makler, P.T. Jr.; Alavi, A.

    1986-01-01

    A Tronzo hip prosthesis is designed to elicit an inflammatory reaction in order to promote prosthesis stability. A three-phased bone scan and Ga-67 imaging in conjunction with physical examination and laboratory findings failed to demonstrate evidence for osteomyelitis in a patient with a painful hip prosthesis, in whom images obtained with In-111-labeled leukocytes were positive. This observation demonstrated that the interpretation of the latter technique in demonstrating inflammation can cause a false impression of an infectious process

  10. Functional alterations of human platelets following indium-111 labelling using different incubation media and labelling agents

    International Nuclear Information System (INIS)

    Isaka, Yoshinari; Imaizumi, Masatoshi; Kimura, Kazufumi; Matsumoto, Masayasu; Kamada, Takenobu

    1991-01-01

    Human platelets were labelled in the absence of presence of plasma using 111 In-labelled oxine sulphate, tropolone or 2-mercaptopyridine-N-oxide (MPO). Under in vitro and in vivo conditions, platelet functions were evaluated by measuring their aggregability, survival, recovery and early distribution. High labelling efficiency was achieved in saline labelling, whereas with plasma labelling, it was necessary to concentrate the platelet-rich plasma to 4.8x10 6 platelets/μl. The aggregation of platelets labelled in plasma or saline was compared with that of controls; platelets labelled in saline showed lower aggregability in 2 μM ADP but not in 5 μM ADP nor with collagen. No significant differences in platelet survival and recovery were noted between platelets labelled in plasma and those labelled in saline. Our results indicate that partial loss of ADP aggregability in vitro does not influence the in vivo viability of platelets labelled in saline. Scintigraphic studies showed that platelets labelled in a saline medium were temporarily sequestrated in the liver but not in the spleen or heart. Thus, platelet labelling in saline does not affect platelet function adversely, but platelets labelled in plasma are more desirable for assessing the early distribution of platelets in the reticuloendothelial system. (orig.)

  11. The use of indium-111 oxine platelet scintigraphy and survival studies in pediatric patients with thrombocytopenia

    International Nuclear Information System (INIS)

    Castle, V.P.; Shulkin, B.L.; Coates, G.; Andrew, M.

    1989-01-01

    We have utilized 111 In-labeled heterologous platelets to investigate the mechanism of thrombocytopenia in ten children. From the scintigraphic findings, platelet survival times, and clinical information, thrombocytopenia was ascribed to decreased production or to increased destruction. Two patients were found to have bone marrow production defects. Two patients with hemangiomas were studied. In one, the hemangioma was shown not to be the cause of thrombocytopenia. In the second, the hemangioma was proven the source of platelet destruction, but was much more extensive than clinically evident. In both, surgical manipulation of the hemangioma was avoided. Six additional patients had thrombocytopenia due to accelerated destruction. In four, the spleen was shown responsible. In two, however, the spleen was shown not to be responsible for the low platelet counts, and splenectomy was avoided. Thus, 111 In-platelet scintigraphy and survival studies are valuable in the classification and management of childhood thrombocytopenia. We believe that this study should be performed, when possible, in any child with thrombocytopenia where the mechanism is unclear or the therapeutic intervention involves splenectomy or resection of a hemangioma

  12. Indium-111 leukocyte scintigraphic detection of myocardial abscess formation in patients with endocarditis

    International Nuclear Information System (INIS)

    Cerqueira, M.D.; Jacobson, A.F.

    1989-01-01

    Myocardial abscess formation in patients with bacterial endocarditis in most clinical settings, especially in patients with prosthetic valves, is a primary indicator for surgical valve replacement. We report the detection of myocardial abscesses using 111 In leukocyte scintigraphy in three patients with prosthetic or native valve endocarditis and nondiagnostic echocardiograms. Leukocyte scintigraphy may allow identification of myocardial abscess formation earlier than other imaging modalities

  13. Indium-111-oxine labeled platelet scintigraphy for detection of intracardiac and intravascular thrombi

    Energy Technology Data Exchange (ETDEWEB)

    Kimura, Michio; Ojima, Kenji; Tsuda, Takashi [Niigata Univ. (Japan). School of Medicine

    1983-09-01

    This study was designed to evaluate the efficacy of scintigraphy by using /sup 111/In-oxine labeled platelets for the detection of either intracardiac or intravascular thrombi. Fourteen cases of thrombi diagnosed or suspected on the basis of either angiography or two-dimensional echography were examined. They included four cases of left ventricular thrombi, three of left atrial thrombi, four of vascular thrombi and three of inflammatory disease. Platelet samples from the patients were labeled by /sup 111/In-oxine according to the method originated by Yui et al. The labeling efficiency was 72.4+-9.8%. The platelets retained good function except for collagen aggregability. Hot areas of high quality in the scintigram were demonstrated in six cases including two with left ventricular thrombi, two with left atrial thrombi and two with vascular thrombi. These areas accorded well with the findings of angiography, echography or surgery. The removed thrombi had a layer of aggregated platelets on the surface. Platelet survival was shortened in a case of prosthetic valve endocarditis without a hot area, and was normal in four out of the five cases including two with a hot area. It is concluded that this method is potentially predictive in detecting thrombi.

  14. Value of blood-pool subtraction in cardiac indium-111-labeled platelet imaging

    International Nuclear Information System (INIS)

    Machac, J.; Vallabhajosula, S.; Goldman, M.E.; Goldsmith, S.J.; Palestro, C.; Strashun, A.; Vaquer, R.; Phillips, R.A.; Fuster, V.

    1989-01-01

    Blood-pool subtraction has been proposed to enhance 111 In-labeled platelet imaging of intracardiac thrombi. We tested the accuracy of labeled platelet imaging, with and without blood-pool subtraction, in ten subjects with cardiac thrombi of varying age, eight with endocarditis being treated with antimicrobial therapy and ten normal controls. Imaging was performed early after labeled platelet injection (24 hr or less) and late (48 hr or more). Blood-pool subtraction was carried out. All images were graded subjectively by four experienced, blinded readers. Detection accuracy was measured by the sensitivity at three fixed levels of specificity estimated from receiver operator characteristic curve analysis and tested by three-way analysis of variance. Detection accuracy was generally improved on delayed images. Blood-pool subtraction did not improve accuracy. Although blood-pool subtraction increased detection sensitivity, this was offset by decreased specificity. For this population studied, blood-pool subtraction did not improve subjective detection of abnormal platelet deposition by 111In platelet imaging

  15. Quantitation of thrombogenicity of hemodialyzer with technetium-99m and indium-111 labeled platelets

    International Nuclear Information System (INIS)

    Dewanjee, M.K.; Kapadvanjwala, Mansoor; Ruzius, Kees; Serafini, A.N.; Zilleruelo, G.E.; Sfakianakis, G.N.

    1993-01-01

    The platelet thromobogenicity of a hemodialyzer was quantified with 99m Tc- and 111 In-labeled platelets. The platelets collected from blood of Beagle dogs, Yorkshire pigs and human volunteers were labeled with 111 in-tropolone (detergent-free) and 99m Tc-HMPAO. Hemodialysis was performed with a hollow-fiber dialyzer (HFD) in a flow-loop, the temperature of which was maintained at 37 o C, with flow-rates of 7, 150 and 270 mL/min; after dialysis, the HFD radioactivity was measured with an ionization chamber and imaged with a γ-camera. The radioactivity of samples of hollow-fibers taken from the top, middle and bottom of the dialyzer was determined with a γ-counter. The mean values of hemodialyzer-adherent platelet radioactivity were calculated for both radionuclides. The canine platelets were found to be more thrombogenic than porcine and human platelets. The adhesivity of porcine platelets to the biomaterial (cellulose-acetate) of the dialyzer approximated that of human platelets. The 99m Tc label underestimated the thrombus formation (P 111 In- and 99m Tc-labeled platelets suggests that both radionuclides could be used for measurement of device-induced thrombogenicity and may provide an estimation of prosthesis-induced thrombogenicity of human platelets from animal studies. (Author)

  16. Quantitation of thrombogenicity of hemodialyzer with technetium-99m and indium-111 labeled platelets

    Energy Technology Data Exchange (ETDEWEB)

    Dewanjee, M.K.; Kapadvanjwala, Mansoor; Ruzius, Kees; Serafini, A.N.; Zilleruelo, G.E.; Sfakianakis, G.N. (Miami Univ., FL (United States). School of Medicine Althin CD-Medical Inc., Miami Lakes, FL (United States))

    1993-07-01

    The platelet thromobogenicity of a hemodialyzer was quantified with [sup 99m]Tc- and [sup 111]In-labeled platelets. The platelets collected from blood of Beagle dogs, Yorkshire pigs and human volunteers were labeled with [sup 111]in-tropolone (detergent-free) and [sup 99m]Tc-HMPAO. Hemodialysis was performed with a hollow-fiber dialyzer (HFD) in a flow-loop, the temperature of which was maintained at 37[sup o]C, with flow-rates of 7, 150 and 270 mL/min; after dialysis, the HFD radioactivity was measured with an ionization chamber and imaged with a [gamma]-camera. The radioactivity of samples of hollow-fibers taken from the top, middle and bottom of the dialyzer was determined with a [gamma]-counter. The mean values of hemodialyzer-adherent platelet radioactivity were calculated for both radionuclides. The canine platelets were found to be more thrombogenic than porcine and human platelets. The adhesivity of porcine platelets to the biomaterial (cellulose-acetate) of the dialyzer approximated that of human platelets. The [sup 99m]Tc label underestimated the thrombus formation (P < 0.01 ). The dynamic processes of thrombosis and embolization from the hemodialyzer resulted in the large standard deviations around the mean values of the adherent thrombus. In spite of this limitation of the dynamic pathology, the quantitation of comparative throbogenicity with [sup 111]In- and [sup 99m]Tc-labeled platelets suggests that both radionuclides could be used for measurement of device-induced thrombogenicity and may provide an estimation of prosthesis-induced thrombogenicity of human platelets from animal studies. (Author).

  17. Quantitation of thrombogenicity of hemodialyzer with technetium-99m and indium-111 labeled platelets

    International Nuclear Information System (INIS)

    Dewanjee, M.K.; Kapadvanjwala, M.; Ruzius, K.; Serafini, A.N.; Zilleruelo, G.E.; Sfakianakis, G.N.

    1993-01-01

    The platelet thrombogenicity of a hemodialyzer was quantified with 99m Tc- and 111 In-labeled platelets. The platelets collected from blood of Beagle dogs, Yorkshire pigs and humans were labeled with 111 In-tropolone (detergent-free) and 99m Tc-HMPAO. Hemodialysis was performed with a hollow-fiber dialyzer (HFD) in a flow-loop, the temperature maintained at 37 o C, with flow-rates of 7, 150 and 270 mL/min; after dialysis, HFD radioactivity was measured with an ionization chamber and imaged with a γ-camera. The dynamic processes of thrombosis and embolization from the hemodialyzer resulted in large standard deviations around the mean values of the adherent thrombus. In spite of this, the quantitation of comparative thrombogenicity with 111 In-and 99m Tc-labeled platelets suggests that both radionuclides could be used for measurement of device-induced thrombogenicity and estimation of prosthesis-induced thrombogenicity. (author)

  18. Effect of antibiotic therapy on the sensitivity of indium-111-labeled leukocyte scans

    International Nuclear Information System (INIS)

    Datz, F.L.; Thorne, D.A.

    1986-01-01

    Although 111 In-labeled leukocytes have been shown to be a useful technique for detecting infection, it has been postulated that antibiotic therapy may reduce the sensitivity of the leukocyte scan. Many patients with suspected bacterial infections are placed on antibiotics before a definite site of infection has been identified. Three hundred twelve leukocyte scans on 271 patients were retrospectively reviewed and classified as positive or negative, and as to whether or not they were being treated with antibiotics at the time the leukocyte scan was performed. The overall sensitivity, considering all 312 studies, was 90%. One hundred sixty-nine patient studies were on patients receiving antibiotics; 143 studies were on patients not on antibiotics. The sensitivity of the leukocyte scan was 88.7% in patients on antibiotic therapy; it was 92.1% in those who were not receiving antibiotics. The differences in sensitivity between the two groups were not significantly different (p less than 0.05). We conclude that antibiotic therapy does not affect the sensitivity of the 111 In-labeled leukocyte scan

  19. Monoclonal antibodies in pediatric allergy

    Directory of Open Access Journals (Sweden)

    Amelia Licari

    2015-10-01

    Full Text Available Production of monoclonal antibodies (mAbs involving human-mouse hybrid cells was first described in 1970s, but these biologics are now used for a variety of diseases including cancers, autoimmune disorders and allergic diseases. The aim of this article is to review current and future applications of mAbs, in particular focusing on anti-IgE therapy, in the field of pediatric allergy. Proceedings of the 11th International Workshop on Neonatology and Satellite Meetings · Cagliari (Italy · October 26th-31st, 2015 · From the womb to the adultGuest Editors: Vassilios Fanos (Cagliari, Italy, Michele Mussap (Genoa, Italy, Antonio Del Vecchio (Bari, Italy, Bo Sun (Shanghai, China, Dorret I. Boomsma (Amsterdam, the Netherlands, Gavino Faa (Cagliari, Italy, Antonio Giordano (Philadelphia, USA

  20. Monoclonal gammopathy in rheumatic diseases.

    Science.gov (United States)

    Yang, Yue; Chen, Long; Jia, Yuan; Liu, Yang; Wen, Lei; Liang, Yaoxian; An, Yuan; Chen, Shi; Su, Yin; Li, Zhanguo

    2018-07-01

    To analyze the clinical spectrum, laboratory characteristics, and outcomes of monoclonal gammopathy (MG) in patients with rheumatic diseases. Screening for the presence of MG was performed in 872 inpatients with rheumatic diseases from January 2010 to July 2017. A total of 41 patients were enrolled. Their clinical and biological features in addition to outcomes were described. For each patient with primary Sjögren syndrome (pSS), 2 age- and sex-matched pSS patients without MG were selected as controls. Risk factors for the presence of MG and malignant hematological neoplasias were assessed. MG was observed in patients with SS, rheumatoid arthritis, systemic lupus erythematosus, ankylosing spondylitis, primary biliary cirrhosis, polymyositis, hypomyopathic dermatomyositis, psoriatic arthritis, ANCA-associated vasculitis, polyarteritis nodosa, and polymyalgia rheumatic, with SS the most frequent type. Serum M protein was detected in 37 patients. The monoclonal bands identified in serum were 16 IgG (5 κ, 11 λ), 11 IgA (6 κ, 5 λ), 6 IgM (5 κ, 1 λ), and 4 free λ chains. M components were observed in urine in the other 4 patients. High ESR, albumin/globulin inversion, rheumatoid factor positivity, hypergammaglobulinemia, and hypocomplementemia were common features, presented in more than half of the 41 patients. Patients with pSS, when complicated with MG, showed a higher rate of abnormal urine NAG (71.4 vs 15.8%, P = 0.025), higher levels of ESR [55.0 (53.5) mm/h vs 21.0 (31.8) mm/h, P = 0.001], ESSDAI [26.0 (25.0) vs 12.0 (9.0), P = 0.006], and ClinESSDAI scores [24.0 (25.0) vs 10.5 (10.0), P = 0.011]. Multivariate analysis revealed that the disease activity, assessed by either ESSDAI [adjusted OR 1.127 (95%CI 1.015-1.251), P = 0.025] or ClinESSDAI [adjusted OR 1.121 (95%CI 1.011-1.242), P = 0.030], was the only independent risk factor for the presence of MG. During the follow-up, 2 patients had transient serum M protein, 2 had isotype

  1. Relationship between hyperthyroidism and monoclonal gammapathy

    International Nuclear Information System (INIS)

    Canas, Carlos Alberto

    2007-01-01

    A 66-year-old man with primary hyperparathyroidism (PHPT) and monoclonal gammapathy associated to it of uncertain significance (MGUS). A possible pathogenic relationship between HPTP and MGUS is analyzed. Interleukin 6 could play a pivotal role.

  2. Monoclonal antibody therapy of inflammatory bowel disease

    NARCIS (Netherlands)

    van Deventer, S. J.; Camoglio, L.

    1997-01-01

    Animal models of inflammatory bowel disease have provided insight in the regulation of mucosal inflammation. This has resulted in novel therapeutic approaches that specifically target a single inflammatory mediator. Monoclonal antibody therapy has been used in steroid refractory Crohn's disease

  3. Monoclonal for cancer detection and therapy

    International Nuclear Information System (INIS)

    Baldwin, R.W.; Byers, V.S.

    1985-01-01

    This book contains 18 chapters. Some of the chapter titles are: Monoclonal Antibodies to Breast Cancer and Their Application; Clinical Applications of Radioimmunolocalisation; Localisation of Cancer of the Ovary and Metastases Using 123 I-labelled Monoclonal Antibody HMFG-2 Compared to Surgical Findings; Interest of Globotriaosylceramide Membrane Antigen as Target for Immunotoxins; and Analysis, Results and Future Prospective of the Therapeutic Use of Radiolabeled Antibody in Cancer Therapy

  4. Antibodies and Selection of Monoclonal Antibodies.

    Science.gov (United States)

    Hanack, Katja; Messerschmidt, Katrin; Listek, Martin

    Monoclonal antibodies are universal binding molecules with a high specificity for their target and are indispensable tools in research, diagnostics and therapy. The biotechnological generation of monoclonal antibodies was enabled by the hybridoma technology published in 1975 by Köhler and Milstein. Today monoclonal antibodies are used in a variety of applications as flow cytometry, magnetic cell sorting, immunoassays or therapeutic approaches. First step of the generation process is the immunization of the organism with appropriate antigen. After a positive immune response the spleen cells are isolated and fused with myeloma cells in order to generate stable, long-living antibody-producing cell lines - hybridoma cells. In the subsequent identification step the culture supernatants of all hybridoma cells are screened weekly for the production of the antibody of interest. Hybridoma cells producing the antibody of interest are cloned by limited dilution till a monoclonal hybridoma is found. This is a very time-consuming and laborious process and therefore different selection strategies were developed since 1975 in order to facilitate the generation of monoclonal antibodies. Apart from common automation of pipetting processes and ELISA testing there are some promising approaches to select the right monoclonal antibody very early in the process to reduce time and effort of the generation. In this chapter different selection strategies for antibody-producing hybridoma cells are presented and analysed regarding to their benefits compared to conventional limited dilution technology.

  5. Systemic radiotherapy with monoclonal antibodies

    International Nuclear Information System (INIS)

    Sautter-Bihl, M.L.; Matzku, S.; Bihl, H.

    1993-01-01

    In this experimental study, feasibility and efficiency of systematic radiotherapy with the I-131 labelled monoclonal antibody BW575/9 (radioimmunotherapy) are investigated using human SK-N-SH neuroblastoma transplated into nude mice. Series of six nude mice were treated with intravenous application of 400 μCi (group 1), 700 μCi (group 2) of the I-131 labelled and of the unlabelled MAb (group 3). An untreated group (group 4) served as control. Tumors of group (3) and (4) showed an identical growth. In group (1), tumor growth was arrested for seven days. In group (2), the tumor showed complete regression after eight days which lasted for 55 days. Thereafter, the tumor started to regrow. This growth characteristics are correlated with the doses achieved in the tumor using a medical radiation dose (MIRD) formulation. The biodistribution data necessary for MIRD calculation were obtained by previously performed experiments with the I-125 labelled MAb. The doses assessed in the tumor turned out to be five to ten times greater than those in normal tissues (liver, bone, etc.) These results confirm feasibility, selectivity and efficiency of radioimmunotherapy in the above described model. Moreover, this in vivo model seems suitable for further investigations concerning fundamental issues of radioimunotherapy. (orig.) [de

  6. Monoclonal antibodies in oncology. Review article

    Energy Technology Data Exchange (ETDEWEB)

    Chan, S Y.T.; Sikora, K

    1986-05-01

    Monoclonal antibodies (MCAs) can be used to differentiate between normal and neoplastic cells and thus exploited for diagnostic and, ultimately, therapeutic gain. The evidence for the existence of human tumour antigens is reviewed. Several areas of diagnosis are already benefiting from the application of the monoclonal technology. Immunohistology can help the pathologist with difficult diagnostic problems. New classifications of lymphoma and leukaemia can be based on specific surface molecules. Similarly, the detection of shed tumour antigens is already established as part of the routine assessment of many patients with common solid tumours. Isotopically labeled monoclonal antibodies have been used to localise primary and metastatic tumours. The use of antibodies in this way is not only a promising diagnostic tool but also the first step in studying the possibility of arming antibodies to provide therapeutic agents. Such trials are currently in progress. 69 refs.; 7 figs.; 3 tabs.

  7. Tumor detection using radiolabeled monoclonal antibodies

    International Nuclear Information System (INIS)

    Moldofsky, P.J.; Powe, J.; Hammond, N.D.

    1987-01-01

    Radioisotope conjugated to monoclonal antibody products has been used for imaging tumors targeted by the antibody. As imaging progresses, new sets of procedural and technical questions arise. In this chapter, we discuss several current problems in imaging tumor with radiolabeled monoclonal antibody. These include (1) methods for selection of specific antibody and, once the particular antibody is selected, which fragment form is to be used; (2) imaging procedures: what are the optimum imaging parameters, such as optimum time for imaging after administration of tracer and considerations regarding background subtraction; and (3) noninvasive quantitative techniques: quantitation of localization of antibody indirectly from quantitative information in the images.100 references

  8. Generation of a Monoclonal Antibody against Mycoplasma spp. following Accidental Contamination during Production of a Monoclonal Antibody against Lawsonia intracellularis

    OpenAIRE

    Hwang, Jeong-Min; Lee, Ji-Hye; Yeh, Jung-Yong

    2012-01-01

    This report describes Mycoplasma contamination of Lawsonia intracellularis cultures that led to the unintended acquisition of a monoclonal antibody against Mycoplasma spp. during the attempted generation of a monoclonal antibody against L. intracellularis.

  9. Strain differentiation of polioviruses with monoclonal antibodies.

    NARCIS (Netherlands)

    A.D.M.E. Osterhaus (Albert); A.L. van Wezel; A.J.H. Stegmann; J.A.A.M. van Asten (Jack)

    1984-01-01

    textabstractPanels of monoclonal antibodies raised against different poliovirus type 1, 2 and 3 strains, were tested in a micro-neutralization test and in a micro-enzyme linked immunosorbent assay against a large number of poliovirus strains. The results were compared with those obtained with the

  10. Monoclonal antibodies reactive with hairy cell leukemia

    NARCIS (Netherlands)

    Visser, L; Shaw, A; Slupsky, J; Vos, H; Poppema, S

    Monoclonal antibodies reactive with hairy cell leukemia were developed to aid in the diagnosis of this subtype of B cell chronic lymphocytic leukemia and to gain better insight into the origin of hairy cells. Three antibodies were found to be of value in the diagnosis of hairy cell leukemia.

  11. Monoclonal antibody technologies and rapid detection assays

    Science.gov (United States)

    Novel methodologies and screening strategies will be outlined on the use of hybridoma technology for the selection of antigen specific monoclonal antibodies. The development of immunoassays used for diagnostic detection of prions and bacterial toxins will be discussed and examples provided demonstr...

  12. Monoclonal antibody therapy of inflammatory bowel disease

    NARCIS (Netherlands)

    van Deventer, S. J.; Camoglio, L.

    1996-01-01

    Several anti-inflammatory drugs have therapeutic efficacy in inflammatory bowel disease, but their targets remain incompletely characterized. The development of monoclonal antibodies that either recognize epitopes on immune-competent cells, or neutralize pro-inflammatory cytokines, has helped to

  13. Monoclonal Antibody Therapy for Advanced Neuroblastoma

    Science.gov (United States)

    NCI is sponsoring two clinical trials of a monoclonal antibody called ch14.18, in combination with other drugs, to see if the antibody may be helpful for children or young adults (up to age 21) with relapsed or refractory neuroblastoma.

  14. Recent developments in monoclonal antibody radiolabeling techniques

    Energy Technology Data Exchange (ETDEWEB)

    Srivastava, S.C.; Mease, R.C.

    1989-01-01

    Monoclonal antibodies (MAbs) have shown the potential to serve as selective carriers of radionuclides to specific in vivo antigens. Accordingly, there has been an intense surge of research activity in an effort to develop and evaluate MAb-based radiopharmaceuticals for tumor imaging (radioimmunoscintigraphy) and therapy (radioimmunotherapy), as well as for diagnosing nonmalignant diseases. A number of problems have recently been identified, related to the MAbs themselves and to radiolabeling techniques, that comprise both the selectivity and the specificity of the in vivo distribution of radiolabeled MAbs. This paper will address some of these issues and primarily discuss recent developments in the techniques for radiolabeling monoclonal antibodies that may help resolve problems related to the poor in vivo stability of the radiolabel and may thus produce improved biodistribution. Even though many issues are identical with therapeutic radionuclides, the discussion will focus mainly on radioimmunoscintigraphic labels. 78 refs., 6 tabs.

  15. Quantitative imaging with radiolabeled monoclonal antibodies

    International Nuclear Information System (INIS)

    Moldofsky, P.J.; Hammond, N.D.

    1988-01-01

    The ability to image tumor by using radiolabeled monoclonal antibody products has been widely demonstrated. The questions of safety and efficacy remain open and require further experience, but at least in some clinical situations radioimmunoimaging has provided clinically useful information. Imaging tumor with radiolabeled monoclonal and polyclonal antibodies has been widely reported, and several summaries have recently appeared. For extensive review of recent clinical imaging the reader is referred to these excellent sources. Having demonstrated the possibility of imaging tumor with radiolabeled antibody, the question now apparent is: will the imaging modality provide information new and different from the already available with established techniques in computed tomography, magnetic resonance imaging, and standard nuclear medicine?

  16. [Monoclonal antibodies in diagnosis of acute leukemias].

    Science.gov (United States)

    Krawczyńska, A; Robak, T

    1996-01-01

    Immunophenotyping has become an essential component for the study of acute myeloblastic (AML) and lymphoblastic (ALL) leukaemias. The recent development of highly specific monoclonal antibodies (Mc Ab) to differentiation antigens (CD) of haematopoetic cells have made it readily available to clinical laboratories in most major hospitals. Immunophenotyping complements standard morphology by providing information on lineage, stage of differentiation and clonality. In addition some of the flow cytometry findings have independent prognostic significance. Monoclonal antibodies useful in defining lineage (B-cell versus T-cell) and stages of differentiation of ALL. It can be also used in identifying characteristic feature of AML and aiding in lineage determination in acute leukaemias that are morphologically undifferentiated. Surface immunophenotyping is especially helpful for recognizing mixed lineage acute leukaemia and diagnosing certain rare entities such as erythroleukaemia (M6), acute megakaryocytic leukaemia (M7) and minimally differentiation acute myeloid leukaemia.

  17. Recent developments in monoclonal antibody radiolabeling techniques

    International Nuclear Information System (INIS)

    Srivastava, S.C.; Mease, R.C.

    1989-01-01

    Monoclonal antibodies (MAbs) have shown the potential to serve as selective carriers of radionuclides to specific in vivo antigens. Accordingly, there has been an intense surge of research activity in an effort to develop and evaluate MAb-based radiopharmaceuticals for tumor imaging (radioimmunoscintigraphy) and therapy (radioimmunotherapy), as well as for diagnosing nonmalignant diseases. A number of problems have recently been identified, related to the MAbs themselves and to radiolabeling techniques, that comprise both the selectivity and the specificity of the in vivo distribution of radiolabeled MAbs. This paper will address some of these issues and primarily discuss recent developments in the techniques for radiolabeling monoclonal antibodies that may help resolve problems related to the poor in vivo stability of the radiolabel and may thus produce improved biodistribution. Even though many issues are identical with therapeutic radionuclides, the discussion will focus mainly on radioimmunoscintigraphic labels. 78 refs., 6 tabs

  18. Taking aim at cancer with monoclonal antibodies

    International Nuclear Information System (INIS)

    Klausner, A.

    1986-01-01

    Conjugating radioisotopes to monoclonal antibodies could have certain advantages in cancer therapy. Radioactive compounds have the double-edged ability to kill cells that are up to centimeter or more away. This is a plausible way to overcome tumor heterogeneity, but it also means that normal cells near the tumor could be affected. Hybritech (San Diego, CA) has been supplying antibody linked to the radioisotope yttrium-90 for a number of clinical trials. Work at Johns Hopkins University (Baltimore, MD) has focused on polyclonal antibodies to hepatoma. Monoclonal antibodies will be used there soon, and trials could be expanded eventually to include breast, lung, and prostate cancer as well. Hybritech also expects that the yttrium-antibody conjugates developed with NCI will enter the clinic later this year for treating leukemia and lymphoma systems; treatments for melanomas should follow

  19. Monoclonal TCR-redirected tumor cell killing.

    Science.gov (United States)

    Liddy, Nathaniel; Bossi, Giovanna; Adams, Katherine J; Lissina, Anna; Mahon, Tara M; Hassan, Namir J; Gavarret, Jessie; Bianchi, Frayne C; Pumphrey, Nicholas J; Ladell, Kristin; Gostick, Emma; Sewell, Andrew K; Lissin, Nikolai M; Harwood, Naomi E; Molloy, Peter E; Li, Yi; Cameron, Brian J; Sami, Malkit; Baston, Emma E; Todorov, Penio T; Paston, Samantha J; Dennis, Rebecca E; Harper, Jane V; Dunn, Steve M; Ashfield, Rebecca; Johnson, Andy; McGrath, Yvonne; Plesa, Gabriela; June, Carl H; Kalos, Michael; Price, David A; Vuidepot, Annelise; Williams, Daniel D; Sutton, Deborah H; Jakobsen, Bent K

    2012-06-01

    T cell immunity can potentially eradicate malignant cells and lead to clinical remission in a minority of patients with cancer. In the majority of these individuals, however, there is a failure of the specific T cell receptor (TCR)–mediated immune recognition and activation process. Here we describe the engineering and characterization of new reagents termed immune-mobilizing monoclonal TCRs against cancer (ImmTACs). Four such ImmTACs, each comprising a distinct tumor-associated epitope-specific monoclonal TCR with picomolar affinity fused to a humanized cluster of differentiation 3 (CD3)-specific single-chain antibody fragment (scFv), effectively redirected T cells to kill cancer cells expressing extremely low surface epitope densities. Furthermore, these reagents potently suppressed tumor growth in vivo. Thus, ImmTACs overcome immune tolerance to cancer and represent a new approach to tumor immunotherapy.

  20. New monoclonal antibody to human apolipoprotein J

    Czech Academy of Sciences Publication Activity Database

    Čapková, Jana; Geussová, Gizela; Pěknicová, Jana

    2002-01-01

    Roč. 2002, č. 48 (2002), s. 40-42 ISSN 0015-5500 R&D Projects: GA ČR GV524/96/K162 Grant - others:NFDK-MAOB(XE) 1985-NFDK-MAOB Institutional research plan: CEZ:AV0Z5052915 Keywords : apo J * human spermatoza * monoclonal antibody Subject RIV: EB - Genetics ; Molecular Biology Impact factor: 0.615, year: 2002

  1. Polyclonal and monoclonal antibodies in clinic.

    Science.gov (United States)

    Wootla, Bharath; Denic, Aleksandar; Rodriguez, Moses

    2014-01-01

    Immunoglobulins (Ig) or antibodies are heavy plasma proteins, with sugar chains added to amino-acid residues by N-linked glycosylation and occasionally by O-linked glycosylation. The versatility of antibodies is demonstrated by the various functions that they mediate such as neutralization, agglutination, fixation with activation of complement and activation of effector cells. Naturally occurring antibodies protect the organism against harmful pathogens, viruses and infections. In addition, almost any organic chemical induces antibody production of antibodies that would bind specifically to the chemical. These antibodies are often produced from multiple B cell clones and referred to as polyclonal antibodies. In recent years, scientists have exploited the highly evolved machinery of the immune system to produce structurally and functionally complex molecules such as antibodies from a single B clone, heralding the era of monoclonal antibodies. Most of the antibodies currently in the clinic, target components of the immune system, are not curative and seek to alleviate symptoms rather than cure disease. Our group used a novel strategy to identify reparative human monoclonal antibodies distinct from conventional antibodies. In this chapter, we discuss the therapeutic relevance of both polyclonal and monoclonal antibodies in clinic.

  2. Assay for the specificity of monoclonal antibodies in crossed immunoelectrophoresis

    DEFF Research Database (Denmark)

    Skjødt, K; Schou, C; Koch, C

    1984-01-01

    A method is described based on crossed immunoelectrophoresis of a complex antigen mixture in agarose gel followed by incubation of the gel with the monoclonal antibody. The bound monoclonal antibody is detected by the use of a secondary enzyme-labelled antibody. Using this technique we have been ...... I molecules. In other experiments using the same technique we demonstrated the reaction of a monoclonal antibody specific for chicken Ig light chains. Udgivelsesdato: 1984-Aug-3...

  3. Development and Characterization of Canine Distemper Virus Monoclonal Antibodies.

    Science.gov (United States)

    Liu, Yuxiu; Hao, Liying; Li, Xiangdong; Wang, Linxiao; Zhang, Jianpo; Deng, Junhua; Tian, Kegong

    2017-06-01

    Five canine distemper virus monoclonal antibodies were developed by immunizing BALB/c mice with a traditional vaccine strain Snyder Hill. Among these monoclonal antibodies, four antibodies recognized both field and vaccine strains of canine distemper virus without neutralizing ability. One monoclonal antibody, 1A4, against hemagglutinin protein of canine distemper virus was found to react only with vaccine strain virus but not field isolates, and showed neutralizing activity to vaccine strain virus. These monoclonal antibodies could be very useful tools in the study of the pathogenesis of canine distemper virus and the development of diagnostic reagents.

  4. Nuclear oncology with monoclonal antibodies and peptides

    International Nuclear Information System (INIS)

    Hosono, Makoto

    1998-01-01

    Imaging and therapy using radiolabeled monoclonal antibodies have proved useful in many clinical studies. However, immunogenicity of mouse antibodies to human and insufficient tumor-to-normal tissue ratios remained to be solved. Chimerization and humanization by genetic engineering, and multistep targeting techniques have enabled lower immunogenicity and higher tumor-to-normal tissue contrast. Peptides like somatostatin-analogs have been reportedly useful in imaging tumors, which are either somatostatin receptor positive or negative. Elevated normal tissue accumulation of radiolabeled peptides is a drawback in aiming internal radiation therapy. (author). 51 refs

  5. Monoclonal Idiotope Vaccine against Streptococcus pneumoniae Infection

    Science.gov (United States)

    McNamara, Mary K.; Ward, Ronald E.; Kohler, Heinz

    1984-12-01

    A monoclonal anti-idiotope antibody coupled to a carrier protein was used to immunize BALB/c mice against a lethal Streptococcus pneumoniae infection. Vaccinated mice developed a high titer of antibody to phosphorylcholine, which is known to protect against infection with Streptococcus pneumoniae. Measurement of the median lethal dose of the bacteria indicated that anti-idiotope immunization significantly increased the resistance of BALB/c mice to the bacterial challenge. Antibody to an idiotope can thus be used as an antigen substitute for the induction of protective immunity.

  6. Aggregates in monoclonal antibody manufacturing processes.

    Science.gov (United States)

    Vázquez-Rey, María; Lang, Dietmar A

    2011-07-01

    Monoclonal antibodies have proved to be a highly successful class of therapeutic products. Large-scale manufacturing of pharmaceutical antibodies is a complex activity that requires considerable effort in both process and analytical development. If a therapeutic protein cannot be stabilized adequately, it will lose partially or totally its therapeutic properties or even cause immunogenic reactions thus potentially further endangering the patients' health. The phenomenon of protein aggregation is a common issue that compromises the quality, safety, and efficacy of antibodies and can happen at different steps of the manufacturing process, including fermentation, purification, final formulation, and storage. Aggregate levels in drug substance and final drug product are a key factor when assessing quality attributes of the molecule, since aggregation might impact biological activity of the biopharmaceutical. In this review it is analyzed how aggregates are formed during monoclonal antibody industrial production, why they have to be removed and the manufacturing process steps that are designed to either minimize or remove aggregates in the final product. Copyright © 2011 Wiley Periodicals, Inc.

  7. Kinetics of intralymphatically delivered monoclonal antibodies

    International Nuclear Information System (INIS)

    Wahl, R.L.; Geatti, O.; Liebert, M.; Beers, B.; Jackson, G.; Laino, L.; Kronberg, S.; Wilson, B.S.; Beierwaltes, W.H.

    1985-01-01

    Radiolabeled monoclonal antibody (MoAb) administration subcutaneously (sq), so that preferential uptake is to the lymphatics, holds significant promise for the detection of lymph node metastases. Only limited information is available about clearance rates of intralymphatically administered MoAbs. I-131 labeled intact IgG (225.28S), F(ab's)2 (225.28S) or IgM (FT162) were administered sq to anesthetized Balb/C mice. Eight mice were studied with each MoAb, 4 with a foot-pad injection, 4 with an anterior abdominal injection. Gamma camera images were collected into a computer, over the first 6 hrs after injection with the animals anesthetized and immobile. Animals were then allowed to move about freely. Additional images were then acquired out to 48 hrs. Regions of interest wre selected over the injection site and the kinetics of antibody egress determined. Clearance rates from local sq injection sites are influenced by motion and somewhat by location. The class and fragment status of the MoAb appear relatively less important in determining clearance rates from sq injections than they are in determining whole-body clearance after iv injections. Additional studies using Fab fragments and additional monoclonals will be useful in extending these observations

  8. Bone marrow dosimetry for monoclonal antibody therapy

    International Nuclear Information System (INIS)

    Bigler, R.E.; Zanzonico, P.B.; Leonard, R.

    1986-01-01

    Immunoglobulins must permeate through the basement membrane of capillaries in order to enter the extracellular space (ECS) of tissue. Since the process is quite slow, the blood plasma activity in various organs contributes considerably to the radiation dose of the dose-limiting tissues. In bone marrow the basement membrane is absent and the blood circulation is functionally open. Therefore, blood plasma and marrow ECS maintain equal concentrations of labeled immunoglobulins. A combination of factors including intravenous administration, slow absorption into most tissues, slow breakdown and elimination of labeled immunoglobulin, and rapid entry into bone marrow ECS as well as known radiosensitivity of marrow led the authors to expect this tissue would prove to be the primary tissue at risk for systemic monoclonal antibody therapy. They have developed and applied in a Phase I clinical study of 131 I labeled CEA antibody a procedure for estimation of radiation dose to red bone marrow. Serieal measurements of blood plasma and total body retention are carried out. Binding of labeled antibody to the cellular components of blood is verified to be very low. They have observed bone marrow depression at doses greater than 400 rad. If no special procedures are used to reconstitute marrow after radiation treatment, this level represents a much greater than generally recognized limitation to radiolabeled monoclonal antibody therapy. 25 references, 4 tables

  9. Emerging monoclonal antibodies against Clostridium difficile infection.

    Science.gov (United States)

    Péchiné, Séverine; Janoir, Claire; Collignon, Anne

    2017-04-01

    Clostridium difficile infections are characterized by a high recurrence rate despite antibiotic treatments and there is an urgent need to develop new treatments such as fecal transplantation and immonotherapy. Besides active immunotherapy with vaccines, passive immunotherapy has shown promise, especially with monoclonal antibodies. Areas covered: Herein, the authors review the different assays performed with monoclonal antibodies against C. difficile toxins and surface proteins to treat or prevent primary or recurrent episodes of C. difficile infection in animal models and in clinical trials as well. Notably, the authors lay emphasis on the phase III clinical trial (MODIFY II), which allowed bezlotoxumab to be approved by the Food and Drug Administration and the European Medicines Agency. They also review new strategies for producing single domain antibodies and nanobodies against C. difficile and new approaches to deliver them in the digestive tract. Expert opinion: Only two human Mabs against TcdA and TcdB have been tested alone or in combination in clinical trials. However, many animal model studies have provided rationale for the use of Mabs and nanobodies in C. difficile infection and pave the way for further clinical investigation.

  10. Crossreactivity of boar sperm monoclonal antibodies with human ...

    African Journals Online (AJOL)

    Monoclonal antibodies against the head (H mabs) and tail (Tmabs) of boar spermatozoa were produced. Spermatozoa from boar, stallion, bull, human, ram, goat and rabbit were independently incubated with the monoclonal antibodies and later stained by immunofluorescence method. There were positive reactions of the ...

  11. A monoclonal antibody that specifically recognizes m6A nucleoside

    OpenAIRE

    Espuny, Ruth; Castro, Ana; Codony, Carles; Eritja Casadellà, Ramón; Bach-Elias, Montse

    1998-01-01

    A hybridoma against the nucleoside m6A has been obtained from mouse spleen. This hybridoma was named H65 and it secretes monoclonal antibodies anti-m6A. The competition assays showed that the monoclonal antibody was highly specific for m6A nucleoside.

  12. Monoclonal antibody PAL-E specific for endothelium

    NARCIS (Netherlands)

    Schlingemann, R. O.; Dingjan, G. M.; Emeis, J. J.; Blok, J.; Warnaar, S. O.; Ruiter, D. J.

    1985-01-01

    A monoclonal antibody, PAL-E, is described that is specific for endothelial cells. The monoclonal antibody, an IgG2a, markedly stains endothelium of capillaries, medium-sized and small veins, and venules in frozen sections of human and some animal tissues tested. It reacts not at all or only weakly

  13. Treatment with anti-interferon-δ monoclonal antibodies modifies experimental autoimmune encephalomyelitis in interferon-δ receptor knockout mice

    DEFF Research Database (Denmark)

    Espejo, C.; Penkowa, Milena; Saez-Torres, I.

    2001-01-01

    Neuroinflammation, neuronal degeneration, regeneration, monoclonal antibodies, multiple schlerosis......Neuroinflammation, neuronal degeneration, regeneration, monoclonal antibodies, multiple schlerosis...

  14. Induction and characterization of monoclonal anti-idiotypic antibodies reactive with idiotopes of canine parvovirus neutralizing monoclonal antibodies.

    NARCIS (Netherlands)

    G.F. Rimmelzwaan (Guus); J. van Es (Johan); G.A. Drost; F.G.C.M. Uytdehaag (Fons); A.D.M.E. Osterhaus (Albert)

    1991-01-01

    textabstractMonoclonal anti-idiotypic (anti-Id) antibodies (Ab2) were generated against idiotypes (Id) of canine parvovirus (CPV) specific monoclonal antibodies (MoAbs). The binding of most of these anti-Id antibodies to their corresponding Id could be inhibited by antigen, thus classifying these

  15. Splenic microenvironment and self recognition as factors in allograft rejection in rats. A study using indium-111-labeled cells

    International Nuclear Information System (INIS)

    Pollak, R.; Blanchard, J.M.; Lazda, V.A.

    1986-01-01

    Splenectomy facilitates organ allograft survival in some rat strains, and in weak donor-recipient histoincompatible pairs. We have found using a heart spleen twin graft model, using ACI rats as recipients and Lewis rats as donors, that the transplanted heart will survive in most recipients after delayed host splenectomy. The presence of a viable mass of splenic tissue will allow rejection to proceed only when the transplanted spleen is of host origin, and not when it comes from the donor (i.e., when it is allogeneic). The use of 111In-labeled cells has allowed us to show that lymphocyte traffic and trapping is markedly altered in the transplanted allogeneic spleens, when compared with control transplanted syngeneic spleens. Thus, despite the presence of the splenic ''microenvironment,'' cardiac allograft rejection does not occur in the absence of syngeneic splenic tissue. We conclude that the role of the spleen in the immune response is to facilitate the recognition of self and the acquisition of alloreactivity in weak responder rat strains and donor-recipient pairs

  16. Bone marrow imaging with MR and indium-111-chloride scintigraphy in patients with myelodysplasia and aplastic anemia

    International Nuclear Information System (INIS)

    Kumar, R.; Juneja, H.S.; Sayle, B.A.; Johnson, R.F.

    1989-01-01

    This paper reports twenty-one patients with myelodysplasia and aplastic anemia studied with MR and bone marrow radionuclide imaging to determine the roles of these imaging modalities, with seven normal patients serving as controls. All patients underwent In-111 chloride bone marrow scintigraphy prior to MR imaging. MR studies of the lumbar spine were acquired at 0.6 T with a T1-weighted (500/24 [repetition time (TR) msec/echo time (TE) msec]) spin-echo technique and an inversion-recovery technique (200/26/148 [TR msec/TE msec/inversion time msec])

  17. Evaluation of indium-111-2-mercaptopyridine-N-oxide for labeling leukocytes in plasma: a kit preparation

    International Nuclear Information System (INIS)

    Thakur, M.L.; McKenney, S.L.; Park, C.H.

    1985-01-01

    Pure neutrophils, lymphocytes, and mixed leukocytes have been labeled in vitro with 111 In chelated to a nontoxic, water soluble agent 2-mercaptopyridine-N-oxide (Merc). Cells were labeled in isotonic salt-balanced medium with preformed [ 111 In]Merc, or in 0.5 ml autologous plasma by incubation with dry Merc first and then with 111 In. The latter method facilitated a kit procedure that required 2 μg dry Merc when acid citrate dextrose was used as anticoagulant or 20μg when heparin was used. Labeling efficiency was dependent on cell concentration and pH. Labeled cells accumulated avidly in experimental abscesses. In dogs, the liver uptake of labeled cells was only 18.8% compared to that of 48.5% when cells were labeled with [ 111 In] oxine

  18. Detection of diffuse glomerular lesions in rats: II. Comparison of indium-111 cationic small macromolecules with technetium-99m DTPA

    International Nuclear Information System (INIS)

    McAfee, J.G.; Thomas, F.D.; Subramanian, G.; Schneider, R.D.; Lyons, B.; Roskopf, M.; Zapf-Longo, C.; Whaley, D.

    1986-01-01

    Dextrans with average molecular weights of 5000, 10,000, and 17,500 and inulin were rendered cationic by amination with 2-bromoethylamine hydrobromide. After limited coupling with DTPA cyclic dianhydride, they were labeled with 111In. A good correlation was found between their early renal uptake quantitated by camera-computer techniques and their renal clearance from multiple plasma samples in rats with glomerular damage induced by puromycin aminonucleoside and controls. However, there was poor correlation between the early renal uptake of these agents and the clearance of simultaneously injected [/sup 99m/Tc]DTPA. The 2-hr organ distribution and urinary excretion of these agents were compared with the corresponding values of DTPA. The differences in clearance between rats with glomerular damage and controls were greater with aminated dextran (mol wt 5000) than with DTPA, confirming previous work with infusions of nonradioactive charged dextrans and neutral inulin. The cationic dextrans appear to reflect the presence or absence of the normal anionic charge of the glomerular membrane as well as changes in filtration rate. Aminated inulin did not differentiate between controls and rats with glomerular disease any better than DTPA, probably because the number of amino groups conjugated was insufficient to produce the charge effect

  19. Uptake and dosimetry of Auger emitting diagnostic radionuclides (in particular indium-111) in human male germ cells

    International Nuclear Information System (INIS)

    Nettleton, J.S.; Lawson, R.S.; Prescott, M.C.; Hoyes, K.P.; Morris, I.D.

    2000-01-01

    This paper concerns the uptake and dosimetry of Auger electron emitting radionuclides which are used during routine diagnostic nuclear medicine procedures, in human testes and spermatozoa (sperm). A computer model was developed to calculate the doses to sperm heads from cellular localisation of the Auger electron emitting radionuclides 99m Tc, 111 In, 123 I and 201 Tl. An assumption of ellipsoidal geometry was made to approximate the sperm head. S Factors were determined for differing sub-cellular localisations of radionuclide. The S-Factors determined were then combined with in-vitro data for quantification of radionuclide uptake for 99m Tc pertechnetate, 111 In chloride and 201 Tl chloride, to estimate in-vivo doses to sperm heads following intravenous administration of radionuclide in typical diagnostic quantities. The uptake and resulting cellular radiation dose of 111 In (from the chloride) was significantly larger than the other radionuclides in the chemical forms investigated. Further investigations were carried out to determine localisation of 111 In on sperm. The results of these experiments indicate that the radiation dose to mature sperm following administration of 111 In pharmaceuticals for diagnostic purposes might be large enough to result in DNA damage which is not expressed until after fertilisation of an oocyte. Consideration should therefore be given to providing some contraceptive advice following diagnostic administrations of this radionuclide. In order to consider the possible effects of these radionuclides on other spermatogenic cells, further studies were undertaken to obtain in-vivo data for quantification of 111 In chloride and 201 Tl chloride uptake into the human testis following intravenous administration. Conventional dosimetry was then used to estimate testicular radiation dose using our values of percentage uptake. The results obtained indicate that the values of testicular radiation doses quoted by ICRP for 111 In might be too low by a factor of 3, whereas those for 201 Tl might be too high by a factor of 4. No data was obtained for uptake by differing germ cell types within the testis and therefore no consideration of dosimetry at the cellular level was possible. It was concluded that uptake of diagnostic Auger emitting radionuclides by male germ cells (and especially sperm) is possible following intravenous administration. In the case of 111 In at least, the resulting cellular radiation dose, calculated to include the contributions of Auger electrons, might be large enough to cause DNA damage with significant biological consequences. (author)

  20. Pre-treatment and follow-up examinations of carcinoid metastases using indium-111-octreotide - rational application of Sandostatin

    International Nuclear Information System (INIS)

    Lipp, R.W.; Hammer, H.F.; Passath, A.; Dobnig, H.; Ramschak-Schwarzer, S.; Stiegler, C.; Leb, G.; Krejs, G.J.

    1993-01-01

    Carcinoids may express somatostatin receptors. Therefore, a somatostatin-analogue, In-111 octreotide (OctreoScan), was used for their demonstration. A total of 6 patients who presented radiologically verified carcinoid-metastases was examined. In order to control tumor progress, 4 of these patients were reexamined within a period of 3 to 11 months. All of the radiological findings were confirmed scintigraphically, except some small retroperitoneally located lymph nodes. The follow-up examinations of 2 patients revealed additional metastases by scintigraphy only. There were no false positive results. These results of OctreoScan-scintigraphy may be used for predicting the success of receptor-specific therapies and therefore, permit the rational and efficient application of Sandostatin. Note: Sandostatin and OctreoScan are registered trademarks. (authors)

  1. Indium-111-labeled white blood cells in the detection of osteomyelitis complicated by a pre-existing condition

    International Nuclear Information System (INIS)

    McCarthy, K.; Velchik, M.G.; Alavi, A.; Mandell, G.A.; Esterhai, J.L.; Goll, S.

    1988-01-01

    Forty-six patients (23M, 23F) ranging in age from 19 to 79 yr with a clinical history of a nonunion fracture, surgery, diabetes or a soft-tissue infection were studied with [ 111 In]oxine WBCs to detect osteomyelitis. There were 27 true-positive, nine true-negative, two false-positive and one false-negative. The false-positives and the false-negative occurred in patients with soft-tissue infections overlying the area of interest. All diagnoses were confirmed by intraoperative bone biopsies and cultures. Bone biopsy and scan were performed within 2 days of each other in 39 patients. The overall sensitivity was 97% (27/28), specificity, 82% (9/11) and the diagnostic accuracy, 92% (36/39). The remaining seven patients had negative [ 111 In]WBC scans several months after positive bone biopsies and definite antibiotic treatment. This suggests that [In]WBC scans become negative after appropriate therapy is undertaken. Interobserver data was obtained from four nuclear physicians of varying experience blinded to clinical information. A high degree of agreement was found in over 90% of the cases. This study demonstrates the utility of [ 111 In]WBC scans in the diagnosis and follow-up of complicated osteomyelitis and a high level of interobserver agreement in scan interpretation

  2. Evaluation of a disturbance of cerebrospinal fluid circulation after pneumococcal meningitis, using a new cysternography method (Indium 111)

    International Nuclear Information System (INIS)

    Sulman, C.; Goudemand, M.; Caron, J.C.

    1974-01-01

    An isotope cisternography using 111 In was performed in a 61 year old woman with pneumococcal meningits. A disturbance of cerebrospinal fluid circulation was exhibited. 111 In was found to be of interest for isotope cisternography. The principal clinical indications of this investigation were summarized [fr

  3. SPECT assay of radiolabeled monoclonal antibodies

    International Nuclear Information System (INIS)

    Jaszczak, R.J.

    1992-02-01

    The long-term goal of this research project is to develop methods to improve the utility of single photon emission computed tomography (SPECI) to quantify the biodistribution of monoclonal antibodies (MoAbs) labeled with clinically relevant radionuclides ( 123 I, 131 I, and 111 In) and with another radionuclide, 211 At, recently used in therapy. We describe here our progress in developing quantitative SPECT methodology for 111 In and 123 I. We have focused our recent research thrusts on the following aspects of SPECT: (1) The development of improved SPECT hardware, such as improved acquisition geometries. (2) The development of better reconstruction methods that provide accurate compensation for the physical factors that affect SPECT quantification. (3) The application of carefully designed simulations and experiments to validate our hardware and software approaches

  4. Monoclonal antibodies and Fc fragments for treating solid tumors

    Directory of Open Access Journals (Sweden)

    Eisenbeis AM

    2012-01-01

    Full Text Available Andrea M Eisenbeis, Stefan J GrauDepartment of Neurosurgery, University Hospital of Cologne, Cologne, GermanyAbstract: Advances in biotechnology, better understanding of pathophysiological processes, as well as the identification of an increasing number of molecular markers have facilitated the use of monoclonal antibodies and Fc fragments in various fields in medicine. In this context, a rapidly growing number of these substances have also emerged in the field of oncology. This review will summarize the currently approved monoclonal antibodies used for the treatment of solid tumors with a focus on their clinical application, biological background, and currently ongoing trials.Keywords: targeted therapy, monoclonal antibodies, cancer, biological therapy

  5. The detection of ovarian cancer using 123I monoclonal antibody

    International Nuclear Information System (INIS)

    Granowska, M.; Britton, K.E.; Shepherd, J.

    1984-01-01

    The technique of the production of monoclonal antibodies is described. Antibodies show reactivity with epithelial surfaces of cancer of breast, colon and ovary. The iodogen reaction is used for labelling monoclonal antibodies with 123 I. Description of labelling technique and quality control. After intravenous injection of 74 MBq 123 I-labelled monoclonal antibody (0.5 mg) static camera images of the abdomen were recorded at 10 min, 4 and 22 hours in anterior and posterior position. 20 out of 22 patients with ovarian cancer with and without metastases were correctly diagnosed and confirmed at surgery. (author)

  6. Monoclonal gammopathy: a diagnosis for to keep in mind

    International Nuclear Information System (INIS)

    Howland Alvarez, Ivon; Figueredo Peguero, Yrving; Luna Conde, Clara

    2011-01-01

    How to identify monoclonal gammopathies at risk for progression has been studied for the last year. 40 patients were studied in which a monoclonal band had been detected, in some of the cases de novo. The electrophoresis was performed in the Hydrasys system. Of the total of electrophoresis carried out, the 14% was monoclonal gammopathy. In 36% a diagnostic assumption was not stated. Most frequent diagnosis in the group of patients with a diagnosis was multiple myeloma. Average age of patients was 61.5 years and there were differences among percentages for sex

  7. Monoclonal gammopathy: a diagnosis for to keep in mind; Gammapatia monoclonal: un diagnostico a tener en cuenta

    Energy Technology Data Exchange (ETDEWEB)

    Howland Alvarez, Ivon; Figueredo Peguero, Yrving; Luna Conde, Clara, E-mail: ihowlanda@infomed.sld.cu [Centro de Investigaciones Medico Quirurgicas, La Habana (Cuba); others, and

    2011-07-01

    How to identify monoclonal gammopathies at risk for progression has been studied for the last year. 40 patients were studied in which a monoclonal band had been detected, in some of the cases de novo. The electrophoresis was performed in the Hydrasys system. Of the total of electrophoresis carried out, the 14% was monoclonal gammopathy. In 36% a diagnostic assumption was not stated. Most frequent diagnosis in the group of patients with a diagnosis was multiple myeloma. Average age of patients was 61.5 years and there were differences among percentages for sex.

  8. [International classification of various types of monoclonal antibodies].

    Science.gov (United States)

    Scheen, A J

    2009-01-01

    Significant advances in the development of monoclonal antibodies ("mabs") have been acknowledged during the last two decades. Successive developments led to the marketing of murine antibodies ("o-mab" first, followed by chimeric antibodies ("xi-mab"), humanised antibodies ("zu-mab") and, finally, human monoclonal antibodies ("u-mab"). In order to facilitate the distinction between the various monoclonal antibodies used in clinical practice, an international nomenclature has been proposed with the use of a specific suffix corresponding to the origine/source of "mabs" preceded by an infix referring to the medicine's target. The efforts in developing new types of monoclonal antibodies aimed at improving their pharmacokinetics (longer half-life), pharmacodynamics (better efficacy because of stronger affinity to human receptor), and safety profile (less antigenic and immunogenic reactions). These progresses could be obtained thanks to the remarkable development of molecular biotechnology.

  9. Monoclonal antibody 6E4 against human GAPDHS protein

    Czech Academy of Sciences Publication Activity Database

    Dorosh, Andriy

    2011-01-01

    Roč. 30, č. 3 (2011), s. 321-321 ISSN 1554-0014 Institutional research plan: CEZ:AV0Z50520701 Keywords : Monoclonal antibody * GAPDHS Subject RIV: EI - Biotechnology ; Bionics Impact factor: 0.417, year: 2011

  10. DEVELOPMENT OF MONOCLONAL ANTIBODIES AGAINST FATHEAD MINNOW (PIMEPHALES PROMELAS) VITELLOGENIN

    Science.gov (United States)

    We have obtained a panel of monoclonal antibodies directed against fathead minnow vitellogenin (Vtg) for use in sensitive ELISAs to quantify the response of exposure in vivo to estrogen or estrogen mimics.

  11. Monoclonal antibodies in clinical diagnosis: A brief review application

    African Journals Online (AJOL)

    SERVER

    2008-04-17

    Apr 17, 2008 ... More than 100 different monoclonal antibody diagnostic products are ... are produced by in vitro and in vivo method but have advantages and some disadvantages. .... replication and differentiation, advancing our knowledge.

  12. Biodistribution mechanisms of therapeutic monoclonal antibodies in health and disease.

    Science.gov (United States)

    Tabrizi, Mohammad; Bornstein, Gadi Gazit; Suria, Hamza

    2010-03-01

    The monoclonal antibody market continues to witness an impressive rate of growth and has become the leading source of expansion in the biologic segment within the pharmaceutical industry. Currently marketed monoclonal antibodies target a diverse array of antigens. These antigens are distributed in a variety of tissues such as tumors, lungs, synovial fluid, psoriatic plaques, and lymph nodes. As the concentration of drug at the proximity of the biological receptor determines the magnitude of the observed pharmacological responses, a significant consideration in effective therapeutic application of monoclonal antibodies is a thorough understanding of the processes that regulate antibody biodistribution. Monoclonal antibody distribution is affected by factors such as molecular weight, blood flow, tissue and tumor heterogeneity, structure and porosity, target antigen density, turnover rate, and the target antigen expression profile.

  13. Identification and typing of herpes simplex viruses with monoclonal antibodies.

    OpenAIRE

    Balachandran, N; Frame, B; Chernesky, M; Kraiselburd, E; Kouri, Y; Garcia, D; Lavery, C; Rawls, W E

    1982-01-01

    Monoclonal antibodies which reacted with type-specific antigens of herpes simplex virus type 2 or with antigens shared by herpes simplex virus types 1 and 2 were used in an indirect immunofluorescence assay to type virus isolates and to detect viral antigens in cells obtained from herpetic lesions. Complete concordance was obtained for 42 isolates typed by endonuclease restriction analysis of viral DNA and by indirect immunofluorescence with monoclonal antibodies. Examination of a limited num...

  14. Rapid screening of monoclonal antibodies: new 'microstick' radioimmunoassay

    International Nuclear Information System (INIS)

    Scheinberg, D.A.; Strand, M.; Wilsnack, R.

    1983-01-01

    A new system for assaying monoclonal antibodies consisting of an 8 x 12 array of sticks which fits into a 96-well microtiter plate is described. Tests using virus specific monoclonal antibodies and virus proteins demonstrated sensitivity equivalent to the conventional microtiter plate assay. Antibody production, antigen specific antibody, and immunoglobulin isotypes could be measured under sterile conditions directly in the original fusion mixture wells and much greater rapidity than with the microtiter plate assay. (Auth.)

  15. Rat Monoclonal Antibodies Specific for LST1 Proteins

    OpenAIRE

    Schiller, Christian; Nitschké, Maximilian J. E.; Seidl, Alexander; Kremmer, Elisabeth; Weiss, Elisabeth H.

    2009-01-01

    The LST1 gene is located in the human MHC class III region and encodes transmembrane and soluble isoforms that have been suggested to play a role in the regulation of the immune response and are associated with inflammatory diseases such as rheumatoid arthritis. Here we describe the generation and characterization of the first monoclonal antibodies against LST1. Two hybridoma lines secreting monoclonal antibodies designated 7E2 and 8D12 were established. The 7E2 antibody detects recombinant a...

  16. Breast cancer imaging with mouse monoclonal antibodies

    Energy Technology Data Exchange (ETDEWEB)

    Major, P.; Wang Taqui; Unger, M.; Rosenthall, L.

    1989-10-01

    The localization of /sup 111/In-labelled MA5 monoclonal antibody, reactive with a breast tumor associated antigen, was studied in 17 patients. MA5 was selected because (1) it reacts with >95% of primary and metastatic lesions, (2) the recognized antigen is present on the cell surface in vivo and (3) MA5 gives excellent localization in human breast tumor xenografts. Each patient received 2 mg antibody labeled with 5 mCi /sup 111/In and in some cases, 3 mg or 18 mg unlabeled carrier antibody. No serious allergic reactions were noted. There was a large uptake in the liver, less significant uptake in the spleen and bone and minimal accumulation in the bowel. Bone lesions, primary tumors, soft tissue recurrences and lung metastases larger than 3 cm diameter were imaged, while only 1 lesion smaller than 3 cm was detected. Non specific accumulation of tracer was noted at the site of a port-a-cath, in a hematoma, in fibrocystic lesions, and at sites of previous radiation treatment. Extensive fibrosis and poor vascularization characteristic of breast tumors may explain in part the limited sensitivity of the imaging. (orig.).

  17. Monoclonal antibodies based on hybridoma technology.

    Science.gov (United States)

    Yagami, Hisanori; Kato, Hiroshi; Tsumoto, Kanta; Tomita, Masahiro

    2013-03-01

    Based on the size and scope of the present global market for medicine, monoclonal antibodies (mAbs) have a very promising future, with applications for cancers through autoimmune ailments to infectious disease. Since mAbs recognize only their target antigens and not other unrelated proteins, pinpoint medical treatment is possible. Global demand is dramatically expanding. Hybridoma technology, which allows production of mAbs directed against antigens of interest is therefore privileged. However, there are some pivotal points for further development to generate therapeutic antibodies. One is selective generation of human mAbs. Employment of transgenic mice producing human antibodies would overcome this problem. Another focus is recognition sites and conformational epitopes in antigens may be just as important as linear epitopes, especially when membrane proteins such as receptors are targeted. Recognition of intact structures is of critical importance for medical purposes. In this review, we describe patent related information for therapeutic mAbs based on hybridoma technology and also discuss new advances in hybridoma technology that facilitate selective production of stereospecific mAbs.

  18. Monoclonal antibody to DNA containing thymine glycol

    Energy Technology Data Exchange (ETDEWEB)

    Leadon, S A; Hanawalt, P C [Stanford Univ., CA (USA). Dept. of Biological Sciences

    1983-08-01

    Exposure of DNA to ionizing or near ultraviolet radiation modifies thymine to form ring-saturated products. One of the major products formed is 5,6-dihydroxy-5.6-dihydrothymine (thymine glycol). Thymine glycol can also be selectively formed by oxidizing DNA with OsO/sub 4/. We have isolated hybrids that produce monoclonal antibodies against thymine glycol by fusing mouse myeloma cells (P3X63-Ag8-6.5.3) with spleen cells from BALB/c mice immunized with OsO/sub 4/-oxidized poly(dT) complexed with methylated bovine serum albumin. This report describes the characterization of the antibody from one hybridoma using a competitive enzyme-linked immunosorbent assay (ELISA). The antibody reacted with both single- and double-stranded DNA treated with OsO/sub 4/, and with OsO/sub 4/-treated poly(dA-dT) and poly(dT); it did not crossreact with unmodified or apurinic DNA. It also reacted with DNA treated with H/sub 2/O/sub 2/ or with ..gamma..-rays at doses as low as 250 rad. We were able to detect 2 fmoles of thymine glycol in OsO/sub 4/-treated DNA and could quantitate 1 thymine glycol per 220000 thymines. Using the antibody and the ELISA, the formation and removal of thymine glycol was examined in cultures of African green monkey cells irradiated with 25 krad of ..gamma..-rays. The antibody reactive sites produced by irradiation (8.5 per 10/sup 6/ thymines) were efficiently removed from the cellular DNA.

  19. Novel monoclonal treatments in severe asthma.

    Science.gov (United States)

    Meteran, Howraman; Meteran, Hanieh; Porsbjerg, Celeste; Backer, Vibeke

    2017-12-01

    To provide a general overview of the current biological treatments and discuss their potential anti-asthmatic effects. We reviewed articles in PubMed found using the search words "Asthma/therapy AND antibodies, monoclonal/therapeutic use AND cytokines." Only articles published in English since 2000 were considered. The search identified 29 studies; 8 additional studies were found by hand search, generating 37 studies. Of the 37 studies investigating biological treatments of asthma, 5 were on the effects of anti-IgE (omalizumab); 12 on anti-IL-5; 8 on anti-IL-13; 5 on anti-IL-4R-α; 3 on anti-IL-9; one on TNF-α; one on anti-IL-2R-α; one on TSLP (Thymic Stromal Lymphopoietin); and one on OX40L. Sample sizes ranged from 3 to 943 participants. Studies of therapies targeting IgE, IL-2, IL4R-α, IL-5, and IL-13 showed some efficacy, whereas those targeting TSLP, IL-9, and TNF-α lacked convincing effectiveness. Research on the biological treatment of asthma shows promising results. While anti-IgE (omalizumab) has been used in the treatment of asthma for some years, anti-IL-5 has recently been approved for use. The efficacy of results of other large studies with a longer duration is needed to draw a firm conclusion. Such studies should not only focus on clinical outcomes, but also consider asthma-related quality of life. Knowledge on the asthma phenotypes and identification of biomarkers associated with these will be useful for physicians considering the right treatment for the asthma patient.

  20. Monoclonal antibodies to drosophila cytochrome P-450's

    International Nuclear Information System (INIS)

    Sundseth, S.S.; Kennel, S.J.; Waters, L.C.

    1987-01-01

    Hybridomas producing monoclonal antibodies were prepared by the fusion of SP2/0 myeloma cells and spleen cells from a female BALB/c mouse immunized by cytochrome P-450-A and P-450-B purified from Drosophila Hikone-R (BG) microsomes. P-450-A and P-450-B are electrophoretically distinct subsets of Drosophila P-450. P-450-A is ubiquitous among strains tested, while P-450-B is present in only a few strains displaying unique enzyme activities and increased insecticide resistance. The Oregon-R strain contains only cytochromes P-450-A and is susceptible to insecticides. The authors Hikone-R (BG) strain expresses both cytochromes P-450-A and P-450-B and is insecticide resistant. Antibody producing hybridomas were detected in a solid-phase radioimmunoassay (RIA) by binding to Hikone-R (BG) or Oregon-R microsomes. Four independent hybridomas were identified as producing monoclonal antibodies that recognized proteins in the P-450 complex by immunoblot experiments. Three monoclonal antibodies recognized P-450-A proteins, while one monoclonal antibody bound predominantly P-450-B. This monoclonal antibody also recognized southern armyworm (Spodoptera eridania, Cramer) microsomal proteins

  1. An intelligent identification algorithm for the monoclonal picking instrument

    Science.gov (United States)

    Yan, Hua; Zhang, Rongfu; Yuan, Xujun; Wang, Qun

    2017-11-01

    The traditional colony selection is mainly operated by manual mode, which takes on low efficiency and strong subjectivity. Therefore, it is important to develop an automatic monoclonal-picking instrument. The critical stage of the automatic monoclonal-picking and intelligent optimal selection is intelligent identification algorithm. An auto-screening algorithm based on Support Vector Machine (SVM) is proposed in this paper, which uses the supervised learning method, which combined with the colony morphological characteristics to classify the colony accurately. Furthermore, through the basic morphological features of the colony, system can figure out a series of morphological parameters step by step. Through the establishment of maximal margin classifier, and based on the analysis of the growth trend of the colony, the selection of the monoclonal colony was carried out. The experimental results showed that the auto-screening algorithm could screen out the regular colony from the other, which meets the requirement of various parameters.

  2. Exploration of novel strategies to enhance monoclonal antibodies targeting

    International Nuclear Information System (INIS)

    Khawli, L.A.; Epstein, A.L.

    1997-01-01

    This paper highlights the major obstacles and prospects of antibody targeting for the radio imaging and therapy of human malignant lymphomas and more challenging solid tumors. To improve the therapeutic potential of monoclonal antibodies, the authors have focused their attention on the development of new and successful methods to augment antibody uptake in the tumor. These approaches include the use of radiolabeled streptavidin to target biotinylated monoclonal antibodies already bound to tumor, pretreatment with vasoactive immunoconjugates, and the use of chemically modified antibodies. Because of the promising preclinical data obtained with these three newer approaches, plans are underway to test them in the clinic. More generally, these approaches are applicable to the use of other monoclonal antibody/tumor systems for the diagnosis and therapy of human cancers and related diseases

  3. Radioimmunoimaging of experimental gliomas using radiolabelled monoclonal antibodies

    International Nuclear Information System (INIS)

    Glaessner, H.

    1986-01-01

    The biodistribution and tumour uptake of radiolabelled (131 I) glioma-seeking monoclonal antibodies (14 AC1) and their F(ab') 2 fragments were investigated in nude mice having received glioma transplants. Radioimmunoimaging by external scintigraphy at 48 and 96 hours pointed to a superior tumour localisation by the fragments that was clearly related to the dose. Wholebody determinations of the biokinetic behaviour led to the following results: Faster clearance anc more ready elimination from the blood pool for the fragments, preferential uptake in the tumour; intact antibodies; binding in the liver, spleen and lungs. The study confirmed the value of fragments of monoclonal antibodies in the diagnosis of tumours and pointed to the possibility of using intact monoclonal antibodies as carriers of radioisotopes and cytotoxic drugs within the scope of therapeutic programmes. (TRV) [de

  4. Efficacy of Wnt-1 monoclonal antibody in sarcoma cells

    International Nuclear Information System (INIS)

    Mikami, Iwao; Koizumi, Kiyoshi; Jablons, David M; You, Liang; He, Biao; Xu, Zhidong; Batra, Sonny; Lee, Amie Y; Mazieres, Julien; Reguart, Noemi; Uematsu, Kazutsugu

    2005-01-01

    Sarcomas are one of the most refractory diseases among malignant tumors. More effective therapies based on an increased understanding of the molecular biology of sarcomas are needed as current forms of therapy remain inadequate. Recently, it has been reported that Wnt-1/β-catenin signaling inhibits apoptosis in several cancers. In this study, we investigated the efficacy of a monoclonal anti-Wnt-1 antibody in sarcoma cells. We treated cell lines A-204, SJSA-1, and fresh primary cultures of lung metastasis of sarcoma with a monoclonal anti-Wnt-1 antibody. Wnt-1 siRNA treatment was carried out in A-204. We assessed cell death using Crystal Violet staining. Apoptosis induction was estimated by flow cytometry analysis (Annexin V and PI staining). Cell signaling changes were determined by western blotting analysis. We detected Wnt-1 expression in all tissue samples and cell lines. Significant apoptosis induction was found in monoclonal anti-Wnt-1 antibody treated cells compared to control monoclonal antibody treated cells (p < 0.02). Similarly, we observed increased apoptosis in Wnt-1 siRNA treated cells. Blockade of Wnt-1 signaling in both experiments was confirmed by analyzing intracellular levels of Dishevelled-3 and of cytosolic β-catenin. Furthermore, the monoclonal anti-Wnt-1 antibody also induced cell death in fresh primary cultures of metastatic sarcoma in which Wnt-1 signaling was active. Our results indicate that Wnt-1 blockade by either monoclonal antibody or siRNA induces cell death in sarcoma cells. These data suggest that Wnt-1 may be a novel therapeutic target for the treatment of a subset of sarcoma cells in which Wnt-1/β-catenin signaling is active

  5. Making Recombinant Monoclonal Antibody And Radiolabelling For Medical Purpose

    International Nuclear Information System (INIS)

    Nguyen Thi Thu; Duong Van Dong; Vo Thi Cam Hoa; Bui Van Cuong; Chu Van Khoa; Vu Bich Huong; Le Quang Huan

    2008-01-01

    Recombinant monoclonal antibody labeling with 131 I specific to tumor cell has been studied and prepared for treatment of Hodgkin lymphoma. In this study, a recombinant monoclonal antibody with two specific properties is a hybrid molecule created by coupling an antibody variable fragments with peptide melittin. The gene coding the antibody fragment has been obtained from human synthetic Fv libraries using for panning and screening on populations of lymphocytes fragmented from human blood cells with Hodgkin diseases. The gene encoding peptit melittin has been cloned from honeybee Apis cerana DNA. The gene coding recombinant monoclonal antibody has been expressed in E.coli BL21 (DE3) at 37 o C and was induced with 0.6 mM IPTG. The recombinant compound has been purified by affinity chromatography with HiTrap affinity column. The obtained recombinant monoclonal antibody has showed cytolytic activities when added to cell culture medium for LU cancer cell line with the amount of 100 - 200 mg/ml. This monoclonal antibody is labeled with 131 I using chloramine T procedure. ChT mass for the oxidation of 50 μg monoclonal antibody in 76 MBq was 10 μg. Sodium metabisulfite was used as a reducing agent. Reaction time was above 3 mins. The radiochemical purity was determined using electrophoresis and TLC methods. Radiochemical yield was > 97%. Radiochemical purity after purification was > 99%. Nuclear purity was > 99%. Stability of the label antibody was 12 days. This is the product promise potential used in the diagnostic and therapeutic of Hodgkin lymphoma. (author)

  6. High throughput production of mouse monoclonal antibodies using antigen microarrays

    DEFF Research Database (Denmark)

    De Masi, Federico; Chiarella, P.; Wilhelm, H.

    2005-01-01

    Recent advances in proteomics research underscore the increasing need for high-affinity monoclonal antibodies, which are still generated with lengthy, low-throughput antibody production techniques. Here we present a semi-automated, high-throughput method of hybridoma generation and identification....... Monoclonal antibodies were raised to different targets in single batch runs of 6-10 wk using multiplexed immunisations, automated fusion and cell-culture, and a novel antigen-coated microarray-screening assay. In a large-scale experiment, where eight mice were immunized with ten antigens each, we generated...

  7. Monoclonal anti-melanoma antibodies and their possible clinical use

    International Nuclear Information System (INIS)

    Hellstroem, K.E.; Hellstroem, Ingegerd; Washington Univ., Seattle; Washington Univ., Seattle

    1985-01-01

    Cell surface antigens of human melanoma, as defined by monoclonal antibodies, are discussed and in particular the three antigens p97, a GD3 ganglioside and a proteoglycan. The potential diagnostic uses of antibodies to melanoma antigens are reviewed including in vitro diagnosis by immuno-histology, in vitro diagnosis by serum assays and in vivo diagnosis by tumour imaging using radioactively labelled antibodies. The potential therapeutic uses of monoclonal antibodies to melanoma antigens are also reviewed including targets for antibody therapy, the use of antibodies alone, radiolabelled antibodies, antibody-toxin conjugates, antibody-drug conjugates, anti-idiotypic antibodies and vaccines. (UK)

  8. ERBB oncogene proteins as targets for monoclonal antibodies.

    Science.gov (United States)

    Polanovski, O L; Lebedenko, E N; Deyev, S M

    2012-03-01

    General properties of the family of tyrosine kinase ERBB receptors are considered in connection with their role in the generation of cascades of signal transduction in normal and tumor cells. Causes of acquisition of oncogene features by genes encoding these receptors and their role in tumorigenesis are analyzed. Anti-ERBB monoclonal antibodies approved for therapy are described in detail, and mechanisms of their antitumor activity and development of resistance to them are reviewed. The existing and the most promising strategies for creating and using monoclonal antibodies and their derivatives for therapy of cancer are discussed.

  9. Production and radioiodination of monoclonal antibodies and its applications in nuclear medicine

    International Nuclear Information System (INIS)

    Toledo e Souza, I.T. de; Okada, H.

    1988-12-01

    The basis of the monoclonal antibody production methodology, some immunological concepts which are important for the understanding of what is a Monoclonal Antibody, its radioiodination and acceptance as receptor-specific radiopharmaceuticals in nuclear medicine are reviewed. (author) [pt

  10. Monoclonal antibodies: an overview of their advantages and limitations in nuclear medicine

    International Nuclear Information System (INIS)

    Revillard, J.P.; Cohen, J.

    1982-01-01

    The following topics were reviewed: antigen recognition by the immune system; development of immunoassays for antigenic components of biological fluids; monoclonal antibodies against infectious agents; monochonal antibodies against tumor and differentiation antigens; human monoclonal antibodies

  11. Monoclonal antibodies in animal production : their use in diagnostics and passive immunization

    NARCIS (Netherlands)

    Booman, P.

    1989-01-01

    One of the landmarks in immunology was the invention and development of monoclonal antibody-secreting hybridomas by Milstein and his coworkers. The enormous promise of monoclonal antibody technology, which became apparent soon after its discovery, may explain the unusual speed with which monoclonal

  12. Production of monoclonal antibodies against Mycobacterium leprae and armadillo-derived mycobacteria

    NARCIS (Netherlands)

    Kolk, A. H.; Ho, M. L.; Klatser, P. R.; Eggelte, T. A.; Portaels, F.

    1985-01-01

    Six monoclonal antibodies to Mycobacterium leprae and armadillo-derived mycobacteria were produced. The monoclonal antibodies were characterized by an immunofluorescence assay using 22 mycobacterial strains. One monoclonal antibody, F47-21-3, reacted only with M. leprae; two, F45-9 and F45-15,

  13. Production of yam mosaic virus monoclonal antibodies in mice ...

    African Journals Online (AJOL)

    Administrator

    2011-09-19

    Sep 19, 2011 ... 4AVRDC-The World Vegetable Center, Shanhua, Taiwan. Accepted 11 August, 2011. Yam mosaic virus (YMV) ... leaves and non-infected tissue culture yam leaves. The antibody produced had a titre of ... systems for in-vitro production of monoclonal antibodies, such as standard tissue culture techniques,.

  14. Monoclonal antibodies specific for the organophosphate pesticide azinphos-methyl

    NARCIS (Netherlands)

    Jones, WT; Harvey, D; Jones, SD; Ryan, GB; Wynberg, H; TenHoeve, W; Reynolds, PHS

    1995-01-01

    2-(2-Mercapto-5-methyl-1,3,2-dioxaphosphorinan-5-yl,2-sulphide) methoxyacetic acid has been synthesized and used to prepare an azinphos hapten and protein conjugates. Monoclonal antibodies of high affinity against the pesticide azinphos-methyl were prepared from mice immunized with the

  15. Application of murine monoclonal antibodies to the serodiagnosis of tuberculosis

    International Nuclear Information System (INIS)

    Ivanyl, J.; Coates, A.R.M.; Krambovitis, E.

    1982-01-01

    The immune response during infectious diseases leads to a rise in antibody titre to the various different antigenic determinants of the causative organism. The response is further complicated by the fact that it is relatively unusual for one individual to respond to all antigenic components of an organism. Demonstration of the specific immune response of an infected host by serological tests is often hampered by the broad cross-reactivity between several bacterial antigens. The authors report on a serodiagnostic application of murine monoclonal antibodies (MAB), specific for a human pathogen, M. tuberculosis by a technique which is applicable in principle to the serodiagnosis of many other infectious diseases. The serum diagnostic test is based on the competitive inhibition by human sera of the binding of 125 I-labelled murine monoclonal antibodies to M. tuberculosis-coated polyvinyl plates. Five monoclonal antibodies binding to distinct antigenic determinants of the organism were used as structural probes which conferred their stringent combining site specificities to the polyclonal mixture of antibodies from patients' sera. When compared with healthy controls, increased titres of inhibitory antibodies were found in about 70% of patients with active tuberculosis. The diagnostic value of the individual monoclonal antibodies as well as the benefit from the use of multiple specificity probes has been qualified

  16. Radioimmunodetection of human melanoma tumor xenografts with human monoclonal antibodies

    International Nuclear Information System (INIS)

    Gomibuchi, Makoto; Saxton, R.E.; Lake, R.R.; Katano, Mitsuo; Irie, R.F.

    1986-01-01

    A human IgM monoclonal antibody has been established that defines a tumor-associated membrane antigen expressed on human melanoma cells. The antigen has been identified as the ganglioside GD2. In this paper, the authors describe the potential usefulness of the human monoclonal antibody for radioimaging. Nude mice bearing tumors derived from a human melanoma cell line were used as a model. Antibody activity was degradated significantly after labeling with 131 I by the use of a modified chloramine-T method. After testing various concentrations, labeled antibody of a specific activity of 2.8μCi/μg produced the best results. Balb/c nude mice bearing a GD2-positive M14 melanoma cell line were injected with 10-30μg of labeled antibody, and its radiolocalization in different organs and in the whole body were evaluated. The best tumor image was obtained on Day 6. The labeled antibody uptake ratio between tumor and muscle was 9.2:1; the ratio between tumor and liver was 1.4:1. These studies represent the first report of experimental tumor imaging with human monoclonal antibody. Human monoclonals will probably prove to be superior reagents for tumor imaging in melanoma patients if the problem of anti-body radiolysis is resolved. (author)

  17. Production and characterization of monoclonal antibodies against mink leukocytes

    DEFF Research Database (Denmark)

    Chen, W.S.; Pedersen, Mikael; Gram-Nielsen, S.

    1997-01-01

    Three monoclonal antibodies (mAbs) were generated against mink leukocytes. One antibody reacted with all T lymphocytes, one with all monocytes and one had platelet reactivity. Under reducing conditions, the T lymphocyte reactive antibody immunoprecipitated 18 kDa, 23 kDa, 25 kDa and 32-40 kDa pol...

  18. Monoclonal antibodies for the detection of Puccinia striiformis urediniospores

    DEFF Research Database (Denmark)

    Skottrup, Peter; Frøkiær, Hanne; Hearty, Stephen

    2007-01-01

    The fungal pathogen Pst causes yellow rust disease in wheat plants leading to crop losses. The organism spreads by releasing wind-dispersed urediniospores from infected plants. In this study a library of novel monoclonal antibodies (mAbs) was developed against Pst urediniospores. Nine mAb-produci...

  19. Characterization of Binding Epitopes of CA125 Monoclonal Antibodies

    DEFF Research Database (Denmark)

    Marcos-Silva, Lara; Narimatsu, Yoshiki; Halim, Adnan

    2014-01-01

    The most used cancer serum biomarker is the CA125 immunoassay for ovarian cancer that detects the mucin glycoprotein MUC16. Several monoclonal antibodies (mAbs) including OC125 and M11 are used in CA125 assays. However, despite considerable efforts, our knowledge of the molecular characteristics...

  20. Iodine-based contrast media, multiple myeloma and monoclonal gammopathies

    DEFF Research Database (Denmark)

    Stacul, Fulvio; Bertolotto, Michele; Thomsen, Henrik S

    2018-01-01

    OBJECTIVES: Many radiologists and clinicians still consider multiple myeloma (MM) and monoclonal gammopathies (MG) a contraindication for using iodine-based contrast media. The ESUR Contrast Media Safety Committee performed a systematic review of the incidence of post-contrast acute kidney injury...

  1. Sensitive chain specific radioimmunoassay for human immunoglobulins using monoclonal antibodies

    Energy Technology Data Exchange (ETDEWEB)

    Sikora, K; Alderson, T St.J.; Ellis, J [Ludwig Institute for Cancer Research, Cambridge (UK)

    1983-02-25

    A sensitive radioimmunoassay is described for human immunoglobulins. This solid-phase assay uses commercially available monoclonal antibodies and is specific for different Ig chain types. Levels of less than 20 ng/ml Ig are detectable. The assay is suitable for the analysis of human hybridoma supernatants.

  2. Generation and Characterization of Novel Human IRAS Monoclonal Antibodies

    Directory of Open Access Journals (Sweden)

    Bo Wang

    2009-01-01

    Full Text Available Imidazoline receptors were first proposed by Bousquet et al., when they studied antihypertensive effect of clonidine. A strong candidate for I1R, known as imidazoline receptor antisera-selected protein (IRAS, has been cloned from human hippocampus. We reported that IRAS mediated agmatine-induced inhibition of opioid dependence in morphine-dependent cells. To elucidate the functional and structure properties of I1R, we developed the newly monoclonal antibody against the N-terminal hIRAS region including the PX domain (10–120aa through immunization of BALB/c mice with the NusA-IRAS fusion protein containing an IRAS N-terminal (10–120aa. Stable hybridoma cell lines were established and monoclonal antibodies specifically recognized full-length IRAS proteins in their native state by immunoblotting and immunoprecipitation. Monoclonal antibodies stained in a predominantly punctate cytoplasmic pattern when applied to IRAS-transfected HEK293 cells by indirect immunofluorescence assays and demonstrated excellent reactivity in flow immunocytometry. These monoclonal antibodies will provide powerful reagents for the further investigation of hIRAS protein functions.

  3. Generation and characterization of a monoclonal antibody to ...

    African Journals Online (AJOL)

    Penicillic acid is one of the main mycotoxins in moldy feedstuff and has toxic effect on livestock and poultry and probably humans due to food chain transmission. The objective of this study was to generate and characterize a monoclonal antibody to penicillic acid for the efficient detection of penicillic acid from Penicillium ...

  4. Monoclonal antibodies AC-43 and AC-29 disrupt Plasmodium vivax ...

    Indian Academy of Sciences (India)

    Prakash

    malaria vaccines that block the transmission of parasites by mosquito vectors ... A repertoire of monoclonal antibodies (mAbs) was generated against the midgut proteins of Anopheles culicifacies ... from the midgut protein extract, as indicated by western blot analysis. Similarly .... 2.2 Antigen preparation and immunization.

  5. Monoclonal antibodies to Herpes Simplex Virus Type 2

    International Nuclear Information System (INIS)

    McLean-Pieper, C.S.

    1982-01-01

    In this thesis the production and characterisation of monoclonal antibodies to Herpes Simplex Virus Type 2 is described. The development of a suitable radioimmunoassay for the detection of anti-HSV-2 antibodies, and the selection of an optimal immunisation schedule, is given. Three assay systems are described and their reliability and sensitivity compared. (Auth.)

  6. MONOCLONAL ANTIBODIES TO IDENTIFY TOMATO MOSAIC TOBAMOVIRUS (TOMV

    Directory of Open Access Journals (Sweden)

    Duarte Keila M.R.

    2001-01-01

    Full Text Available Monoclonal antibodies were obtained against Tomato mosaic tobamovirus (ToMV isolated in Brazil. One antibody (8G7G2 isotyped as IgG2b (kappa light chain showed strong specificity and very low cross reaction with the Tobacco mosaic virus (TMV. It can be used in identification of tomato mosaic virus (ToMV.

  7. Monoclonal antibodies against human trophoblast in female infertility

    Czech Academy of Sciences Publication Activity Database

    Sedláková, Alena; Elzeinová, Fatima; Bukovský, A.; Madar, J.; Ulčová-Gallová, Z.; Pěknicová, Jana

    2005-01-01

    Roč. 54, č. 3 (2005), s. 159 ISSN 0271-7352. [European Congress of Reproductive Immunology /3./. 05.09.11-05.09.15, Essex] R&D Projects: GA MZd(CZ) NR7838 Institutional research plan: CEZ:AV0Z50520514 Keywords : monoclonal antibodies * female infertility * trophoblast Subject RIV: EB - Genetics ; Molecular Biology

  8. Monoclonal antibodies to human chorionic gonadotropin and their application to two-site sandwich radioimmunoassay

    International Nuclear Information System (INIS)

    Mizuchi, A.; Iio, M.; Miyachi, Y.

    1984-01-01

    Monoclonal antibodies were prepared against human chorionic gonadotropin (HCG). One monoclonal antibody recognized a conformational determinant expressed only on native HCG molecule and another monoclonal antibody had the specificity for the epitopes located on the β-subunit of HCG. Monoclonal antibodies reacting with different antigenic determinants on the HCG molecule were used to develop a simplified 2-site sandwich radioimmunoassay in which one monoclonal antibody was immobilized and another labeled with 125 iodine. This assay was highly specific for HCG and there was no cross-reactivity with α,β-subunit of HCG, luteinizing hormone and follicle stimulating hormone. (Auth.)

  9. Monoclonal antibodies for radioimmunodetection of tumours and for targeting

    International Nuclear Information System (INIS)

    Baldwin, R.W.; Embleton, M.J.; Pimm, M.V.

    1983-01-01

    A monoclonal antibody 791T/36 prepared against human osteogenic sarcoma has been used to detect primary and metastatic colorectal carcinomas by external imaging of patients following injection of 131 I-labelled antibody. In 10 of 11 patients radiolabelled 791T/36 antibody localized in tumours, the tumour/non tumour ratio of radioactivity ranging from 1.5:1 to 8.1. 791T/36 antibody was also evaluated for its potential for targeting anti-tumour agents including cytotoxic drugs (Vindesine) and immunomodulating agents (interferon). Vindesine-791T/36 conjugates were preferentially cytotoxic in vitro for target cells expressing the 791T/36 anti-body defined antigen. Also interferon conjugated to 791T/36 antibody, like free interferon activated peripheral blood natural killer cell activity. These in vitro tests together with related studies on antibody localization in vivo indicate the potential of monoclonal antibody targeting of anti-tumour agents

  10. Enzymatic Production of Monoclonal Stoichiometric Single-Stranded DNA Oligonucleotides

    Science.gov (United States)

    Ducani, Cosimo; Kaul, Corinna; Moche, Martin; Shih, William M.; Högberg, Björn

    2013-01-01

    Single-stranded oligonucleotides are important as research tools as probes for diagnostics and gene therapy. Today, production of oligonucleotides is done via solid-phase synthesis. However, the capabilities of current polymer chemistry are limited in comparison to what can be produced in biological systems. The errors in synthetic DNA increases with oligonucleotide length, and sequence diversity can often be a problem. Here, we present the Monoclonal Stoichiometric (MOSIC) method for enzymatic DNA oligonucleotide production. Using this method, we amplify oligonucleotides from clonal templates followed by digestion of a cutter-hairpin, resulting in pools of monoclonal oligonucleotides with precisely controlled relative stoichiometric ratios. We present data where MOSIC oligonucleotides, 14–378 nt long, were prepared either by in vitro rolling-circle amplification, or by amplification in Escherichia coli in the form of phagemid DNA. The formation of a DNA crystal and folding of DNA nanostructures confirmed the scalability, purity and stoichiometry of the produced oligonucleotides. PMID:23727986

  11. Localisation of metastatic carcinoma by a radiolabelled monoclonal antibody

    Energy Technology Data Exchange (ETDEWEB)

    Smedley, H M; Ritson, A; Wraight, P; Sikora, K [Addenbrooke' s Hospital, Cambridge (UK); Hinchingbrooke Hospital, Huntingdon (UK)); Finan, P [St. James Hospital, Leeds (UK); Lennox, E S; Takei, F [Medical Research Council, Cambridge (UK)

    1983-02-01

    Rat monoclonal antibodies were prepared by immunising rats with human colorectal carcinoma cell membranes and fusing splenic lymphocytes with a rat myeloma. Hybridoma supernatants were screened by binding assays on membranes prepared from colorectal carcinoma tissue. One hybridoma supernatant, containing a monoclonal antibody with high binding activity on malignant compared to normal colon sections, was grown in large quantities in serum-free medium. After ammonium sulphate precipitation the antibody was purified by ion-exchange chromatography and labelled with /sup 131/I. Radiolabelled antibody was administered i.v. to 27 patients with colonic and other tumours. Scintigrams were obtained at 48 h. Computerised subtraction of the blood pool image revealed localised areas of uptake corresponding with areas of known disease in 13/16 patients with colorectal carcinoma and 3/4 patients with breast cancer.

  12. Monoclonal antibodies: potential role in radiation therapy and oncology

    International Nuclear Information System (INIS)

    Order, S.E.

    1982-01-01

    Specificity, which is a hallmark of the immune system, will be used in radiation oncology in both diagnosis and therapy through the application of radiolabelled monoclonal and polyclonal antibodies. Antigenic specificities, antibody preparations, and the tumor as a target for radiolabelled antibody is reviewed. Several clinical situations, i.e. single tumor cell suspensions, intraperitoneal single cells and masses, and solid tumors are reviewed in regard to both immune antibody targeting and specific differences between tumors in these regions. The concentration of tumor associated antigens is introductory to radiolabelled antibodies in diagnosis. In the radiation therapy of solid tumors, data regarding tumor dose, tumor effective half-life, varied antibody preparations, and the use of radiolabelled antibody as a method of tumor implantation is discussed using antiferritin 131 I-IgG as a model in hepatoma. The theoretical applications of monoclonal antibody integrated in cancer therapy are then presented as a new goal for future development

  13. [Diagnosis of rabies infection in animals using monoclonal antibodies].

    Science.gov (United States)

    Akacem, O; Taril, A; Benelmouffok, A; Bemansour, A; Couillin, P; Brahimi, M; Benhassine, M

    1989-01-01

    Two monoclonal antibodies (M.A.), specific for viral nucleocapsid, the M.A. D-20 and the M.A. D-43 raised against a fixed strain of rabies virus (C.V.S. 11), have been tested in parallel with a standard antirabies serum (S.A.R.) in diagnosis of animal rabies virus infection. 44 brain imprints from animals which died from rabies were tested by indirect immunofluorescent technique with monoclonal antibodies. Constant correlation has been found between the M.A. D-43 and the S.A.R. in the diagnosis of animal rabies virus infection in all cases studied. For M.A. D-20, concordance of results with S.A.R. was found only in limited number of cases.

  14. Development of radiolabelling techniques of anti-CEA monoclonal antibody

    International Nuclear Information System (INIS)

    Castiglia, S.G. de

    1998-01-01

    The purpose of this work was to label monoclonal and polyclonal antibodies with 99 Tc m such as the ior-CEA-1 antibody and polyclonal IgG using a direct method, to check the radiochemical and biological behavior of labelled products, to prepare it under sterile and apyrogenic conditions as a lyophilized kit and to employ it in clinical trials. In addition, a photoactivation method was used to label polyclonal IgG with 99 Tc m and to compare with the established method using mercaptoethanol (2-ME) as the reducing agent. Finally polyclonal IgG was labelled using an indirect method in which a chelator was covalently attached to the protein and the 99 Tc m added as glucoheptonate complex. The properties of 99 Tc m when labelled with monoclonal and polyclonal antibodies by different methods were assessed by in vitro and in vivo studies

  15. Boronated monoclonal antibody conjugates for neutron capture therapy

    International Nuclear Information System (INIS)

    Borg, D.C.; Elmore, J.J. Jr.; Ferrone, S.

    1986-01-01

    This paper describes the effectiveness of 10 B-labeled monoclonal antibodies against Colo-38 human melanoma in vitro. The authors obtained high boron to antibody ratios while maintaining antibody activity by using dextran intermediate carriers to link 10 B to the antibody. They developed a double cell quasi-competitive binding bioassay to minimize the effects of nonspecific binding of boronated complexes to cells. 1 fig., 2 tabs

  16. Human monoclonal antibodies: the residual challenge of antibody immunogenicity.

    Science.gov (United States)

    Waldmann, Herman

    2014-01-01

    One of the major reasons for seeking human monoclonal antibodies has been to eliminate immunogenicity seen with rodent antibodies. Thus far, there has yet been no approach which absolutely abolishes that risk for cell-binding antibodies. In this short article, I draw attention to classical work which shows that monomeric immunoglobulins are intrinsically tolerogenic if they can be prevented from creating aggregates or immune complexes. Based on these classical studies two approaches for active tolerization to therapeutic antibodies are described.

  17. Positron emission tomographic imaging of tumors using monoclonal antibodies

    Energy Technology Data Exchange (ETDEWEB)

    Zalutsky, M.R.

    1992-08-01

    This research project is developing methods for utilizing positron emission tomography (PET) to increase the clinical potential of radiolabeled monoclonal antibodies (MAbs). This report describes the development of methods for labeling MAbs and their fragments with positron-emitting halogen nuclides, fluorine-18 and iodine-124. These nulides were selected because of the widespread availability of F-18 and because of our extensive experience in the development of new protein radiohalogenation methods.

  18. Monoclonal antibodies to Nocardia asteroides and Nocardia brasiliensis antigens.

    OpenAIRE

    Jiménez, T; Díaz, A M; Zlotnik, H

    1990-01-01

    Nocardia asteroides and Nocardia brasiliensis whole-cell extracts were used as antigens to generate monoclonal antibodies (MAbs). Six stable hybrid cell lines secreting anti-Nocardia spp. MAbs were obtained. These were characterized by enzyme-linked immunosorbent assay, Western blot (immunoblot), and immunofluorescence assay. Although all the MAbs exhibited different degrees of cross-reactivity with N. asteroides and N. brasiliensis antigens as well as with culture-filtrate antigens from Myco...

  19. Microdosimetry of monoclonal antibodies labeled with alpha emitters

    International Nuclear Information System (INIS)

    Fisher, D.R.

    1986-01-01

    The recent discovery of new techniques for the production of monoclonal antibodies (MoAB) has opened up a number of potential new applications in cancer diagnosis and therapy. Monoclonal antibodies labeled with alpha-emitting radionuclides promise to be particularly effective therapeutic agents due to the efficient cell killing ability of highly ionizing, short-range alpha particle tracks localized at specific antigen sites within the tumor mass. For a radioimmunotherapy treatment plan to be effective, one must be able to estimate the absorbed radiation dose to both tumor cells and normal tissues in the body. However, conventional methods used in nuclear medicine for estimating absorbed doses and specific absorbed fractions for radiopharmaceuticals do not apply to alpha emitters owing to their short range and the large variations in the local distribution of energy at the cellular level that result. Microdosimetric techniques developed for assessment of the radiological effects of internally deposited transuranic radionuclides take into account the statistical aspects of alpha particle track structure, energy distribution patterns, and radionuclide distribution within tissues, and provide a means for determining the number and frequency of cells irradiated, the probability densities in specific energy, and the average dose delivered to cells of interest. These techniques can be applied to the study of radiation absorbed dose from alpha-labeled monoclonal antibodies. 16 references, 6 figures

  20. Library of monoclonal antibodies against brush border membrane epithelial antigens

    International Nuclear Information System (INIS)

    Behar, M.; Katz, A.; Silverman, M.

    1986-01-01

    A purified fraction of proximal tubule brush border membranes (BBM) was prepared from dog kidney and used to immunize mice. The standard technique of hybridoma production was followed as described by Kohler and Milstein. Production of antibodies was detected by indirect immunofluorescence on dog kidney slices and by immunodot against the purified fraction on nitrocellulose. Five hybrids exhibited anti BBM activity. These were cloned twice and yielded stable cell lines producing IgG type monoclonal antibodies against BBM. They were designated A 1 , C 7 , D 3 , D 7 and H 4 . As a family these five monoclonals have broad tissue specificity, i.e. positive staining of the surface mucosa of intestinal kidney proximal tubules. D 3 exhibits even broader specificity for epithelium reacting with bile canaliculi and choroid plexus. The authors have verified that at least 4/5 antibodies are directed against BBM protein as revealed by immunoprecipitation of solubilized BBM and detected by Coomassie blue staining or autoradiography of lactoperoxidase labelled BBM. Most interestingly all antibodies bind to the surface of LL CPK 1 cells, a continuous pig kidney cell line of undefined origin but exhibiting many characteristics of proximal tubule cells. The library of monoclonal antibodies obtained provide important probes with which to study membrane biogenesis and polarization in epithelial cells

  1. Recent Advances in Monoclonal Antibody Therapies for Multiple Sclerosis

    Science.gov (United States)

    Stavropoulos, Nikolaos; Wittenberg, Nathan J.; Dasari, Harika; Abdelrahim, Murtada A.; Henley, John R.; Oh, Sang-Hyun; Warrington, Arthur E.; Rodriguez, Moses

    2016-01-01

    Introduction Multiple sclerosis (MS) is the most common chronic inflammatory, demyelinating disease of the CNS and results in neurological disability. Existing immunomodulatory and immunosuppressive approaches lower the number of relapses but do not cure or reverse existing deficits nor improve long-term disability in MS patients. Areas Covered Monogenic antibodies were described as treatment options for MS, however the immunogenicity of mouse antibodies hampered the efficacy of potential therapeutics in humans. Availability of improved antibody production technologies resulted in a paradigm shift in MS treatment strategies. In this review, an overview of immunotherapies for MS that use conventional monoclonal antibodies reactive to immune system and their properties and mechanisms of action will be discussed, including recent advances in MS therapeutics and highlight natural autoantibodies (NAbs) that directly target CNS cells. Expert Opinion Recent challenges for MS therapy are the identification of relevant molecular and cellular targets, time frame of treatment, and antibody toxicity profiles to identify safe treatment options for MS patients. The application of monoclonal antibody therapies with better biological efficacy associated with minimum side effects possesses huge clinical potential. Advances in monoclonal antibody technologies that directly target cells of nervous system may promote the CNS regeneration field from bench to bedside. PMID:26914737

  2. Improving food and agricultural production. Thailand. Application on monoclonal antibodies for progesterone measurement

    International Nuclear Information System (INIS)

    Butcher, G.W.

    1991-01-01

    The duties of the mission were to provide instructions on the maintenance of hybridoma cell lines and their culture and the harvesting of monoclonal antibodies; to assist the counterparts in Thailand to develop work plans for the use of monoclonal antibodies in radioimmunoassay measurements of progesterone; and to assess the need for and feasibility of establishing a laboratory for producing monoclonal antibodies directed against progesterone. The report contains a summary of the activities performed in fulfillment of these duties

  3. Cuban Monoclonal Antibodies for Radioimmunodiagnosis and Radioimmunotherapy of Cancer Diseases

    International Nuclear Information System (INIS)

    Casaco, A.

    2009-01-01

    The Centre of Molecular Immunology produces monoclonal antibodies for treating cancer diseases. We are mainly focus on two target systems; one is the epidermal growth factor receptor (EGF-R) because there is a tremendous relationship between the EGF/EGF-R system and several human tumours such as lung, head and neck, ovarian breast and brain cancers; the second one is the ganglioside system, the relevance of certain gangliosides in tumour growth and metastatic dissemination has been well documented, GM3(NeuGc) ganglioside is particularly interesting due to its restrictive expression in normal human tissues. Nimotuzumab (h-R3) is a humanized monoclonal antibody (mAb) that was obtained by complementarity-determining regions grafting of a murine mAb (ior egf/r3) to a human framework having remarkable antiproliferative, pro-apoptotic, and antiangiogenic effects. A Phase I clinical trial was performed to evaluate the toxicity and clinical effect of an intracavitary (intracerebral) administration of a single dose of nimotuzumab (h-R3) labelled with increasing doses of 188Re. All patients bearing astrocytomas grade III/IV should be treated previously with conventional therapies and have an EGF-R overexpression in the tumour, demonstrated by immunohistochemical study. Maximal tolerated dose was 3 mg of the h-R3 labelled with 10 mCi of 188 Re. The radioimmunoconjugate showed a high retention in the surgical created resection cavity and the brain adjacent tissues with a mean value of 85.5% of the injected dose one hour post-administration. This radioimmunoconjugate may be relatively safe and a promising therapeutic approach for treating high grade gliomas. GM3(NeuGc) ganglioside is particularly interesting due to its restrictive expression in normal human tissues according to immunohistochemical studies, using either polyclonal or monoclonal antibodies. But both immunohistochemical and biochemical methods have strongly suggested its over-expression in human breast and colon

  4. Monoclonal antibodies directed to E1 glycoprotein of rubella virus

    International Nuclear Information System (INIS)

    Umino, Y.; Sato, A.; Katow, S.; Matsuno, T.; Sugiura, A.

    1985-01-01

    We have prepared four monoclonal antibodies to rubella virus E1 glycoprotein. Three nonoverlapping antigenic sites were delineated on E1 protein by competitive binding assays. Antibodies binding to one site were characterized by high hemagglutination inhibition (HI) titer but poor neutralizing activity. The addition of antiglobulin conferred neutralizing activity. Antibodies directed to two other antigenic sites had modest hemolysis inhibition but little or no HI and neutralizing activities. The addition of antiglobulin markedly augmented HI activity but had little effect on neutralizing activity. Epitopes defined by three antibodies were conserved among four rubella virus strains examined. (Author)

  5. New monoclonal antibodies to rat testicular antigen, TEC-21

    Czech Academy of Sciences Publication Activity Database

    Hálová, Ivana; Dráberová, Lubica; Dráber, Petr

    2001-01-01

    Roč. 47, č. 5 (2001), s. 180-182 ISSN 0015-5500 R&D Projects: GA ČR GV312/96/K205; GA ČR GA204/00/0204; GA ČR GA310/00/0205; GA AV ČR IAA5052005; GA AV ČR IAA7052006; GA MŠk LN00A026 Keywords : Monoclonal antibody * lipid raft * testicular cells Subject RIV: EC - Immunology Impact factor: 0.519, year: 2001

  6. New monoclonal antibodies to rat testicular antigen, TEC-21

    Czech Academy of Sciences Publication Activity Database

    Hálová, Ivana; Dráberová, Lubica; Dráber, Petr

    2001-01-01

    Roč. 47, č. 5 (2001), s. 180-182 ISSN 0015-5500 R&D Projects: GA ČR GV312/96/K205; GA ČR GA204/00/0204; GA ČR GA310/00/0205; GA AV ČR IAA5052005; GA AV ČR IAA7052006; GA MŠk LN00A026 Institutional research plan: CEZ:AV0Z5052915 Keywords : monoclonal antibody * GPI-anchored * testicular antigen Subject RIV: EB - Genetics ; Molecular Biology Impact factor: 0.519, year: 2001

  7. Monoclonal Antibody Shows Promise as Potential Therapeutic for MERS | Poster

    Science.gov (United States)

    A monoclonal antibody has proven effective in preventing Middle Eastern Respiratory Syndrome (MERS) in lab animals, suggesting further development as a potential intervention for the deadly disease in humans, according to new research. MERS is a newly emerged coronavirus first detected in humans in 2012. Most cases have occurred in the Middle East, but the disease has appeared elsewhere. In all, MERS has infected more than 1,700 individuals and killed more than 600, according to the World Health Organization. No vaccines or antiviral therapies currently exist. Several candidate vaccines are being developed, and some have been tested in animal models, a prerequisite to human clinical trials.

  8. Structural identification and characterization of monoclonal antibodies to rat angiotensinogen

    International Nuclear Information System (INIS)

    Nagel, M.

    1984-01-01

    Balb/c mice were immunised in vivo using angiotensinogen obtained from rats. In order to confirm that an immunoreaction had taken place, the concentration of specific antibodies was determined in selected sera on the basis of a radioimmunological method. In view of the fact that the affinity of the antibodies of the three monoclonal lines isolated here was calculated to be in the order of 10 7 l/mol it appears that their main field of use in affinity chromatography would be the purification of angiotensinogen from rats. (orig./MG) [de

  9. Enhanced monoclonal antibody production by gradual increase of osmotic pressure

    OpenAIRE

    Lin, Jianqiang; Takagi, Mutsumi; Qu, Yinbo; Gao, Peiji; Yoshida, Toshiomi

    1999-01-01

    The time length required for the adaptation of AFP-27 hybridoma cells to high osmotic pressure and the effect of a gradual increase of osmotic pressure on monoclonal antibody production were investigated. When the cells were subjected to an increase of osmotic pressure from 300 mOsmol kg-1 to 366 mOsmol kg- 1, the intracellular content of osmoprotective free amino acids reached a maximum level 6 h after the osmotic pressure was increased to 366 mOsmol kg-1. The same time period of 6 h incubat...

  10. A simple method for affinity purification of radiolabeled monoclonal antibodies

    Energy Technology Data Exchange (ETDEWEB)

    Juweid, M; Sato, J; Paik, C; Onay-Basaran, S; Weinstein, J N; Neumann, R D [National Cancer Inst., Bethesda, MD (United States)

    1993-04-01

    A simple method is described for affinity purification of radiolabeled antibodies using glutaraldehyde-fixed tumor target cells. The cell-bound antibody fraction is removed from the cells by an acid wash and then immediately subjected to buffer-exchange chromatography. The method was applied to the D3 murine monoclonal antibody which binds to a 290 kDa antigen on the surface of Line 10 guinea pig carcinoma cells. No alteration in the molecular size profile was detected after acid washing. Purification resulted in a significant increase in immunoreactivity by an average of 14 [+-] 47% (SD; range 4-30%). (author).

  11. Corneal Structural Changes in Nonneoplastic and Neoplastic Monoclonal Gammopathies.

    Science.gov (United States)

    Aragona, Pasquale; Allegra, Alessandro; Postorino, Elisa Imelde; Rania, Laura; Innao, Vanessa; Wylegala, Edward; Nowinska, Anna; Ieni, Antonio; Pisani, Antonina; Musolino, Caterina; Puzzolo, Domenico; Micali, Antonio

    2016-05-01

    To investigate corneal confocal microscopic changes in nonneoplastic and neoplastic monoclonal gammopathies. Three groups of subjects were considered: group 1, twenty normal subjects; group 2, fifteen patients with monoclonal gammopathy of undetermined significance (MGUS); group 3, eight patients with smoldering multiple myeloma and eight patients with untreated multiple myeloma. After hematologic diagnosis, patients underwent ophthalmologic exam and in vivo confocal microscopic study. The statistical analysis was performed using ANOVA and Student-Newman-Keuls tests and receiver operating characteristic (ROC) curve analysis. Epithelial cells of gammopathic patients showed significantly higher reflectivity than controls, demonstrated by optical density (P < 0.001). Subbasal nerve density, branching, and beading were significantly altered in gammopathic patients (P = 0.01, P = 0.02, P = 0.02, respectively). The number of keratocytes was significantly reduced in neoplastic patients (P < 0.001 versus both normal and MGUS) in the anterior, medium, and posterior stroma. The ROC curve analysis showed good sensitivity and specificity for this parameter. Group 2 and 3 keratocytes showed higher nuclear and cytoplasmatic reflectivity in the medium and posterior stroma. Endothelial cells were not affected. Patients with neoplastic gammopathies showed peculiar alterations of the keratocyte number, which appeared significantly reduced. A follow-up with corneal confocal microscopy of patients with MGUS is suggested as a useful tool to identify peripheral tissue alterations linked to possible neoplastic disease development.

  12. Monoclonal anti-elastin antibody labelled with technetium-99m

    International Nuclear Information System (INIS)

    Oliveira, Marcia B.N. de; Silva, Claudia R. da; Araujo, Adriano C. de; Bernardo Filho, Mario; Porto, Luis Cristovao M.S.; Gutfilen, Bianca; Souza, J.E.Q.; Frier, Malcolm

    1999-01-01

    Technetium-99m ( 99m Tc) is widely employed in nuclear medicine due to its desirable physical, chemical and biological properties. Moreover, it is easily available and normally is inexpensive. A reducing agent is necessary to label cells and molecules with 99m Tc and stannous chloride (Sn C L 2 ) is usually employed. Elastin is the functional protein component of the elastic fiber and it is related with some diseases such as arteriosclerosis, pulmonary emphysema and others. The present study refers to the preparation of the 99m Tc labeled monoclonal anti-elastin antibody. The monoclonal antibody was incubated with an excess of 2-iminothiolane. The free thiol groups created, were capable of binding with the reduced technetium. Labeling was an exchange reaction with 99m Tc-glucoheptonate. The labeled preparation was left at 4 deg C for one hour. Then, it was passed through a Sephadex G50 column. Various fractions were collected and counted. A peak corresponding to the radiolabeled antibody was obtained. Stability studies of the labelled anti-elastin were performed at 0,3 6, 24 hours, at both 4 deg C or room temperature. The biodistribution pattern of the 99m Tc-anti-elastin was studied in healthy male Swiss mice. The immunoreactivity was also determined. An useful labeled-anti-elastin was obtained to future immunoscintigraphic investigations. (author)

  13. [Batch release of immunoglobulin and monoclonal antibody products].

    Science.gov (United States)

    Gross, S

    2014-10-01

    The Paul-Ehrlich Institute (PEI) is an independent institution of the Federal Republic of Germany responsible for performing official experimental batch testing of sera. The institute decides about the release of each batch and performs experimental research in the field. The experimental quality control ensures the potency of the product and also the absence of harmful impurities. For release of an immunoglobulin batch the marketing authorization holder has to submit the documentation of the manufacture and the results of quality control measures together with samples of the batch to the PEI. Experimental testing is performed according to the approved specifications regarding the efficacy and safety. Since implementation of the 15th German drug law amendment, the source of antibody is not defined anymore. According to § 32 German drug law, all batches of sera need to be released by an official control laboratory. Sera are medicinal products, which contain antibodies, antibody fragments or fusion proteins with a functional antibody portion. Therefore, all batches of monoclonal antibodies and derivatives must also be released by the PEI and the marketing authorization holder has to submit a batch release application. Under certain circumstances a waiver for certain products can be issued with regard to batch release. The conditions for such a waiver apply to the majority of monoclonal antibodies.

  14. Imaging thrombus with radiolabelled monoclonal antibody to platelets

    Energy Technology Data Exchange (ETDEWEB)

    Peters, A.M.; Lavender, J.P.; Needham, S.G.; Loutfi, I.; Snook, D.; Epenetos, A.A.; Lumley, P.; Keery, R.J.; Hogg, N.

    1986-12-13

    A study was conducted evaluating a method of imaging thrombus with platelets radiolabelled with a /sup 111/In labelled monoclonal antibody, P256, directed to the platelet surface glycoprotein complex IIb/IIIa. when the number of receptors occupied by P256 was less than 3% of the total available on the platelet surface, platelet function was undisturbed. P256 was radiolabelled with /sup 111/In using diethylenetriaminepenta-acetic acid, which achieved a specific activity of 185 MBq (5 mCi)/mg. No impairment of immunoreactivity was detected at this specific activity. Platelets were labelled with radiolabelled monoclonal antibody in vitro in two patients at a receptor occupancy of 6% and in vivo in six patients at a receptor occupancy of 1%. In vivo recovery and biodistribution kinetics suggested that after in vitro labelling platelets were minimally activated. The /sup 111/In kinetics recorded after intravenous P256 suggested rapid and efficient radiolabelling of platelets and gave no indication of platelet activation. Of the six patients who received intravenous P256, three had documented thrombus, two of whom gave positive results on P256 platelet scintigraphy. The third had chronic deep venous thrombosis and was scintigraphically negative.

  15. Generation of monoclonal antibodies against highly conserved antigens.

    Directory of Open Access Journals (Sweden)

    Hongzhe Zhou

    Full Text Available BACKGROUND: Therapeutic antibody development is one of the fastest growing areas of the pharmaceutical industry. Generating high-quality monoclonal antibodies against a given therapeutic target is very crucial for the success of the drug development. However, due to immune tolerance, some proteins that are highly conserved between mice and humans are not very immunogenic in mice, making it difficult to generate antibodies using a conventional approach. METHODOLOGY/PRINCIPAL FINDINGS: In this report, the impaired immune tolerance of NZB/W mice was exploited to generate monoclonal antibodies against highly conserved or self-antigens. Using two highly conserved human antigens (MIF and HMGB1 and one mouse self-antigen (TNF-alpha as examples, we demonstrate here that multiple clones of high affinity, highly specific antibodies with desired biological activities can be generated, using the NZB/W mouse as the immunization host and a T cell-specific tag fused to a recombinant antigen to stimulate the immune system. CONCLUSIONS/SIGNIFICANCE: We developed an efficient and universal method for generating surrogate or therapeutic antibodies against "difficult antigens" to facilitate the development of therapeutic antibodies.

  16. Monoclonal antibodies specific to heat-treated porcine blood.

    Science.gov (United States)

    Raja Nhari, Raja Mohd Hafidz; Hamid, Muhajir; Rasli, Nurmunirah Mohamad; Omar, Abdul Rahman; El Sheikha, Aly Farag; Mustafa, Shuhaimi

    2016-05-01

    Porcine blood is potentially being utilized in food as a binder, gelling agent, emulsifier or colorant. However, for certain communities, the usage of animal blood in food is strictly prohibited owing to religious concerns and health reasons. This study reports the development of monoclonal antibodies (MAbs) against heat-treated soluble proteins (HSPs) of autoclaved porcine blood; characterization of MAbs against blood, non-blood and plasma from different animal species using qualitative indirect non-competitive enzyme-linked immunosorbent assay (ELISA); and immunoblotting of antigenic components in HSPs of porcine blood. Fifteen MAbs are specific to heat-treated and raw porcine blood and not cross-reacted with other animal blood and non-blood proteins (meat and non-meat). Twelve MAbs are specific to porcine plasma, while three MAbs specific to porcine plasma are cross-reacted with chicken plasma. Immunoblotting revealed antigenic protein bands (∼60, ∼85-100 and ∼250 kDa) in porcine blood and plasma recognized by the MAbs. Selection of MAbs that recognized 60 kDa HSPs of porcine blood and plasma as novel monoclonal antibodies would be useful for detection of porcine plasma in processed food using the immunoassay method. © 2015 Society of Chemical Industry. © 2015 Society of Chemical Industry.

  17. Generation and characterization of monoclonal antibodies against Giardia muris trophozoites.

    Science.gov (United States)

    Heyworth, M F; Ho, K E; Pappo, J

    1989-11-01

    Mouse monoclonal antibodies (mAb) were produced against Giardia muris trophozoite surface antigens. To generate B-cell hybridomas, P3/NS1/1-Ag4-1 myeloma cells were fused with splenic lymphocytes from BALB/c mice that had been immunized parenterally with G. muris trophozoites. Hybridoma culture supernatants were screened for mAb by flow cytometry of G. muris trophozoites incubated with culture supernatant followed by fluorescein-conjugated anti-mouse IgG and IgM. Flow cytometry showed three types of trophozoite staining by mAb: (i) bright staining of greater than 90% of trophozoites, with aggregation of the organisms; (ii) bright staining of approximately 90% of trophozoites, with little or no aggregation; (iii) dull staining of approximately 20% of trophozoites, without aggregation. Western blotting of mAb on G. muris trophozoite antigens separated by polyacrylamide gel electrophoresis showed that a mAb exhibiting the third of these flow cytometry staining patterns recognized trophozoite antigens of MW approximately 31,000 and 35,000. Immunoprecipitation studies indicated that the same mAb specifically precipitated two 125I-labelled trophozoite surface antigens of MW approximately 30,000. Monoclonal antibodies generated in this study may facilitate the purification and biochemical characterization of trophozoite antigens that are targets for protective intestinal antibody in G. muris-infected mice.

  18. New tools for immunochemistry: internally labelled monoclonal antibodies

    International Nuclear Information System (INIS)

    Galfre, G.; Cuello, A.C.

    1981-01-01

    Labelled antibodies are routinely used in a wide variety of immunochemical methods. Over the years several labelling techniques have been developed and the discussion of some of them forms a substantial part of this course. Common to all the procedures is the need to purify the antibodies. The labelling itself consists of coupling the antibodies to a ''label'' molecule by means of a chemical reaction. Preparation in vitro of monoclonal antibodies offers the unique possibility to internally label them. Although this is restricted to radiolabelling, and the specific activity achieved is limited, the procedure is extremely simple, does not require purification prior to labelling and chemical manipulation is not necessary as the antibodies themselves are synthesized from radioactive amino acids. Moreover, different labels can be used ( 14 C, 35 S, 3 H) which have a much longer half-life than 125 I. The choice of labelled amino acid precurors and labelling procedure is discussed. The uses of internally-labelled monoclonal antibodies are indicated. (Auth.)

  19. Desensitization for Drug Hypersensitivity to Chemotherapy and Monoclonal Antibodies.

    Science.gov (United States)

    Bonamichi-Santos, Rafael; Castells, Mariana

    2016-01-01

    Chemotherapies drugs and monoclonal antibodies are key components of the treatment of cancer patients and patients with chronic inflammatory conditions to provide increase in life expectancy and quality of life. Their increased use has lead to an increase in drugs hypersensitivity reactions (DHR) worldwide. DHR to those agents prevented their use and promoted the use of second line therapies to protect patients' hypersensitive reactions and anaphylaxis. Second line medications may not fully address the patients' medical condition and it is desirable to keep patients on first line therapy. Drug hypersensitivity symptoms can range from mild cutaneous reactions to life-threatening anaphylaxis. Rapid drug desensitization (RDD) is a novel approach to the management of drug hypersensitivity reactions which are IgE and non-IgE mediated. Through the diferent desensitization protocols patients can receive the full dose of the medications that they have presented a hypersensitive reaction and been protected against anaphylaxis. This review looks at the current literature on hypersensitivity reactions (HSR) to chemotherapy drugs and monoclonal antibodies and the potential use of RDD for their management. Copyright© Bentham Science Publishers; For any queries, please email at epub@benthamscience.org.

  20. Monoclonal Antibody Production against Human Spermatozoal Surface Antigens

    Directory of Open Access Journals (Sweden)

    M Jedi-Tehrani

    2005-10-01

    Full Text Available Introduction: As monoclonal antibodies are potential tools for characterization of soluble or cellular surface antigens, use of these proteins has always been considered in infertility and reproduction research. Therefore, in this study, monoclonal antibodies against human sperm surface antigens were produced. Material and Methods: To produce specific clones against human sperm surface antigens, proteins were extracted using solubilization methods. Balb/c mice were immunized intraperitoneally with the proteins using complete Freund’s adjuvant in the first injection and incomplete Adjuvant in the following booster injections. Hybridoma cells producing ASA were cloned by limiting dilution. Results: Five stable ASA producing hybridoma clones were achieved and their antibody isotypes were determined by ELISA. All the isotypes were of IgG class. Their cross reactivity with rat and mice spermatozoa was examined but they did not have any cross reactivity. Conclusion: The produced antibodies can be used in further studies to characterize and evaluate each of the antigens present on human sperm surface and determining their role in fertilization.

  1. Monkey-derived monoclonal antibodies against Plasmodium falciparum

    International Nuclear Information System (INIS)

    Stanley, H.A.; Reese, R.T.

    1985-01-01

    A system has been developed that allows efficient production of monkey monoclonal antibodies from owl monkeys. Splenocytes or peripheral blood lymphocytes from monkeys immune to the human malarial parasite, Plasmodium falciparum, were fused with P3X63 Ag8.653 mouse myelomas. The resulting hybridomas were screened by an indirect fluorescent antibody test for the production of monkey monoclonal antibodies (mAb) reactive with P. falciparum. Most of the mAb reacted with the P. falciparum merozoites and immunoprecipitated a parasite-derived glycoprotein having a relative molecular weight of 185,000. These mAb gave a minimum of five different immunoprecipitation patterns, thus demonstrating that a large number of polypeptides obtained when parasitized erythrocytes are solubilized share epitopes with this large glycoprotein. In addition, mAb were obtained that reacted with antigens associated with the infected erythrocyte membrane. One of these mAb bound a M/sub r/ 95,000 antigen. Radioimmunoprecipitation assays using 125 T-antibodies were done

  2. Monoclonal antibody studies in B(non-T)-cell malignancies.

    Science.gov (United States)

    Shimoyama, M; Minato, K; Tobinai, K; Nagai, M; Hirose, M

    1983-09-01

    Tumor cells suspensions prepared from 129 B- or non-T cell malignancies were investigated with a panel of 10 monoclonal antibodies and conventional surface marker techniques. Surface immunoglobulin (sIg) and B1 antigen proved to be the most useful markers for B-cell lineage. Six major subtypes of acute lymphoblastic leukemia (ALL) of non-T cell nature are now recognized by these immunological techniques, including null-ALL, Ia-ALL, lymphoid stem cell ALL, pre-pre-B ALL, pre-B ALL and B-ALL. In cases of chronic leukemias and lymphomas of non-T cell nature, 80% of the tumor was defined by sIg and 88% by B1 antigen as definitely of B-cell lineage. The clonal character was also defined in 68% of the tumor on the basis of the detection of predominant single light chain in sIg. Ia-like antigen was detected in almost all cases (96%). Leukemic cells from all cases of chronic lymphocytic leukemia (CLL), chronic lymphosarcoma cell leukemia (CLsCL) and hairy cell leukemia (HCL) reacted with OKIa1 and anti-B1, and leukemic cells from most of them with anti-pan T monoclonal antibody (10.2). In more than half of CLL and CLsCL, leukemic cells were reactive with J5, OKM1, 9.6 and OKT8, but not with OKT3, OKT4 and OKT6. HCL cells had almost the same reactivity with these monoclonal antibodies as CLL and CLsCL cells except that J5 remained unreactive. These results indicated that Japanese CLL, CLsCL and HCL were different from Western ones at least with respect to surface marker characteristics. In cases of lymphomas, heavy chains of sIg were expressed in polyclonal fashion, especially in follicular lymphoma and diffuse lymphomas of medium sized cell type and large cell type, indicating that lymphomas of these types may originate from follicular center cells of the heavy chain switching stage. Anti-T monoclonals were also reactive with lymphoma cells. In about half of follicular lymphomas and diffuse lymphomas of the medium sized cell type, lymphoma cells reacted with 10.2, and less

  3. Synthetic methyl hexagalacturonate hapten inhibitors of antihomogalacturonan monoclonal antibodies LM7, JIM5 and JIM7

    DEFF Research Database (Denmark)

    Clausen, Mads Hartvig; Willats, William George Tycho; Knox, J. Paul

    2003-01-01

    A range of synthetic methyl hexagalacturonates were used as potential hapten inhibitors in competitive-inhibition enzyme-linked immunosorbent assays (ELISAs) with anti-homogalacturonan monoclonal antibodies LM7, JIM5 and JIM7. The selective inhibition of these antibodies by different haptens...... provides insight into the structures of the partially methyl-esterified pectin epitopes of these widely used monoclonal antibodies....

  4. The classification of Sejroe group serovars of Leptospira interrogans with monoclonal antibodies

    NARCIS (Netherlands)

    Terpstra, W. J.; Korver, H.; van Leeuwen, J.; Klatser, P. R.; Kolk, A. H.

    1985-01-01

    Using the hybridoma technique we produced monoclonal antibodies to serovars of Leptospira interrogans. We focussed on serovar hardjo which is an important pathogen for humans and animals, and on other serovars of the Sejroe group. With combinations of monoclonals, characteristic patterns of

  5. An ELISA-inhibition test using monoclonal antibody for the serology of leprosy

    NARCIS (Netherlands)

    Klatser, P. R.; de Wit, M. Y.; Kolk, A. H.

    1985-01-01

    In this study a mouse monoclonal antibody (47-9) is described, which recognized an epitope on the 36 kD protein antigen of M. leprae. The monoclonal antibody showed specificity for M. leprae. An ELISA-inhibition test based on the competitive inhibition by antibodies from human test sera of the

  6. Homology of ab1 and ab3 monoclonal antibodies that neutralize Semliki Forest virus

    NARCIS (Netherlands)

    Fernandez, IM; Bos, NA; Harmsen, M; Verheul, AFM; Snippe, H; Kraaijeveld, CA

    2001-01-01

    A noninternal image monoclonal antiidiotypic antibody (ab2 mAb), designated 1,13A321, that had proved its efficacy as vaccine against infection with Semliki Forest virus (SFV) in BALB/c mice, was used as immunogen to generate a panel of SFV-neutralizing monoclonal anti-anti-idiotypic antibodies (ab3

  7. Magnetic resonance appearance of monoclonal gammopathies of unknown significance and multiple myeloma. The GRI Study Group.

    Science.gov (United States)

    Bellaïche, L; Laredo, J D; Lioté, F; Koeger, A C; Hamze, B; Ziza, J M; Pertuiset, E; Bardin, T; Tubiana, J M

    1997-11-01

    A prospective multicenter study. To evaluate the use of magnetic resonance imaging, in the differentiation between monoclonal gammopathies of unknown significance and multiple myeloma. Although multiple myeloma has been studied extensively with magnetic resonance imaging, to the authors' knowledge, no study has evaluated the clinical interest of magnetic resonance imaging in the differentiation between monoclonal gammopathies of unknown significance and multiple myeloma. The magnetic resonance examinations of the thoracolumbar spine in 24 patients with newly diagnosed monoclonal gammopathies of unknown significance were compared with those performed in 44 patients with newly diagnosed nontreated multiple myeloma. All findings on magnetic resonance examination performed in patients with monoclonal gammopathies of unknown significance were normal, whereas findings on 38 (86%) of the 44 magnetic resonance examinations performed in patients with multiple myeloma were abnormal. Magnetic resonance imaging can be considered as an additional diagnostic tool in differentiating between monoclonal gammopathies of unknown significance and multiple myeloma, which may be helpful when routine criteria are not sufficient. An abnormal finding on magnetic resonance examination in a patient with monoclonal gammopathies of unknown significance should suggest the diagnosis of multiple myeloma after other causes of marrow signal abnormalities are excluded. Magnetic resonance imaging also may be proposed in the long-term follow-up of monoclonal gammopathies of unknown significance when a new biologic or clinical event suggests the diagnosis of malignant monoclonal gammopathy.

  8. [Production of monoclonal antibodies against a wild strain of rabies virus].

    Science.gov (United States)

    Akacem, O; Benmansour, A; Coulon, P; Brahimi, M; Benhassine, M

    1992-01-01

    Production of monoclonal antibodies against a wild strain of rabies virus. Cell fusion of SP 2/O, a murine myeloma against a wild strain of rabies virus has originated five monoclonal antibodies (M.A.) specific for virus nucleocapsid , one M.A. specific for virus glycoprotein and one M.A. specific for a viral membrane protein.

  9. Use of commercially available rabbit monoclonal antibodies for immunofluorescence double staining

    DEFF Research Database (Denmark)

    Bzorek, M.; Stamp, I.M.; Frederiksen, L.

    2008-01-01

    Immunohistochemistry, that is, the use of polyclonal and monoclonal antibodies to detect cell and tissue antigens at a microscopical level is a powerful tool for both research and diagnostic purposes. Especially in the field of hematologic disease, there is often a need to detect several antigens...... synchronously, and we report here a fast and easy technique for demonstrating more than 1 antigen in 1 slide using immunofluorescence. We have used commercially available rabbit monoclonal antibodies (Cyclin D1, CD3, CD5, CD23, etc.) paired with mouse monoclonal antibodies (CD7, CD20, CD79a, Pax-5, etc.......) for double immunofluorescence labeling on paraffin-embedded tissue sections. Commercially available rabbit monoclonal antibodies in combination with mouse monoclonal antibodies proved useful in double immunofluorescence labeling on paraffin-embedded tissue, and all combinations used yielded excellent results...

  10. A rapid one-step radiometric assay for hepatitis B surface antigen utilising monoclonal antibodies

    International Nuclear Information System (INIS)

    Goodall, A.H.; Meek, F.L.; Waters, J.A.; Miescher, G.C.; Janossy, G.; Thomas, H.C.

    1982-01-01

    A two-site antigen assay for HBsAg has been developed that employs 3 monoclonal antibodies. The antibodies were selected for their high affinity and their particular epitope specificity to establish an assay with a sensitivity for the antigen comparable with that of a conventional assay with heterologous antisera. In addition, by selecting a monoclonal antibody for use as a tracer which does not compete for antigenic binding sites with the solid-phase monoclonal antibodies, it has been possible to perform a two-site assay in a single 1 h incubation step, achieving the same degree of sensitivity. This principle of using monoclonal antibodies in a one-step assay therefore gives advantages of speed and simplicity over assays using heterologous antisera and would be applicable to a variety of antigen assays for which appropriate monoclonal antibodies are available. (Auth.)

  11. The use of indium-111 platelet scintigraphy in man: comparisons with in vitro tests and in vivo platelet function--a five year experience

    International Nuclear Information System (INIS)

    Ezikowitz, M.D.; Ferri, P.; Pope, C.; Smith, E.O.; Snyder, E.L.

    1985-01-01

    In this paper, the authors present data collected from 540 patients between July 1978 and July 1983. They discuss briefly the method they employed for labeling platelets, emphasizing in vivo and in vitro markers of platelet function used for quality control of platelet preparation. They discuss the application of their technique for identification of mural left ventrical trombi, and review the disparity between in vivo and in vitro tests of platelet function. Then they deal with diagnosis of subacute bacterial endocarditis, deep veonus thrombosis, coronary trombi, left arterial masses, and the use of tomographic imaging. Finally they report changes in platelet function in stored platelets from normal volunteers

  12. Yttrium-90 and indium-111 labelling, receptor binding and biodistribution of [DOTA0,d-Phe1,Tyr3[octreotide, a promising somatostatin analogue for radionuclide therapy

    International Nuclear Information System (INIS)

    Jong, M. de; Bakker, W.H.; Krenning, E.P.; Breeman, W.A.P.; Pluijm, M.E. van der; Bernard, B.F.; Visser, T.J.; Jermann, E.; Behe, M.; Powell, P.; Maecke, H.R.

    1997-01-01

    In vitro octreotide receptor binding of [ 111 In-DOTA 0 ,d-Phe 1 ,Tyr 3 [octreotide ( 111 In-DOTATOC) and the in vivo metabolism of 90 Y- or 111 In-labelled DOTATOC were investigated in rats in comparison with [ 111 In-DTPA 0 [octreotide [ 111 In-DTPAOC). 111 In-DOTATOC was found to have an affinity similar to octreotide itself for the octreotide receptor in rat cerebral cortex microsomes. Twenty-four hours after injection of 90 Y- or 111 In-labelled DOTATOC, uptake of radioactivity in the octreotide receptor-expressing tissues pancreas, pituitary, adrenals and tumour was a factor of 2-6 that after injection of 111 In-DTPAOC. Uptake of labelled DOTATOC in pituitary, pancreas, adrenals and tumour was almost completely blocked by pretreatment with 0.5 mg unlabelled octreotide, indicating specific binding to the octreotide receptors. These findings strongly indicate that 90 Y-DOTATOC is a promising radiopharmaceutical for radiotherapy and that 111 In-DOTATOC is of potential value for diagnosis of patients with octreotide receptor-positive lesions, such as most neuroendocrine tumours. (orig.). With 3 figs., 2 tabs

  13. Effects of the Amino Acid Linkers on the Melanoma-Targeting and Pharmacokinetic Properties of Indium-111-labeled Lactam Bridge-Cyclized α-MSH Peptides

    Science.gov (United States)

    Guo, Haixun; Yang, Jianquan; Gallazzi, Fabio; Miao, Yubin

    2011-01-01

    The purpose of this study was to examine the profound effects of the amino acid linkers on the melanoma targeting and pharmacokinetic properties of novel 111In-labeled lactam bridge-cyclized DOTA-[X]-CycMSHhex {1,4,7,10-Tetraazacyclododecane-1,4,7,10-tetraacetic acid-[X]-c[Asp-His-dPhe-Arg-Trp-Lys]-CONH2, X=GlyGlyNle, GlyGluNle or NleGlyGlu} peptides. Methods Three novel DOTA-GGNle-CycMSHhex, DOTA-GENle-CycMSHhex and DOTA-NleGE-CycMSHhex peptides were designed and synthesized. The melanocortin-1 (MC1) receptor binding affinities of the peptides were determined in B16/F1 melanoma cells. The melanoma targeting and pharmacokinetic properties of 111In-DOTA-GGNle-CycMSHhex and 111In-DOTA-GENle-CycMSHhex were determined in B16/F1 melanoma-bearing C57 mice. Results DOTA-GGNle-CycMSHhex and DOTA-GENle-CycMSHhex displayed 2.1 and 11.5 nM MC1 receptor binding affinities, whereas DOTA-NleGE-CycMSHhex showed 873.4 nM MC1 receptor binding affinity. The introduction of the -GlyGly- linker maintained high melanoma uptake while decreased the renal and liver uptakes of 111In-DOTA-GlyGlyNle-CycMSHhex. The tumor uptake values of 111In-DOTA-GGNle-CycMSHhex were 19.05 ± 5.04 and 18.6 ± 3.56 % injected dose/gram (%ID/g) at 2 and 4 h post-injection. 111In-DOTA-GGNle-CycMSHhex exhibited 28, 32 and 42% less renal uptake values than 111In-DOTA-Nle-CycMSHhex we reported previously, and 61, 65 and 68% less liver uptake values than 111In-DOTA-Nle-CycMSHhex at 2, 4 and 24 h post-injection, respectively. Conclusion The amino acid linkers exhibited the profound effects on the melanoma targeting and pharmacokinetic properties of the 111In-labeled lactam bridge-cyclized α-MSH peptides. Introduction of the -GlyGly- linker maintained high melanoma uptake while reducing the renal and liver uptakes of 111In-DOTA-GlyGlyNle-CycMSHhex, highlighting its potential as an effective imaging probe for melanoma detection, as well as a therapeutic peptide for melanoma treatment when labeled with a therapeutic radionuclide. PMID:21421725

  14. Hepatobiliary delivery of polyaminopolycarboxylate chelates: Synthesis and characterization of a cholic acid conjugate of EDTA and biodistribution and imaging studies with its indium-111 chelate

    Energy Technology Data Exchange (ETDEWEB)

    Betebenner, D.A.; Carney, P.L.; Zimmer, A.M.; Kazikiewicz, J.M.; Bruecher, E.S.; Sherry, A.D.; Johnson, D.K. (Abbott Laboratories, Abbott Park, Illinois (USA))

    1991-03-01

    A conjugate in which the steroid nucleus of cholic acid was linked to EDTA via an 11-atom spacer was obtained by reacting the succinimidyl ester of cholic acid with the amine formed by reaction of a benzyl isothiocyanate derivative of EDTA with N-(tert-butoxycarbonyl)ethylenediamine and subsequent deprotection. Potentiometric titration studies with model complexes showed that the EDTA moiety retained the ability to form 1:1 chelates of high thermodynamic stability, although formation constants were some 3-4 log K units lower for complexes of the conjugate than for the analogous chelates with underivatized EDTA. A complex formed between the cholic acid-EDTA conjugate and 111InIII was clearly rapidly into the liver when injected iv into mice, with subsequent excretion from the liver into the gastrointestinal tract being complete within 1 h of injection. Radioscintigraphic imaging studies conducted in a rabbit given the 111In-labeled conjugate also showed early liver uptake followed by rapid clearance from the liver into the intestine, with good visualization of the gallbladder in images obtained at 20-25 min postinjection. It is concluded that conjugation to cholic acid provides a useful means for the hepatobiliary delivery of EDTA chelates that otherwise exhibit predominantly extracellular distribution and renal clearance.

  15. Hepatobiliary delivery of polyaminopolycarboxylate chelates: Synthesis and characterization of a cholic acid conjugate of EDTA and biodistribution and imaging studies with its indium-111 chelate

    International Nuclear Information System (INIS)

    Betebenner, D.A.; Carney, P.L.; Zimmer, A.M.; Kazikiewicz, J.M.; Bruecher, E.S.; Sherry, A.D.; Johnson, D.K.

    1991-01-01

    A conjugate in which the steroid nucleus of cholic acid was linked to EDTA via an 11-atom spacer was obtained by reacting the succinimidyl ester of cholic acid with the amine formed by reaction of a benzyl isothiocyanate derivative of EDTA with N-(tert-butoxycarbonyl)ethylenediamine and subsequent deprotection. Potentiometric titration studies with model complexes showed that the EDTA moiety retained the ability to form 1:1 chelates of high thermodynamic stability, although formation constants were some 3-4 log K units lower for complexes of the conjugate than for the analogous chelates with underivatized EDTA. A complex formed between the cholic acid-EDTA conjugate and 111InIII was clearly rapidly into the liver when injected iv into mice, with subsequent excretion from the liver into the gastrointestinal tract being complete within 1 h of injection. Radioscintigraphic imaging studies conducted in a rabbit given the 111In-labeled conjugate also showed early liver uptake followed by rapid clearance from the liver into the intestine, with good visualization of the gallbladder in images obtained at 20-25 min postinjection. It is concluded that conjugation to cholic acid provides a useful means for the hepatobiliary delivery of EDTA chelates that otherwise exhibit predominantly extracellular distribution and renal clearance

  16. Clinical usage of indium-111 labeled leukocyte scintigraphy and technetium-99m methylene diphosphonate scintigraphy in patients with total hip replacement

    International Nuclear Information System (INIS)

    Terauchi, Takashi; Uno, Kimiichi; Yuyama, Takuo; Seto, Kazuhiko; Arimizu, Noboru; Suguro, Tohru; Moriya, Hideshige; Uematsu, Sadao.

    1988-01-01

    Tc-99m methylene diphosphonate (MDP) scintigraphy and In-111 labeled leukocyte scintigraphy were done in 13 patients with total hip replacement in order to determine the presence of prosthetic infection. Tc-99m MDP scintigraphy was done in 11 patients (12 studies). In-111 labeled leukocyte scintigraphy was done in 13 patients (14 studies). Tc-99m MDP imaging showed diffuse accumulation of the radionuclide in all of the 3 infected lesions, but focal one in 5 of the 7 noninfected lesions with a specificity of 33.3 %, sensitivity of 100 %, overall accuracy of 50 %. In-111 labeled leukocyte normally accumulates in the spleen, the liver, and the bone marrow. Before insertion of a stemmed prosthesis, the local bone marrows were reamed out in all of our cases. Thus, no radioactive accumulation would be expected in the lesions with prosthesis unless infected. However, if the prosthesis is infected, increased uptake of In-111 would be seen as a result of the accumulation of leukocyte. In-111 labeled leukocyte imaging showed abnormal accumulation of In-111 in all of the 4 infected lesions and no accumulation in all of the 10 noninfected lesions with a specificity of 100 %, sensitivity of 100 %, overall accuracy of 100 %. We conclude that In-111 labeled leukocyte scintigraphy might be useful in evaluating prosthetic infection in a patient with total hip replacement. (author)

  17. Murine eosinophils labeled with indium-111 oxine: localization to delayed hypersensitivity reactions against a schistosomal antigen and to lymphokine in vivo

    International Nuclear Information System (INIS)

    Rand, T.H.; Clanton, J.A.; Runge, V.; English, D.; Colley, D.G.

    1983-01-01

    We have evaluated a method for quantitation of eosinophil migration to stimuli in vivo. Upon transfusion into normal syngeneic mice, 111In-labeled eosinophils had an intravascular half-life of 9.5 hr and distributed predominantly into spleen, bone marrow, and liver. In either Schistosoma mansoni-infected mice or recipients of lymphoid cells from infected mice, intradermal (ear pinna) injection of the schistosomal egg antigenic preparation (SEA) elicited time-dependent accumulation of 111In-labeled eosinophils detectable by either gamma scintillation counting of tissue samples or by nuclear medicine external imaging. Intradermal administration of a lymphokine fraction (containing eosinophil stimulation promoter activity) similarly caused accumulation of 111In-labeled eosinophils. Both reactions depended on the concentration of stimulus (SEA or lymphokine). 111In-labeled neutrophils or macrophages or 125I-albumin did not preferentially accumulate at the reactions examined to the extent found with 111In-labeled eosinophils, indicating that localization of label depends on an active process and is due to eosinophils rather than a contaminating cell type. The method was used to estimate how long eosinotactic lymphokine remained at dermal sites: 60% of initial activity was present 12 hr after injection. The model is discussed with regard to the role of lymphokines in hypersensitivity reactions with eosinophil involvement, such as the granulomatous response to S. mansoni eggs

  18. Labeling of peripheral blood polymorphonuclear leukocytes with indium-111: a new method for the quantitation of in-vivo accumulation of PMNLs in rabbit skin

    Energy Technology Data Exchange (ETDEWEB)

    Wahba, A.V.; Barnes, B.; Lazarus, G.S.

    1984-02-01

    A precise method for quantitation of polymorphonuclear leukocyte (PMNL) accumulation in skin in vivo, has been developed so that the proinflammatory effects of various agents can be compared. This method can also be used to evaluate the effect of therapeutic agents on PMNL accumulation in vivo. Rabbit PMNLs were purified from heparinized blood by dextran sedimentation, hypotonic lysis, and separation on Ficoll-Hypaque. The PMNLs were labeled with 3-5 microCi per 10(6) cells of /sup 111/In oxine and reinfused coincidentally with different concentrations of different chemotactic and proinflammatory materials injected intradermally into the back. In some experiments, varying concentrations of acetic acid were applied topically. Four to 18 hours later, the rabbits were sacrificed. Eight-millimeter punch biopsies were obtained from the injection sites and counted in a gamma counter. The number of PMNLs infiltrating the dermis was also quantitated in histologic sections. A significant correlation was found between the percent increase in radioactivity and the percent increase in PMNL accumulation morphologically. Dose-response curves were generated using such proinflammatory materials as formyl-methionyl-leucyl-phenylalanine, lipopolysaccharide, activated serum, trypsin, glycogen, and acetic acid. These curves were highly reproducible from animal to animal. Using this assay, we found that as little as 1 microgram of trypsin induced detectable PMNL accumulation. This is 2-3 logs more sensitive than injecting mice intraperitoneally with trypsin. Diisopropyl fluorophosphate-inactivation of trypsin inhibited PMNL accumulation. This sensitive and quantitative bioassay of PMNL accumulation permits evaluation of multiple agents in the same animal, which decreases animal to animal variation.

  19. Comparative orbital scintigraphy with technetium-99m-P829, indium-111-DOTA-Lanreotide and DOTA-Tyr3-octreotide in Graves disease

    International Nuclear Information System (INIS)

    Burggasser, G.; Hauff, W.; Thaler, A.; Hurtl, I.; Greifeneder, M.; Virgolini, I.; Traub, T.; Dudczak, R.; Angelberger, P.

    2002-01-01

    Aim: Receptors (R) for somatostatin (SST) are expressed on various tumor cells as well as activated leukocytes and other lymphoproliferative and immune cells. Our previous data have shown that various SST analogs including 111 In-OctreoScan, 111 In-DOTA-Lanreotide (DLAN), 111 In-DOTA-Tyr3-Octreotide (DTOCT) and 99m Tc-P829 bind with high affinity onto many different types of tumor cells as well as to leukocytes via hSSTR target receptors. We have evaluated the orbital uptake of these tracers in patients with active and inactive thyroid-associated orbitopathy. Material and Methods: Clinical grade of the orbital disease was documented in all patients (n=90) by the NOSPECS classification, the clinical activity score (CAS) as well as the supra nasal index (SNI) measured by standardized echography. 99m Tc-P829 scintigraphy (740 MBq) or scintigraphy with one of the 111 In-labeled SST analogs (150 MBq) was performed in patients with thyroid-associated orbitopathy (duration of the disease: 1 - 360 months). In patients undergoing 99m Tc-P829 scintigraphy, SPECT (360 deg.) and planar studies were completed within 3 h post injection, whereas most patients undergoing scintigraphy with 111 In-labeled SST analogs also had a 24 h image acquisition. Orbital (O) regions of interest (ROIs) were opposed to temporo-parietal (TP) and occipital (OCC) ROIs and the O/TP and O/OCC ratios were calculated. Uptake ratios in Graves disease were compared to orbital data calculated from cancer patients without eye disease. Results: Compared to clinical data, a significant correlation was found only for CAS (p 99m Tc-P829 images (three independent observers) despite of somewhat lower uptake both for O/TP as well as O/OCC uptake ratios. 111 In-DLAN and 111 In-DTOCT biokinetics were comparable in Graves disease patients showing a rapid blood clearance and visualization of the orbit within minutes of injection. In patients without active disease (O/(TP+OCC) / 2 ratio: 1.20 +/- 0.09) as well as in control patients (O / (TP+OCC) /2 ratio: 1.19 +/- 0.07) the orbit itself appeared as cold area. Visual orbital accumulation was found in all patients with active Graves ophthalmopathy ( 99m Tc-P829 uptake: O / (TP+OCC)/2 ratio: 1.5 +/- 0.09; 111 In-DLAN uptake: O / (TP+OCC)/2 ratio: 1.78 +/- 0.09, 111In-DTOCT ratio: 1.83 +/- 0.08 (p 99m Tc-P829, 111 In-DLAN and 111 In-DTOCT, all three yield high orbital binding for active orbitopathy associated with thyroid Graves disease. In-house availability of 99m Tc-P829, cost-effectiveness, lower radiation dose, shorter acquisition protocol and better image quality favor SSTR scintigraphy with 99m Tc-P829 over 111 In-labeled compounds

  20. [Study of anti-idiotype antibodies to human monoclonal antibody].

    Science.gov (United States)

    Harada, R; Takahashi, N; Owaki, I; Kannagi, R; Endo, N; Morita, N; Inoue, M

    1992-02-01

    A human monoclonal antibody, ll-50 (IgM, lambda), was generated, which reacted specifically with a major of glycolipid present in LS174T colon cancer cells. The glycolipid antigen which reacted with the ll-50 antibody was expected to four sugar residues from its TLC mobility, and it was ascertained that the glycolipid antigen which reacted with ll-50 antibody might be Lc4 antigen [Gal beta 1----3 GLcNAc beta 1----3 Gal beta 1----4 Glc beta 1----1 Cer] judging from TLC immunostaining and ELISA when the reactivity of ll-50 antibody was tested using various pure glycolipids in 3-5 sugar residues as an antigen. Sera in patients with malignant disorders and healthy individuals were analyzed by Sandwich assay of immobilized and biotinylated ll-50 antibody. The serum of the Lc4 antigen recognized by ll-50 antibody was significantly higher in patients with malignant disorders than that in healthy individuals (p less than 0.05). Three mouse monoclonal anti-idiotype antibodies, G3, B3 and C5 (all IgG1), were generated by the immunization of BALB/c mice with ll-50 antibody. These anti-idiotype antibodies specifically bound to to human monoclonal antibody, ll-50 and had a significant inhibitory activity towards the binding of ll-50 antibody to the Lc4 antigen. This indicated that these anti-idiotype antibodies, G3, B3, and C5, were paratope-related anti-idiotype antibodies. G3, B3, and C5 were expected to define the nearest idiotope because they could mutually inhibit ll-50 antibody. Sera in patients with malignant disorders and healthy individuals were analyzed by Sandwich assay of immobilized and biotinylated anti-idiotype antibodies, G3, B3, and C5. As to the ll-50 like antibodies defined by C5 (Id-C5+), the mean serum level in patients with malignant disorders was significantly higher than that in healthy individuals (p less than 0.05). As to the ll-50 like antibodies defined by B3 (Id-B3+), the mean serum level in patients with malignant disorders was significantly higher

  1. Imaging of melanoma with 131I-labeled monoclonal antibodies

    International Nuclear Information System (INIS)

    Larson, S.M.; Brown, J.P.; Wright, P.W.; Carrasquillo, J.A.; Hellstroem, I.; Hellstroem, K.E.

    1983-01-01

    Mouse monoclonal antibodies and Fab fragments specific for p97, a melanoma-associated antigen, were used to image metastatic human melanoma. Preclinical studies in athymic mice showed antigen-specific uptake in melanoma xenografts, and toxicity tests in rabbits gave no evidence for tissue damage after injection of up to 100 times the amount of antibody used in humans. Six patients received 1 mg labeled antibody, and one patient received 1 mg of labeled Fab. No. toxic side effects were observed. All of the six patients had positive scans, visualizing 22 of 25 (88%) of lesions larger than 1.5 cm. In tumors from two patients, greater uptake of p97-specific, versus control IgG and Fab, respectively, was documented by biopsy. Antibodies to mouse immunoglobulin appeared in three patients receiving 1 mg or more of radiolabeled mouse antibody

  2. A monoclonal antibody to pestviruses in bovine and ovine sera

    International Nuclear Information System (INIS)

    Mweene, A.S.

    1991-01-01

    An enzyme-linked immunoabsorbent assay (ELISA) has been developed to defeat antibodies to pestviruses in bovine and ovine sera. Single sera from 211 cattle and 22 sheep from 7 different farms were tested using ELISA and Serum Neutralisation Test (SNT). 17 Monoclonal antibodies (Mabs) directed against P80, gp48 and gp53 were tested for ability to coat ELISA plates and capture the bovine viral diarrhea antigen. 5 mabs(WB 103, WB, 105, WB 112 against P80 kDa protein, WB 210 and WB 214 directed against gp48 and gp 53 kDa protein. Specific antibody to BVDV was detected by rabbit anti-bovine and anti-ovine IgG antisera. The quantitative correlation between two tests was good

  3. Lymphocyte targeting with /sup 111/In-labelled monoclonal antibodies

    Energy Technology Data Exchange (ETDEWEB)

    Loutfi, I.; Batchelor, J.R.; Lavender, J.P.; Epenetos, A.A.

    1988-01-01

    In vitro tests were conducted using human T and B cell lines, as well as whole blood, to establish the usefulness of 2 murine monoclonal antibodies (MAbs), an anti-CD5 (Pan T) and a Pan B, for potential radioimmunolocalization and therapy. Both MAbs showed specificity for the cell line in question as tested by indirect immunofluorescence and radioimmunoassay. Assays carried out on whole blood showed 40-70% of the added activity of /sup 111/In-labelled Pan B antibody binding to B cells and 20-24% of /sup 111/In-Pan T antibody binding to T cells. The amount of internalised /sup 111/In-labelled Pan B was 6% of total amount at 24 hr indicating a slow internalization process. These results should allow for in vivo targeting of normal and neoplastic B and T cells.

  4. Epitope Mapping of Monoclonal Antibody PMab-48 Against Dog Podoplanin.

    Science.gov (United States)

    Yamada, Shinji; Kaneko, Mika K; Itai, Shunsuke; Chang, Yao-Wen; Nakamura, Takuro; Yanaka, Miyuki; Ogasawara, Satoshi; Murata, Takeshi; Uchida, Hiroaki; Tahara, Hideaki; Harada, Hiroyuki; Kato, Yukinari

    2018-04-02

    Podoplanin (PDPN), a type I transmembrane sialoglycoprotein, is expressed on normal renal podocytes, pulmonary type I alveolar cells, and lymphatic endothelial cells. Increased expression of PDPN in cancers is associated with poor prognosis and hematogenous metastasis through interactions with C-type lectin-like receptor 2 (CLEC-2) on platelets. We previously reported a novel PMab-48 antibody, which is an anti-dog PDPN (dPDPN) monoclonal antibody (mAb) recognizing PDPN expressed in lymphatic endothelial cells. However, the binding epitope of PMab-48 is yet to be clarified. In this study, an enzyme-linked immunosorbent assay and flow cytometry were used to investigate epitopes of PMab-48. The results revealed that the critical epitope of PMab-48 comprises Asp29, Asp30, Ile31, Ile32, and Pro33 of dPDPN.

  5. Characterization of monoclonal antibodies directed against human thyroid stimulating hormone

    International Nuclear Information System (INIS)

    Soos, M.; Siddle, K.

    1982-01-01

    Monoclonal antibodies directed against human thyroid stimulating hormone (TSH) were obtained from hybrid myelomas, following fusion of mouse NSI myeloma cells with mouse spleen cells. Ten different antibodies were obtained from 4 separate fusions. Eight antibodies were of the IgG 1 subclass. Affinities of antibodies for TSH were in the range 2 x 10 8 -5 x 10 10 M -1 . Five of the antibodies were specific for TSH and did not react with LH, FSH or hCG. The remaining antibodies reacted with all these hormones and were assumed to recognise their common (α) subunit. The 5 specific antibodies fell into 3 subgroups recognising distinct antigenic determinants, whereas the 5 non-specific antibodies recognised a single determinant or closely related set of sites. It is concluded that these antibodies should be valuable reagents for use in sensitive and specific two-site immunoradiometric assays. (Auth.)

  6. Identification of Eimeria acervulina conoid antigen using chicken monoclonal antibody.

    Science.gov (United States)

    Matsubayashi, Makoto; Minoura, Chisa; Kimura, Shintaro; Tani, Hiroyuki; Furuya, Masaru; Lillehoj, Hyun S; Matsuda, Haruo; Takenaka, Shigeo; Hatta, Takeshi; Tsuji, Naotoshi; Sasai, Kazumi

    2016-11-01

    In the poultry industry, Eimeria spp. is one of the important pathogens which cause significant economic losses. We have previously generated a chicken monoclonal antibody (mAb), 6D-12-G10, with specificity for an antigen located in the apical cytoskeleton of Eimeria acervulina and with cross-reactive among Apicomplexan parasites, including other Eimeria spp., Toxoplasma, Neospora, and Cryptosporidium spp. Furthermore, the protein of Cryptosporidium parvum recognized by the 6D-12-G10 has been identified as elongation factor-1α (EF-1α). In the present study, to identify the target molecule of E. acervulina by the mAb, we performed two-dimensional Western blotting analysis. Finally, we found two positive molecules which are identified as EF-1α and a related protein. Our previous finding using C. parvum and the results in this study suggest that EF-1α could be associated with the invasion facilitated by the cytoskeleton at the apical region of zoites.

  7. Enzymatic production of 'monoclonal stoichiometric' single-stranded DNA oligonucleotides.

    Science.gov (United States)

    Ducani, Cosimo; Kaul, Corinna; Moche, Martin; Shih, William M; Högberg, Björn

    2013-07-01

    Single-stranded oligonucleotides are important as research tools, as diagnostic probes, in gene therapy and in DNA nanotechnology. Oligonucleotides are typically produced via solid-phase synthesis, using polymer chemistries that are limited relative to what biological systems produce. The number of errors in synthetic DNA increases with oligonucleotide length, and the resulting diversity of sequences can be a problem. Here we present the 'monoclonal stoichiometric' (MOSIC) method for enzyme-mediated production of DNA oligonucleotides. We amplified oligonucleotides from clonal templates derived from single bacterial colonies and then digested cutter hairpins in the products, which released pools of oligonucleotides with precisely controlled relative stoichiometric ratios. We prepared 14-378-nucleotide MOSIC oligonucleotides either by in vitro rolling-circle amplification or by amplification of phagemid DNA in Escherichia coli. Analyses of the formation of a DNA crystal and folding of DNA nanostructures confirmed the scalability, purity and stoichiometry of the produced oligonucleotides.

  8. [Monoclonal antibodies for the treatment of multiple sclerosis].

    Science.gov (United States)

    Sánchez-Seco, Victoria Galán; Casanova Peño, Ignacio; Arroyo González, Rafael

    2014-12-01

    Until the mid 1990s, with the appearance of interferon beta and glatiramer acetate, there was no treatment for multiple sclerosis (MS). However, due to their moderate therapeutic potential in some patients, a broad search was continued to find new and more effective treatment strategies, largely concentrated on monoclonal antibodies (MOAB). Natalizumab, the first MOAB for the treatment of MS, was approved at the end of 2004, representing a major advance in the field of neuroimmunology. Today, there is broad experience with natalizumab and other MOAB (alemtuzumab, daclizumab, rituximab, ocrelizumab, ofatumumab and anti-lingo-1) that are pending commercialization or are under phase II or III of development with promising results. The present review analyzes the efficacy and safety results of all these drugs. Copyright © 2014 Elsevier España, S.L.U. All rights reserved.

  9. Primary hepatocellular carcinoma localised by a radiolabelled monoclonal antibody

    Energy Technology Data Exchange (ETDEWEB)

    Markham, N; Ritson, A; James, O; Curtin, N; Bassendine, M; Sikora, K

    1986-01-01

    A rat monoclonal antibody, YPC2/38.8, was selected from a panel of antibodies derived by immunising rats with fresh human colorectal carcinoma. It was found to bind to a 30,000 dalton protein present on the cell surface of normal colon and liver. This protein was increased 10-fold on primary hepatocellular carcinoma (PHC) cells. After labelling with /sup 131/I, YPC2/38.8 was shown to localise human PHCs grown as xenografts in immunosuppressed mice. The authors conclude that YPC2/38.8 may have potential for diagnostic localisation and possibly thence for the selective targeting of drugs or toxins in patients with PHC arising in a liver unaffected by significant parenchymal disease. 16 refs.; 4 figs.; 1 table.

  10. Regulation of Monoclonal Antibody Immunotherapy by FcγRIIB.

    Science.gov (United States)

    Stopforth, Richard J; Cleary, Kirstie L S; Cragg, Mark S

    2016-05-01

    Monoclonal antibodies (mAb) are revolutionising the treatment of many different diseases. Given their differing mode of action compared to most conventional chemotherapeutics and small molecule inhibitors, they possess the potential to be independent of common modes of treatment resistance and can typically be combined readily with existing treatments without dose-limiting toxicity. However, treatments with mAb rarely result in cure and so a full understanding of how these reagents work and can be optimised is key for their subsequent improvement. Here we review how an understanding of the biology of the inhibitory Fc receptor, FcγRIIB (CD32B), is leading to the development of improved mAb treatments.

  11. Microbials for the production of monoclonal antibodies and antibody fragments.

    Science.gov (United States)

    Spadiut, Oliver; Capone, Simona; Krainer, Florian; Glieder, Anton; Herwig, Christoph

    2014-01-01

    Monoclonal antibodies (mAbs) and antibody fragments represent the most important biopharmaceutical products today. Because full length antibodies are glycosylated, mammalian cells, which allow human-like N-glycosylation, are currently used for their production. However, mammalian cells have several drawbacks when it comes to bioprocessing and scale-up, resulting in long processing times and elevated costs. By contrast, antibody fragments, that are not glycosylated but still exhibit antigen binding properties, can be produced in microbial organisms, which are easy to manipulate and cultivate. In this review, we summarize recent advances in the expression systems, strain engineering, and production processes for the three main microbials used in antibody and antibody fragment production, namely Saccharomyces cerevisiae, Pichia pastoris, and Escherichia coli. Copyright © 2013 Elsevier Ltd. All rights reserved.

  12. Epitope Mapping of Monoclonal Antibody PMab-38 Against Dog Podoplanin.

    Science.gov (United States)

    Chang, Yao-Wen; Yamada, Shinji; Kaneko, Mika K; Kato, Yukinari

    2017-12-01

    Podoplanin (PDPN), a type I transmembrane sialoglycoprotein, is extensively expressed by normal lymphatic endothelial cells, renal podocytes, and pulmonary type I alveolar cells. Nevertheless, increased expression of PDPN in malignant tumors not only associates with poor prognosis but also facilitates hematogenous metastasis through interaction with C-type lectin-like receptor-2 presented on platelets, followed by PDPN-mediated platelet activation. We previously reported a novel PMab-38 antibody, an anti-dog PDPN (dPDPN) monoclonal antibody, which specifically recognizes PDPN in squamous cell carcinomas melanomas and cancer-associated fibroblasts in canine cancer tissues. However, the specific binding with the epitope of PMab-38 remains undefined. In this study, flow cytometry was utilized to investigate the epitope of PMab-38, which was determined using a series of deletion or point mutants of dPDPN. The results revealed that the critical epitope of PMab-38 is Tyr67 and Glu68 of dPDPN.

  13. Mass spectrometry for the biophysical characterization of therapeutic monoclonal antibodies.

    Science.gov (United States)

    Zhang, Hao; Cui, Weidong; Gross, Michael L

    2014-01-21

    Monoclonal antibodies (mAbs) are powerful therapeutics, and their characterization has drawn considerable attention and urgency. Unlike small-molecule drugs (150-600 Da) that have rigid structures, mAbs (∼150 kDa) are engineered proteins that undergo complicated folding and can exist in a number of low-energy structures, posing a challenge for traditional methods in structural biology. Mass spectrometry (MS)-based biophysical characterization approaches can provide structural information, bringing high sensitivity, fast turnaround, and small sample consumption. This review outlines various MS-based strategies for protein biophysical characterization and then reviews how these strategies provide structural information of mAbs at the protein level (intact or top-down approaches), peptide, and residue level (bottom-up approaches), affording information on higher order structure, aggregation, and the nature of antibody complexes. Copyright © 2013 Federation of European Biochemical Societies. Published by Elsevier B.V. All rights reserved.

  14. Monoclonal Antibodies Radiolabeling with Rhenium-188 for Radioimmunotherapy

    Science.gov (United States)

    Martini, Petra; Pasquali, Micol

    2017-01-01

    Rhenium-188, obtained from an alumina-based tungsten-188/rhenium-188 generator, is actually considered a useful candidate for labeling biomolecules such as antibodies, antibody fragments, peptides, and DNAs for radiotherapy. There is a widespread interest in the availability of labeling procedures that allow obtaining 188Re-labeled radiopharmaceuticals for various therapeutic applications, in particular for the rhenium attachment to tumor-specific monoclonal antibodies (Mo)Abs for immunotherapy. Different approaches have been developed in order to obtain 188Re-radioimmunoconjugates in high radiochemical purity starting from the generator eluted [188Re]ReO4−. The aim of this paper is to provide a short overview on 188Re-labeled (Mo)Abs, focusing in particular on the radiolabeling methods, quality control of radioimmunoconjugates, and their in vitro stability for radioimmunotherapy (RIT), with particular reference to the most important contributions published in literature in this topic. PMID:28951872

  15. Noninvasive diagnosis of axillary node metastases with monoclonal antibody lymphoscintigraphy

    International Nuclear Information System (INIS)

    Fig, L.M.; Von Moll, L.; Brown, R.; Harness, J.; Appleman, H.; Stevens, R.; Johnson, J.W.; Mudgett, E.; Colcher, D.; Schlom, J.; Lichter, A.; Wicha, M.; Wahl, R.L.

    1989-01-01

    This study was undertaken to determine whether 131-I labeled B72.3 monoclonal antibody, when injected subcutaneously in patients with known breast cancer, successfully detects lymph node metastases. Eleven women with biopsy-proven B72.3 antibody-reactive breast cancer (determined by immunoperoxidase staining) received subcutaneous injections of 500 μ Ci 131-I B72.3 in ipsilateral finger web spaces (or, in three cases, intralesional injections into the site of the breast tumor). The antibody is a IgGlk reactive with a high molecular weight antigen found on most breast carcinomas. Images of the axilla were obtained immediately after injection and serially to 72 hours. Nodal uptake was scored on a 0-3+ scale in a blinded fashion and correlated with pathologic findings from lymph node dissection

  16. Production of monoclonal antibody against Salmonella typhimurium by hybridoma technique

    International Nuclear Information System (INIS)

    Hasibuan, Adria P M; Sadi, Suharni

    1998-01-01

    In this research S.typhimurium killed by irradiation was used as antigen was prepared by exposing the bacteria to gamma rays from 60 Cobalt source with the dose of 2.5 kGy, Specific lymphocyte cell were obtained by immunizing 3 months old Balb-C mice with the antigen. the immunizations were done by subcutan route with the interval of 2 weeks. The hybridoma cells were made by fussing the specific lymphocyte cells with the myeloma cells. It was found that the animals (immunization + irradiation with a low dose of I Gy ) yielded monoclonal antibody with higher value (5.15 mg/ml) than the control animals (3.25 mg/ml). (author)

  17. Iodination of monoclonal antibodies, proteins and peptide using iodogen

    Energy Technology Data Exchange (ETDEWEB)

    Zhanpo, Niu [Chinese Academy of Medical Sciences, Beijing, BJ (China). PUMC Hospital; and others

    1988-05-01

    The use of the iodinating reagent 1,3,4,6-tetrachloro-3{alpha}, 6{alpha}-diphenylglycholuril (Iodogen) to label monoclonal antibodies (McAbs). Proteins and peptides was invesrigated with McAbs identified as mouse IgG and IgM, arginine-vasopressin (AVP), glucagon (Glu), human insulin(hI) and albumin(Alb). The labeled products were purified by gel chromatography and their immunoreactivity were detected by RIA or IRMA> Comparison of the Iodogen method with the lactoperoxides and chloramine-T methods showed that the Iodogen method had a number of advantages: (1) technically simpler ; (2) a high labeling efficiency could be obtained; (3) the immunoreactivity of the products was minimally affected; (4) the products were stable for up to 4 months.

  18. PCSK9 Inhibition With Monoclonal Antibodies: Modern Management of Hypercholesterolemia

    Science.gov (United States)

    Santos, Raul D.

    2016-01-01

    Abstract Current guidelines for hypercholesterolemia treatment emphasize lifestyle modification and lipid‐modifying therapy to reduce the risk for cardiovascular disease. Statins are the primary class of agents used for the treatment of hypercholesterolemia. Although statins are effective for many patients, they fail to achieve optimal reduction in lipids for some patients, including those who have or are at high risk for cardiovascular disease. The PCSK9 gene was identified in the past decade as a potential therapeutic target for the management of patients with hypercholesterolemia. Pharmacologic interventions to decrease PCSK9 levels are in development, with the most promising approach using monoclonal antibodies that bind to PCSK9 in the plasma. Two monoclonal antibodies, alirocumab and evolocumab, have recently been approved for the treatment of hypercholesterolemia, and a third one, bococizumab, is in phase 3 clinical development. All 3 agents achieve significant reductions in levels of low‐density lipoprotein cholesterol, as well as reductions in non‐high‐density lipoprotein cholesterol, apolipoprotein B, and lipoprotein(a). Long‐term outcome trials are under way to determine the sustained efficacy, safety, and tolerability of PCSK9 inhibitors and whether this novel class of agents decreases the risk for major cardiovascular events in patients on lipid‐modifying therapy. Available data suggest that PCSK9 inhibitors provide a robust reduction in atherogenic cholesterol levels with a good safety profile, especially for patients who fail to obtain an optimal clinical response to statin therapy, those who are statin intolerant or have contraindications to statin therapy, and those with familial hypercholesterolemia. PMID:27195910

  19. Preparation of monoclonal antibodies against radiation-induced protein

    International Nuclear Information System (INIS)

    Nozawa, R.; Tanaka, A.; Watanabe, H.; Kitayama, S.

    1992-01-01

    We obtained the 6 monoclonal antibodies against gamma-induced proteins of Deinococcus radiodurans, and these antibodies were designated as Mab-3F, 4B, 4D, 4F, 4G and 12G. Using these antibodies, we investigated the relations between gamma-induced proteins and other stress protein in strain R1, and the induction of proteins were compared among strain R1, resistant mutant (rec1) and radiosensitive mutant (rec30). We found new 6 proteins recognized by these monoclonal antibodies which were induced after gamma-irradiation especially in strain R1 and rec 1, but not induced in strain rec30. We suppose that these proteins participate in repair of DNA damages including double strand breaks caused by gamma-irradiation. One of them was around 46kDa protein band recognized by Mab-12G, and this protein was so induced in a large quantity after irradiation that the protein could detect by gold staining. In addition to this observation, we found some proteins which were induced in R1 and rec 1 by gamma-irradiation and other stress, but not in strain rec30, such as 31kDa protein band recognized by Mab-3F, 4B and 4G, and other 11 proteins which were especially induced in irradiated strain R1. The latter proteins might be reinforcement factor to radioresistance such as GroE and DnaK, or participant in repair of damage by gamma-irradiation in strain R1. (author)

  20. Selectivity verification of cardiac troponin monoclonal antibodies for cardiac troponin detection by using conventional ELISA

    Science.gov (United States)

    Fathil, M. F. M.; Arshad, M. K. Md; Gopinath, Subash C. B.; Adzhri, R.; Ruslinda, A. R.; Hashim, U.

    2017-03-01

    This paper presents preparation and characterization of conventional enzyme-linked immunosorbent assay (ELISA) for cardiac troponin detection to determine the selectivity of the cardiac troponin monoclonal antibodies. Monoclonal antibodies, used to capture and bind the targets in this experiment, are cTnI monoclonal antibody (MAb-cTnI) and cTnT monoclonal antibody (MAb-cTnT), while both cardiac troponin I (cTnI) and T (cTnT) are used as targets. ELISA is performed inside two microtiter plates for MAb-cTnI and MAb-cTnT. For each plate, monoclonal antibodies are tested by various concentrations of cTnI and cTnT ranging from 0-6400 µg/l. The binding selectivity and level of detection between monoclonal antibodies and antigen are determined through visual observation based on the color change inside each well on the plate. ELISA reader is further used to quantitatively measured the optical density of the color changes, thus produced more accurate reading. The results from this experiment are utilized to justify the use of these monoclonal antibodies as bio-receptors for cardiac troponin detection by using field-effect transistor (FET)-based biosensors coupled with substrate-gate in the future.

  1. Two-site sandwich radioimmunoassay of human gamma interferon with monoclonal antibodies

    Energy Technology Data Exchange (ETDEWEB)

    Tanaka, E; Imai, M; Usuda, S; Tachibana, K; Okamoto, H; Ohike, Y; Nakamura, T; Miyakawa, Y; Mayumi, M [Jichi Medical School, Minamikawachi, Tochigi (Japan)

    1985-03-18

    Two monoclonal antibodies were raised against human gamma interferon (IFN-..gamma..) derived from E. coli harboring the recombinant cDNA for IFN-..gamma.., and one against a synthetic peptide representing its C-terminus amino acid sequence of 20 residues. The monoclonal antibody against the synthetic peptide reacted either with IFN-..gamma.. or the synthetic peptide. One monoclonal anti-IFN-..gamma.. did not react with the synthetic peptide, while the other showed a weak binding with the peptide. A 2-site '1-step' radioimmunoassay was developed. The assay was rapid with a sensitivity capable of detecting a few ng/ml of IFN-..gamma...

  2. Mammalian tissue distribution of a large heparan sulfate proteoglycan detected by monoclonal antibodies

    DEFF Research Database (Denmark)

    Couchman, J R; Ljubimov, A V

    1989-01-01

    muscle, endothelia, peripheral nerve fibers and epithelia so far examined. In addition, two of the monoclonal antibodies show cross-species reactivity, staining bovine and human basement membranes, and immunoprecipitating proteoglycans from human endothelial cell cultures. These antibodies do not......A panel of nine monoclonal antibodies has been characterized, all of which have reactivity with the core protein of a large heparan sulfate proteoglycan derived from the murine EHS tumor matrix. These rat monoclonal antibodies stained mouse basement membranes intensely, including those of all...

  3. Efficient generation of monoclonal antibodies against peptide in the context of MHCII using magnetic enrichment.

    Science.gov (United States)

    Spanier, Justin A; Frederick, Daniel R; Taylor, Justin J; Heffernan, James R; Kotov, Dmitri I; Martinov, Tijana; Osum, Kevin C; Ruggiero, Jenna L; Rust, Blake J; Landry, Samuel J; Jenkins, Marc K; McLachlan, James B; Fife, Brian T

    2016-06-13

    Monoclonal antibodies specific for foreign antigens, auto-antigens, allogeneic antigens and tumour neo-antigens in the context of major histocompatibility complex II (MHCII) are highly desirable as novel immunotherapeutics. However, there is no standard protocol for the efficient generation of monoclonal antibodies that recognize peptide in the context of MHCII, and only a limited number of such reagents exist. In this report, we describe an approach for the generation and screening of monoclonal antibodies specific for peptide bound to MHCII. This approach exploits the use of recombinant peptide:MHC monomers as immunogens, and subsequently relies on multimers to pre-screen and magnetically enrich the responding antigen-specific B cells before fusion and validation, thus saving significant time and reagents. Using this method, we have generated two antibodies enabling us to interrogate antigen presentation and T-cell activation. This methodology sets the standard to generate monoclonal antibodies against the peptide-MHCII complexes.

  4. Metal chelate conjugated monoclonal antibodies, wherein the metal is an α emitter

    International Nuclear Information System (INIS)

    Gansow, O.A.; Strand, M.

    1984-01-01

    Methods of manufacturing and purifying metal chelate conjugated monoclonal antibodies are described, wherein the chelated metal emits alpha radiation. The conjugates are suited for therapeutic uses being substantially free of nonchelated radiometal. (author)

  5. Utility of testing for monoclonal bands in serum of patients with suspected osteoporosis

    DEFF Research Database (Denmark)

    Abrahamsen, B.; Andersen, Ivan; Christensen, Susanne S.

    2005-01-01

    OBJECTIVE: To determine whether measuring monoclonal bands (M component) in serum should be part of the investigation of patients referred to osteoporosis clinics. DESIGN: Retrospective, cross sectional, observational study. SETTING: Referral centre for osteoporosis in a university hospital...

  6. Use of monoclonal-antibodies for the detection of fecal bacteria in water

    CSIR Research Space (South Africa)

    Kfir, R

    1993-01-01

    Full Text Available Monoclonal antibodies (MAbs) against heat-killed Escherichia coli and Klebsiella oxytoca originating from wastewater effluent were raised in BALB/C mice. The fusion was highly successful and three hybridomas cloned were selected to study...

  7. Enzymatic extraction of cobalamin from monoclonal antibody captured haptocorrin and transcobalamin

    DEFF Research Database (Denmark)

    Hardlei, Tore Forsingdal; Mørkbak, Anne Louise; Nexo, Ebba

    2007-01-01

    OBJECTIVES: Current extraction methods for cobalamins from serum influence the molecular characteristics of the vitamin. Therefore, an extraction procedure that leaves the cobalamins unchanged is needed. DESIGN AND METHODS: Monoclonal antibodies towards transcobalamin (TC) and haptocorrin (HC) (in...

  8. Single-domain monoclonal antibodies for the treatment of hepatocellular carcinoma | NCI Technology Transfer Center | TTC

    Science.gov (United States)

    The National Cancer Institute seeks parties to license human monoclonal antibodies and immunoconjugates and co-develop, evaluate, and/or commercialize large-scale antibody production and hepatocellular carcinoma (HCC) xenograft mouse models.

  9. NCI Requests Cancer Targets for Monoclonal Antibody Production and Characterization | Office of Cancer Clinical Proteomics Research

    Science.gov (United States)

    In an effort to provide well-characterized monoclonal antibodies to the scientific community, NCI's Antibody Characterization Program requests cancer-related protein targets for affinity production and distribution. Submissions will be accepted through July 11, 2014.

  10. NCI Requests Targets for Monoclonal Antibody Production and Characterization | Office of Cancer Clinical Proteomics Research

    Science.gov (United States)

    In an effort to provide well-characterized monoclonal antibodies to the scientific community, NCI's Antibody Characterization Program requests cancer-related protein targets for affinity production and distribution. Submissions will be accepted through July 9, 2012.

  11. Human monoclonal antibody as prophylaxis for SARS coronavirus infection in ferrets

    NARCIS (Netherlands)

    ter Meulen, Jan; Bakker, Alexander B. H.; van den Brink, Edward N.; Weverling, Gerrit J.; Martina, Byron E. E.; Haagmans, Bart L.; Kuiken, Thijs; de Kruif, John; Preiser, Wolfgang; Spaan, Willy; Gelderblom, Hans R.; Goudsmit, Jaap; Osterhaus, Albert D. M. E.

    2004-01-01

    SARS coronavirus continues to cause sporadic cases of severe acute respiratory syndrome (SARS) in China. No active or passive immunoprophylaxis for disease induced by SARS coronavirus is available. We investigated prophylaxis of SARS coronavirus infection with a neutralising human monoclonal

  12. The effect of immunomodulators on the immunogenicity of TNF-blocking therapeutic monoclonal antibodies: a review

    NARCIS (Netherlands)

    Krieckaert, C.L.; Bartelds, G.M.; Lems, W.F.; Wolbink, G.J.

    2010-01-01

    Therapeutic monoclonal antibodies have revolutionized the treatment of various inflammatory diseases. Immunogenicity against these antibodies has been shown to be clinically important: it is associated with shorter response duration because of diminishing concentrations in the blood and with

  13. Use of AN Eosinophil Specific Monoclonal Antibody in Assessing Eosinophil Function.

    Science.gov (United States)

    Minkoff, Marjorie Sue

    A monoclonal antibody to an eosinophil specific determinant is very important in assessing eosinophil function during helminthic infection. Eosinophils induced by Schistosoma mansoni infection in BALB/c mice were used to induce C57B1/6 immunocytes for production of hybridomas secreting eosinophil monoclonal antibodies. These antibodies were shown to react with an eosinophil surface epitope but not with neutrophils or macrophages as determined by ELISA, immunodiffusion, immunofluorescence, and immunoblot assay. Affinity chromatography with eosinophil chemotactic factor-sepharose consistently selected out a { rm M_ R} 67,000 protein from solubilized eosinophil membrane antigens but not from neutrophil and macrophage antigens. In vitro studies showed that the eosinophil-specific monoclonal antibodies abrogated antibody-dependent eosinophil -mediated killing of S. mansoni schistosomula using mouse, rat or human eosinophils. Neutrophil and macrophage killing activities were unaffected. The monoclonal antibodies effected complement-dependent lysis of mouse and rat eosinophils but not of human eosinophils. ECF-treated eosinophils showed enhanced killing of schistosomula which was blocked by the monoclonal antibody. Murine and human eosinophils preincubated with monoclonal antibody exhibited decreased chemotaxis to ECF at optimal chemotactic concentrations. The monoclonal antibody also blocked eosinophil binding to ECF- sepharose beads. In vivo induction of peripheral blood eosinophilia by injection of S. mansoni eggs was suppressed by injections of monoclonal antibodies 2CD13 and 2QD45 in mouse and rat experimental models. Eosinophilia induced by keyhole limpet hemocyanin- cyclophosphamide treatment was also suppressed by monoclonal antibody in both murine and rat systems. Pulmonary granulomas in mice given egg injection and monoclonal antibody were smaller and contained fewer eosinophils than those granulomas from mice given eggs only. In immuno-biochemical studies, the

  14. Monoclonal antibodies against pregnancy-specific β1-glycoprotein (SP1) in immunohistochemistry and radioimmunoassay

    International Nuclear Information System (INIS)

    Wahlstroem, T.; Heikinheimo, M.

    1983-01-01

    Monoclonal mouse antibodies against pregnancy-specific beta-1-glycoprotein (SP 1 ) have been studied for their suitability in immunoperoxidase staining and radioimmunoassay methodologies. These antibodies were useful in staining normal placentas, hydatidiform moles, invasive moles and choriocarcinomas. They showed good specificity, with minimal background staining, and will thus be superior to conventional polyclonal antisera in immunohistochemistry. However, the presently tested monoclonal anti-SP 1 antibodies were found not to be suitable for radioimmunoassay. (Auth.)

  15. [Diagnostic and therapeutic use of human anti-D (Rho) monoclonal antibodies. Evaluation and perspectives].

    Science.gov (United States)

    Rouger, P; Goossens, D; Champomier, F; Tsikas, G; Liberge, G; Leblanc, J; Richard, C; Bailleul, C; Salmon, C

    1985-12-01

    Human monoclonal antibodies will be essential in medicine. They are valuable tools for biological diagnosis and therapeutics. Our model, human monoclonal antibodies directed against the Rhesus D antigen can be used for the determination of the Rhesus D phenotype and for the suppression of Rh(D) immunisation in women. These new products require new procedures of preparation, new regulations for the quality controls, which will be discussed in this paper.

  16. The development of glioblastoma multiforme reactive monoclonal antibodies and their use in drug targeting

    International Nuclear Information System (INIS)

    Klaich, G.M.

    1989-01-01

    The objectives of this project were to develop monoclonal antibodies reactive with the tumor glioblastoma multiforme and to use them to study and develop new treatment modalities for this disease. A tumor antigen enriched immunogen, prepared by immunoaffinity chromatography, was compared to a whole tumor homogenate immunogen with the difference in the yield of tumor reactive, normal brain unreactive monoclonal antibodies proving to be significant. Monoclonal antibody A7, reactive with tumor tissue but unreactive with normal tissue, was isotyped to be an IgG2a immunoglobulin and could be purified to electrophoretic homogeneity by using serum-free culture conditions and protein A sepharose chromatography. Monoclonal antibody A7 is noncytotoxic as measured by the 3 H-nicotinamide release assay and binds to a 138 kd membrane antigen which is not internalized. Localization studies using 14 C-labeled monoclonal antibody A7 and the U-87 MG nude mouse xenograft model resulted in a tumor:serum ratio of 1.25:1.0 as compared to 0.29:1.0 for the negative control. A monoclonal antibody A7-doxorubicin immunoconjugate proved to be more cytotoxic than free doxorubicin in vitro while lethality studies using Swiss mice demonstrated the lack of toxicity of the immunoconjugate as compared to free doxorubicin. In vivo chemotherapy studies using the U-87 MG nude mouse xenograft failed to demonstrate any immunoconjugate anti-tumor activity which may be attributable to the route of administration

  17. Monoclonal antibodies as reversible equilibrium carriers of radiopharmaceuticals

    International Nuclear Information System (INIS)

    Goodwin, D.A.; McTigue, M.; Meares, C.F.; McCall, M.J.; David, G.F.; Frincke, J.M.; Stone, M.R.; Bartholomew, R.M.; Leung, J.P.

    1986-01-01

    The authors have prepared monoclonal antibodies (MoAbs) with the specific ability to bind metal chelates such as 111 In benzyl EDTA. One, 10, 50 and 100 μg MoAb CHA255 Ksub(b) 4 x 10E9 was complexed with 111 In BLEDTA II, BLEDTA IV, and benzyl EDTA and injected i.v. in Balb/c mice with KHJJ tumor. The biological half-life by whole body counting was profoundly altered for all three compounds; from minutes to hours with 10 μg; to days with 100 μg. Tumor uptake increased 50 fold at 24 h with increasing MoAb but satisfactory tumor concentrations (3% per g) and tumor/blood ratios (1.8:1) were obtained with an amount equivalent to 7 mg for a human. Blood level and whole body activity were decreased 30-50% within 3 h or i.v. injection of a 'flushing' dose of unlabeled indium benzyl EDTA, increasing tumor/blood ratios to 50:1. (author)

  18. Gamma radiations an effective way of monoclonal antibodies sterilization

    International Nuclear Information System (INIS)

    Lenay Barrera Barroso, Lenay; Otero Abreu, Isabel; Rodriguez Napoles, Dania; Bulte Ocanna, Dubhe; Caballero, Idania

    2006-01-01

    The sterilization for radiations of pharmaceutical products is an effective, sure and reliable procedure; that it have been proving technically and grateful for different pharmacopoeia. The Monoclonal Antibodies (Acm) produced in the Center of Molecular Immunology (CIM) are products parenteral for the one which results indispensable that they complete the requirements of established sterility. The radio sterilization result the method more recommend for the sterilization of the Acm deep drying, due to the contained first floor of humidity remnant that minimizes the formation of sub-product that they affect their properties. With the objective of proposing a good dose of irradiation for the sterilization, we were carried out a study of the radius sensibility so much of the product like of the polluting of greater frequency of isolation of the clean area of the CIM. The characterization of the radius sensibility of the different micro- organisms was determined by D 10 characteristic of each isolated strains. From the developed studies the Gram-positive rods endospore-forming were the most resistant strains at the deep drying, the radiations and they were of the greater frequency of apparition in the carried out isolations. We could conclude that utilizing a dose of 10 kGy it is possible to eliminate of the pollution more radio resistant, assuring the sterility required in the product, and without inducing effects under desire radiolytic in the same

  19. Isolation of monoclonal antibodies with predetermined conformational epitope specificity.

    Directory of Open Access Journals (Sweden)

    Anton M Sholukh

    Full Text Available Existing technologies allow isolating antigen-specific monoclonal antibodies (mAbs from B cells. We devised a direct approach to isolate mAbs with predetermined conformational epitope specificity, using epitope mimetics (mimotopes that reflect the three-dimensional structure of given antigen subdomains. We performed differential biopanning using bacteriophages encoding random peptide libraries and polyclonal antibodies (Abs that had been affinity-purified with either native or denatured antigen. This strategy yielded conformational mimotopes. We then generated mimotope-fluorescent protein fusions, which were used as baits to isolate single memory B cells from rhesus monkeys (RMs. To amplify RM immunoglobulin variable regions, we developed RM-specific PCR primers and generated chimeric simian-human mAbs with predicted epitope specificity. We established proof-of-concept of our strategy by isolating mAbs targeting the conformational V3 loop crown of HIV Env; the new mAbs cross-neutralized viruses of different clades. The novel technology allows isolating mAbs from RMs or other hosts given experimental immunogens or infectious agents.

  20. Clinical application of antibody monoclonal humanized anti-EGFrnimotuzumab labeled

    International Nuclear Information System (INIS)

    Perera Pintado, Alejandro; Peña Quián, Yamilé; Batista Cuéllar, Juan F.; Prats Capote, Anaís; Torres Aroche, Leonel A.; Casacó Santana, Caridad; Sánchez Mendosa, Elvia L.; Sánchez González, Yolaine; Romero Collado, Susana; Quesada Pozo, Rodobaldo; Valladares Oviedo, Lourdes; Masquida García, Elsa M.; Leyva Montaña, René; Casacó, Angel; Ramos Suzarte, Mayra; Crombet, Tania

    2016-01-01

    Most malignant tumors are of epithelial origin. These are characterized by overexpression of the receptor of epidermal growth factor (EGFR), which the neoplastic cells escape the regulatory mechanisms are allowed, so its high concentration of membrane is generally associated with a poor prognosis . By binding an antibody specifically to this receptor, preventing binding of EGF latter and activation mechanism tyrosine kinase inhibiting cell mitosis and apoptosis causing tumor cell. For this reason, the EGFr has been considered as an attractive target for anti-tumor therapy. The humanized monoclonal antibody anti-EGFr nimotuzumab was developed by the Center of Molecular Immunology (Havana, Cuba). Numerous clinical trials have been developed in the Department of Clinical Research Center Isotopes (Cuba), in which it has been applied this antibody, both labeled with 99mTc for immuno gammagraphic detection of tumors, as labeled with 188 Re for radioimmunotherapy of gliomas high degree of malignancy. The aim of this paper is to show the experience of the Department of Clinical Research of CENTIS in various clinical trials with marking for both immuno gammagraphics detection of tumors, such as for radioimmunotherapy nimotuzumab. (author)

  1. Radioimmunodetection of colorectal cancer, using anti-CEA monoclonal antibodies

    International Nuclear Information System (INIS)

    Murayama, Hiroki; Watanabe, Tadashi; Tadokoro, Masanori; Takagi, Hiroshi; Sakuma, Sadayuki; Sakamoto, Junichi.

    1989-01-01

    Aiming at radioimmunodetection of colorectal cancer, anti-CEA monoclonal antibodies (CEA102) were produced by immunization with purified CEA. CEA102 showed high specificity with clorectal cancer by mixed hemadsorption assay and immunoperoxidase technique. The antigen detected by CEA102 was confirmed to be carcinoembryonic antigen (CEA) and its molecular weight was estimated to be ca. 180,000 by biochemical analysis. The in vivo study using nude mice grafted a human colorectal cancer or a human malignant melanoma showed greater accumulation of 125 I-labeled CEA102 in CEA-positive colorectal cancer than in nude mouse tissues and CEA-negative malignant melanoma. Moreover we successfully obtained scans with good localization of the grafted colorectal cancer on FCR (Fuji Computed Radiography). Using 131 I-labeled CEA102 liver metastasis in the patient with colorectal cancer was successfully detected by external scanning with γ-camera. These results suggest that radiolabeled CEA102 is useful for the detection of colorectal cancer. (author)

  2. Radiolabelled monoclonal antibodies: magic bullets for colorectal carcinoma

    International Nuclear Information System (INIS)

    Slade, Linda

    1997-01-01

    Radiolabelled monoclonal antibodies (MoAbs) have been heralded as highly specific detection agents for many types of tumours. However, because of the many problems that have been associated with the use of these agents, their development and successes did not meet expectations. This paper discusses the use of radiolabelled MoAbs in the diagnosis and staging of colorectal cancer, the type of antibodies and radionuclides investigated over the past thirty years, and the advantages and disadvantages of each. An attempt is made to define the role of radioimmunoscintigraphy (RIS) in the investigation and management of patients with colorectal cancer. It appears that this technique can improve tumour detection, especially when used in conjunction with other imaging modalities. High sensitivities and specificities have been found using radio-labelled MoAbs for investigation of colorectal carcinoma. However, the author estimates there are a number of areas that require further research and improvement before naming radiolabelled MoAbs as 'magic bullets' for colorectal cancer. 8 refs., 3 tabs

  3. Microfluidic model experiments on the injectability of monoclonal antibody solutions

    Science.gov (United States)

    Duchene, Charles; Filipe, Vasco; Nakach, Mostafa; Huille, Sylvain; Lindner, Anke

    2017-11-01

    Autoinjection devices that allow patients to self-administer medicine are becoming used more frequently; however, this advance comes with an increased need for precision in the injection process. The rare occurrence of protein aggregates in solutions of monoclonal antibodies constitutes a threat to the reliability of such devices. Here we study the flow of protein solutions containing aggregates in microfluidic model systems, mimicking injection devices, to gain fundamental understanding of the catastrophic clogging of constrictions of given size. We form aggregates by mechanically shaking or heating antibody solutions and then inject these solutions into microfluidic channels with varying types of constrictions. Geometrical clogging occurs when aggregates reach the size of the constriction and can in some cases be undone by increasing the applied pressure. We perform systematic experiments varying the relative aggregate size and the flow rate or applied pressure. The mechanical deformation of aggregates during their passage through constrictions is investigated to gain a better understanding of the clogging and unclogging mechanisms.

  4. Defining process design space for monoclonal antibody cell culture.

    Science.gov (United States)

    Abu-Absi, Susan Fugett; Yang, LiYing; Thompson, Patrick; Jiang, Canping; Kandula, Sunitha; Schilling, Bernhard; Shukla, Abhinav A

    2010-08-15

    The concept of design space has been taking root as a foundation of in-process control strategies for biopharmaceutical manufacturing processes. During mapping of the process design space, the multidimensional combination of operational variables is studied to quantify the impact on process performance in terms of productivity and product quality. An efficient methodology to map the design space for a monoclonal antibody cell culture process is described. A failure modes and effects analysis (FMEA) was used as the basis for the process characterization exercise. This was followed by an integrated study of the inoculum stage of the process which includes progressive shake flask and seed bioreactor steps. The operating conditions for the seed bioreactor were studied in an integrated fashion with the production bioreactor using a two stage design of experiments (DOE) methodology to enable optimization of operating conditions. A two level Resolution IV design was followed by a central composite design (CCD). These experiments enabled identification of the edge of failure and classification of the operational parameters as non-key, key or critical. In addition, the models generated from the data provide further insight into balancing productivity of the cell culture process with product quality considerations. Finally, process and product-related impurity clearance was evaluated by studies linking the upstream process with downstream purification. Production bioreactor parameters that directly influence antibody charge variants and glycosylation in CHO systems were identified.

  5. Production of human anti-HLA monoclonal antibodies

    Energy Technology Data Exchange (ETDEWEB)

    Walker, M.C.; Mercier, F.; Roger, J.; Varin, M.

    1986-03-01

    Only 40% of the several hundred anti-HLA murine monoclonal antibodies (MAbs) that have been made detect HLA-A,B,C or DR specificities previously defined by human alloantisera, the range of recognized specificities is very narrow, and few of the MAbs have proven useful as tissue typing reagents. In hopes of obtaining HLA typing reagents, the authors are developing a protocol for the production of human anti-HLA MAbs from HLA-antigen (Ag) immunized peripheral blood B cells of volunteering renal patients, immunized to one or more HLA Ags through therapeutic blood transfusions. A simple enrichment of the donor B cells has not been sufficient for anti-HLA MAb production, the authors are currently delineating the conditions necessary for increasing the number of HLA-specific donor B cells by in vitro stimulation with cells expressing the HLA Ag to which the B cell donor is immunized. For the production of MAbs, the stimulated B cells are transformed with Epstein-Barr virus and subsequently fused with KR-4 lymphoblastoid cells. Hybridomas are selected by HAT and Ouabain. Supernatants are screened for anti-HLA activity against lymphocyte targets expressing the original immunizing HLA Ag by complement mediated /sup 51/Cr release assay. Antibody specificity is determined by the complement-dependent microcytotoxicity test used for HLA typing.

  6. Immunoscintigraphic detection of infections using monoclonal antigranulocyte antibodies

    International Nuclear Information System (INIS)

    Seybold, K.

    1988-01-01

    We report on a new approach to in vivo labelling of granulocytes for scintigraphic detection of infections by using the I-123 tagged monoclonal anti-CEA antibody-47 (Mab 47). Mab 47 reacts selectively with a glycoprotein (NAC 95) present on the surface of mature granulocytes. Many in vitro tests showed that binding does not inhibit granulocyte functions (e.g. chemotaxis, initiation of 'burst'). Up till now we have performed the search for infectious lesions in 56 patients. For clinical use one dose consisted of 120 mcg Mab 47 labelled with 148-185 MBq I-123 (specific activity: 1.85 GBq/mg). We noticed that all infectious lesions were highly visible 3-6 hours after tracer infusion or could be excluded after 24 h. High counting rates permitted SPECT-studies up to 24 h p.i. which are very usefull for an exact topographic localization of a lesion. The clinical interest was concentrated on cases of bone and joint infections. It is concluded that there are distinct advantages of the new method compared with In-111 WBC scanning. Without the need for cell separation there is a rapid in vivo labelling of granulocytes so that the method is also suitable in very acute cases. No allergic reactions have been observed. In spite of these obvious advantages and the low administered dose of antibodies we recommend a restriction in immunscintigraphy of infections because of the unknown antigenicity of the compound. (orig.) [de

  7. Screening individual hybridomas by microengraving to discover monoclonal antibodies

    Science.gov (United States)

    Ogunniyi, Adebola O; Story, Craig M; Papa, Eliseo; Guillen, Eduardo; Love, J Christopher

    2014-01-01

    The demand for monoclonal antibodies (mAbs) in biomedical research is significant, but the current methodologies used to discover them are both lengthy and costly. Consequently, the diversity of antibodies available for any particular antigen remains limited. Microengraving is a soft lithographic technique that provides a rapid and efficient alternative for discovering new mAbs. This protocol describes how to use microengraving to screen mouse hybridomas to establish new cell lines producing unique mAbs. Single cells from a polyclonal population are isolated into an array of microscale wells (~105 cells per screen). The array is then used to print a protein microarray, where each element contains the antibodies captured from individual wells. The antibodies on the microarray are screened with antigens of interest, and mapped to the corresponding cells, which are then recovered from their microwells by micromanipulation. Screening and retrieval require approximately 1–3 d (9–12 d including the steps for preparing arrays of microwells). PMID:19528952

  8. Application of monoclonal antibodies in diagnostics of the colorectal cancer

    International Nuclear Information System (INIS)

    Mladenov, B.; Milanov, S.; Peshev, N.; Tsanev, Ts.; Minchev, D.; Pencheva, V.

    1991-01-01

    Immunoscintigraphy with CEA monoclonal antibodies (MoA) in patients with colorectal cancer has been applied since 1987 by the authors. MoA from the hybridoma F023C5 are used (IgG 1 -class) and their fragments labelled with 131 I and 111 In. The labelled MoA are introduced intravenously in the course of 30 min, the total activity is 2.5 - 3.5 mCi. The scanning is made 48 and 96 hours on gamma camera. An additional activity on 99m Tc-sulfocolloid and 99m Tc-DTPA is applied for outlining the liver and kidney contours. Digital substraction technique is applied for image processing with contrast and background reduction. The thyroid is blocked with Lugol solution in a course of 5-6 days. Among all of the 18 investigated patients a positive result has been observed in 16. Metastases bigger than 1 cm have a positive scan. No initial invasion in the regional lymph nodes has been established. 3 figs., 4 refs

  9. Development and Evaluation of Monoclonal Antibodies for Paxilline

    Directory of Open Access Journals (Sweden)

    Chris M. Maragos

    2015-09-01

    Full Text Available Paxilline (PAX is a tremorgenic mycotoxin that has been found in perennial ryegrass infected with Acremonium lolii. To facilitate screening for this toxin, four murine monoclonal antibodies (mAbs were developed. In competitive indirect enzyme-linked immunosorbent assays (CI-ELISAs the concentrations of PAX required to inhibit signal development by 50% (IC50s ranged from 1.2 to 2.5 ng/mL. One mAb (2-9 was applied to the detection of PAX in maize silage. The assay was sensitive to the effects of solvents, with 5% acetonitrile or 20% methanol causing a two-fold or greater increase in IC50. For analysis of silage samples, extracts were cleaned up by adsorbing potential matrix interferences onto a solid phase extraction column. The non-retained extract was then diluted with buffer to reduce solvent content prior to assay. Using this method, the limit of detection for PAX in dried silage was 15 µg/kg and the limit of quantification was 90 µg/kg. Recovery from samples spiked over the range of 100 to 1000 µg/kg averaged 106% ± 18%. The assay was applied to 86 maize silage samples, with many having detectable, but none having quantifiable, levels of PAX. The results suggest the CI-ELISA can be applied as a sensitive technique for the screening of PAX in maize silage.

  10. Novel monoclonal autoantibody specificity associated with ribonucleoprotein complexes

    International Nuclear Information System (INIS)

    Winkler, A.; Watson-McKown, R.; Wise, K.

    1986-01-01

    The authors describe an IgG/sub 2a/, kappa monoclonal autoantibody (mAb) F78 derived from a 6-month old MRL-Mp lpr/lpr mouse that recognizes a novel epitope associated with small nuclear ribonuclear protein complexes (snRNP). Indirect immunofluorescent staining of HEp-2 cells with F78 showed a nonnucleolar speckled nuclear pattern characteristic of anti-RNP and anti-Sm mAbs which could be abrogated by pretreating fixed cells with 0.1M HCl prior to staining. Immunoblots of whole cell extracts (dissociated in SDS, urea and mercaptan at 4 0 C then subjected to SDS-PAGE) showed that F78 selectively bound to a component of M/sub r/ = 100,000 clearly distinct from components recognized by two mAbs described by Billings et al that detected, respectively, proteins of M/sub r/ = 70,000 associated with RNP and M/sub r/ = 13,000 associated with Sm. Incubation of extracts at 100 0 C prior to SDS-PAGE eliminated subsequent binding of F78 but not of the other nAbs. F78 as well as the other mAbs selectively immunoprecipitated characteristic patterns of small nuclear RNAs (U 1 , U 2 , U 4 , U 5 , U 6 ) from extracts of 32 P-phosphate labeled HeLa cells. These results suggest a new specificity associated with snRNP that is recognized in the MRL autoimmune response

  11. Epitope Mapping of Monoclonal Antibody PMab-52 Against Cat Podoplanin.

    Science.gov (United States)

    Chang, Yao-Wen; Kaneko, Mika K; Yamada, Shinji; Kato, Yukinari

    2018-02-02

    The mucin-type membrane glycoprotein podoplanin (PDPN) is frequently overexpressed in numerous malignant cancers, including squamous cell carcinoma, germinal neoplasia, mesothelioma, lung cancer, oral cancer, and brain tumor. PDPN expression is strongly associated with cancer progression and poor prognosis. Furthermore, PDPN binds to C-type lectin-like receptor 2 (CLEC-2) on platelets, followed by PDPN-mediated platelet aggregation to facilitate tumor metastasis. We have previously reported a novel anti-cat PDPN (cPDPN) monoclonal antibody (mAb), PMab-52, which specifically detects cPDPN using flow cytometry analysis and successfully identifies cPDPN in feline squamous cell carcinomas. However, the specific binding epitope of cPDPN for PMab-52 remains unelucidated. In this study, a series of deletion or point mutants of cPDPN were utilized for investigating the binding epitopes of PMab-52 using flow cytometry and Western blotting. The findings of this study revealed that the critical epitopes of platelet aggregation-stimulating domain 4 (PLAG4) of cPDPN are responsible for the binding of PMab-52 to cPDPN.

  12. IMMEDIATE REACTIONS TO MONOCLONAL ANTIBODIES IN CLINICAL HEMATOLOGY

    Directory of Open Access Journals (Sweden)

    Vasiliki KYRIAZI

    2016-12-01

    Full Text Available Monoclonal antibodies (MoAbs have been widely used in clinical hematology. As foreign macro-molecules, they can cause infusional reactions during the administration or within 24 hours after the infusion, which encompass a spectrum of mechanisms. Although most of these reactions are non-allergic, are often indistinguishable from true allergic reactions mediated by IgE immunoglobulins. The diagnosis is often challenging and relies mainly on clinical criteria. They occur during the first doses, soon after the initiation of treatment. The symptoms are usually well controlled by the immediate drug discontinuation or reduction of the infusion rate. The management remains largely supportive, consisting of oxygen, intravenous fluids, bronchodilators, antihistamines and steroids. Most of MoAb protocols recommend premedication with steroids and antihistamines and gradually escalating infusion rates. Increased medical and nursing vigilance is required and resuscitative equipment should always be readily available. These events affect patients' quality of life, leading to treatment delay or discontinuation and series of tests. The decision to rechallenge the treatment depends on severity grading, clinical parameters and treatment goals. This article provides an update of MoAbs used in clinical hematology. It summarizes the pathophysiology, the diagnostic approach, the preventive measures and treatment of MoAb-related reactions.

  13. Characterization of Endotrypanum Parasites Using Specific Monoclonal Antibodies

    Directory of Open Access Journals (Sweden)

    Ramos Franco Antonia Maria

    1997-01-01

    Full Text Available A large number of Endotrypanum stocks (representing an heterogeneous population of strains have been screened against a panel of monoclonal antibodies (MAbs derived for selected species of Endotrypanum or Leishmania, to see whether this approach could be used to group/differentiate further among these parasites. Using different immunological assay systems, MAbs considered specific for the genus Endotrypanum (E-24, CXXX-3G5-F12 or strain M6159 of E. schaudinni (E-2, CXIV-3C7-F5 reacted variably according to the test used but in the ELISA or immunofluorescence assay both reacted with all the strains tested. Analyses using these MAbs showed antigenic diversity occurring among the Endotrypanum strains, but no qualitative or quantitative reactivity pattern could be consistently related to parasite origin (i.e., host species involved or geographic area of isolation. Western blot analyses of the parasites showed that these MAbs recognized multiple components. Differences existed either in the epitope density or molecular forms associated with the antigenic determinants and therefore allowed the assignment of the strains to specific antigenic groups. Using immunofluorescence or ELISA assay, clone E-24 produced reaction with L. equatorensis (which is a parasite of sloth and rodent, but not with other trypanosomatids examined. Interestingly, the latter parasite and the Endotrypanum strains cross-reacted with a number of MAbs that were produced against members of the L. major-L. tropica complex

  14. Immunochemical identification of human trophoblast membrane antigens using monoclonal antibodies

    Energy Technology Data Exchange (ETDEWEB)

    Brown, P J; Molloy, C M; Johnson, P M [Liverpool Univ. (UK). Dept. of Immunology

    1983-11-01

    Human trophoblast membrane antigens recognised by monoclonal antibodies (H310, H315, H316 and H317) have been identified using combinations of radioimmunoprecipitation, SDS-PAGE, electroblotting, chromatographic and ELISA-type techniques. H317 is known to identify heat-stable placental-type alkaline phosphatase and accordingly was shown to react with a protein of subunit Msub(r) of 68000. H310 and H316 both recognise an antigen with a subunit Msub(r) of 34000 under reducing conditions. In non-reducing conditions, the H310/316 antigen gave oligomers of a component of Msub(r) 62000. It is unknown whether this 62000 dalton component is a dimer of the 34000 dalton protein with either itself or a second protein chain of presumed Msub(r) around 28000. H315 recognises an antigen with subunit Msub(r) of 36000; in non-reducing conditions this component readily associates to oligomeric structures. The epitope recognised by H315 may be sensitive to SDS. The two proteins recognised by H310/316 and H315 have been termed the p34 and p36 trophoblast membrane proteins, respectively.

  15. Radioiodination of monoclonal antibody intact anti-CEA

    International Nuclear Information System (INIS)

    Okada, H.; Souza, I.T.T.; Silva, C.P.G.

    1990-11-01

    The purpose of this study is to examine a convenient system that can be used to iodinate monoclonal antibodies which is rapid, simple, efficient and reproducible, and which can be accomplished in radiopharmaceutical laboratories. It is important to remember that antibodies are sensitive biochemicals, subject to losses of the activity that is essential to their mode of action, namely the ability to bind specific antigen. The advent of solid phase iodination agents has greatly expanded the range of gentle iodination techniques available for iodinating sensitive biological materials. The agent most widely used is the Iodogen (1,3,4,6 tetrachloro-3a-6a diphenylglycoluril) method. Anti-CEA 4C sub(11) IgG sub(2a,k) (prepared in the Ludwig Institute-Sao Paulo-Brazil ) is used as model to evaluate the Iodogen methodology. The miniature chromatographic system, also rapid, accurate, simple, efficient was elaborated to determine the labelling efficiency incorporation of iodine into immunoglobulin, and the radiochemical purity of sup(131)I-anti-CEA. (author)

  16. [Identification and production of monoclonal antibody of Siberian tiger's immunoglobulin].

    Science.gov (United States)

    Zhang, Yaonglong; Zhang, Duanling; Zhou, Ming; Xue, Yuan; Hua, Yuping; Ma, Jianzhang

    2010-03-01

    To purify immunoglobulin (Ig) of Siberian Tiger and prepare monoclonal antibody (mAb) against the Ig,which can be used to develop immunological diagnostic kits for diagnosing infectious disease in Siberian Tiger. The Ig of Siberian tigers was purified with saturated ammonium sulfate combined with recombinant Protein G. The C57BL/6 mice were immunized with the purified Ig. Spleno-cytes of the mice immunized were collected and fused with the mouse myeloma cell line (Sp2/0-Ag14). The positive hybridoma clones were selected by ELISA and were identified by western blot. The sandwich ELISA was used to detect immunocompetence of the purified Ig and the mAb. We obtained three mouse hybridoma clones that produced mAbs against Ig of Siberian Tiger. The derived McAbs could recognize Ig heavy chain of Siberian Tiger specifically. The biological activity of the Ig and obtained McAbs also could be identified by detecting the antibody induced by panleukopenia virus (FPV-HLJ) vaccine in Siberian Tiger. The antibody also would be useful for assess the vaccine efficacy against the infectious disease on the Siberian Tiger. Protein G can be used in Ig purification of Siberian Tiger. The obtained McAbs from the hybridoma ADT11 in this study owned strong ability to bind Ig of Siberian Tiger and have a stable immunocompetence. They can be used to develop diagnostic methods for detecting infectious disease in Siberian Tiger and vaccine research.

  17. Generation and Application of Monoclonal Antibody Against Lycopene.

    Science.gov (United States)

    Tsibezov, Valeriy V; Bashmakov, Yuriy K; Pristenskiy, Dmitry V; Zigangirova, Naylia A; Kostina, Ludmila V; Chalyk, Natalya E; Kozlov, Alexey Y; Morgunova, Elena Y; Chernyshova, Marina P; Lozbiakova, Marina V; Kyle, Nigel H; Petyaev, Ivan M

    2017-04-01

    A monoclonal antibody (Mab) against lycopene was developed from hybridoma clones obtained from BALB/c mice immunized with trans-isomer of lycopene (t-lycopene, t-LC) conjugated with colloidal gold particles. An alternating immunization schedule which included injection of both formulations of immunogen (without and with Freund's adjuvant) was most effective in the elucidation of a measurable immune response to the t-Lycopene conjugate. Selected hybridoma clones were able to produce an Mab positive in competition assay. In particular, preincubation of 6B9 Mabs with t-LC abolished the ability of 6B9 Mabs to bind LC in the competition assay. Mabs produced by other clones (4F10, 4A3, and 3B12) worked similarly. Analysis of antigen specificity showed that 6B9 Mab raised against t-LC did not recognize other carotenoids such as lutein and carotene. Mab 6B9 was shown to recognize lycopene on a glass surface and in the settings of indirect immunofluorescence experiments performed in cultured hepatocytes and alveolar macrophages incubated with and without lycopene, as well as in sebum and corneocyte specimens from the skin of volunteers supplemented with nutraceutical formulation of lycopene. Newly generated Mabs against lycopene may provide a valuable tool for different analytical assays of lycopene content in various biological, agricultural, and food products.

  18. Production of monoclonal antibodies reactive with ovine eosinophils

    Directory of Open Access Journals (Sweden)

    Meeusen Els NT

    2007-09-01

    Full Text Available Abstract Background There is strong evidence implicating eosinophils in host defence against parasites as well as allergic disease pathologies. However, a lack of reagents such as monoclonal antibodies (mAbs specific for eosinophils has made it difficult to confirm the functional role of eosinophils in such disease conditions. Using an established mammary model of allergic inflammation in sheep, large numbers of inflammatory cells enriched for eosinophils were collected from parasite-stimulated mammary glands and used for the generation of mAbs against ovine eosinophils. Results A panel of mAbs was raised against ovine eosinophils of which two were shown to be highly specific for eosinophils. The reactivity of mAbs 3.252 and 1.2 identified eosinophils from various cell and tissue preparations with no detectable reactivity on cells of myeloid or lymphoid lineage, tissue mast cells, dendritic cells, epithelial cells or other connective tissues. Two other mAbs generated in this study (mAbs 4.4 and 4.10 were found to have reactivity for both eosinophils and neutrophils. Conclusion This study describes the production of new reagents to identify eosinophils (as well as granulocytes in sheep that will be useful in studying the role of eosinophils in disease pathologies in parasite and allergy models.

  19. Biomimetic small peptide functionalized affinity monoliths for monoclonal antibody purification.

    Science.gov (United States)

    Wang, Xiangyu; Xia, Donghai; Han, Hai; Peng, Kun; Zhu, Peijie; Crommen, Jacques; Wang, Qiqin; Jiang, Zhengjin

    2018-08-09

    The rapid development of monoclonal antibodies (mAbs) in therapeutic and diagnostic applications has necessitated the advancement of mAbs purification technologies. In this study, a biomimetic small peptide ligand 3,5-di-tert-butyl-4-hydroxybenzoic acid-Arg-Arg-Gly (DAAG) functionalized monolith was fabricated through a metal ion chelation-based multi-step approach. The resulting monolith showed good chromatographic performance. Compared with the Ni 2+ based IMAC monolith, the DAAG functionalized monolith exhibited not only excellent specificity but also higher dynamic binding capacity (DBC). The 10% DBC and 50% DBC for hIgG reached as high values as 26.0 and 34.6 mg/mL, respectively, at a ligand density of 8.8 μmol/mL, due to the high porosity and accessibility of the monolithic matrix. Moreover, the stability of the DAAG functionalized monolith in successive breakthrough experiments indicates that it has a promising potential for long-term use in mAbs purification. Finally, the DAAG functionalized monolith was successfully applied to the purification of trastuzumab or human immunoglobulin G (hIgG) from biological samples. Copyright © 2018 Elsevier B.V. All rights reserved.

  20. Trimerization Dictates Solution Opalescence of a Monoclonal Antibody.

    Science.gov (United States)

    Yang, Teng-Chieh; Langford, Alex Jacob; Kumar, Sandeep; Ruesch, John Carl; Wang, Wei

    2016-08-01

    Opalescence, sometimes observed in antibody solutions, is thought to be mediated by light scattering of soluble oligomers or insoluble particulates. However, mechanistic features, such as stoichiometry and self-association affinity of oligomeric species related to opalescence, are poorly understood. Here, opalescence behavior of a monoclonal antibody (mAb-1) solution was studied over a wide range of solution conditions including different protein concentrations, pH, and in the presence or absence of salt. Hydrodynamic and thermodynamic properties of mAb-1 solutions were studied by analytical ultracentrifugation and dynamic light scattering. Opalescence in mAb-1 solutions is pH and concentration dependent. The degree of opalescence correlates with reversible monomer-trimer equilibrium detected by analytical ultracentrifugation. Increased trimer formation corresponds to increased opalescence in mAb-1 solutions at higher pH and protein concentrations. Addition of NaCl shifts this equilibrium toward monomer and reduces solution opalescence. This study demonstrates that opalescence in mAb-1 solutions does not arise from the light scattering of monomer or random molecular self-associations but is strongly correlated with a specific self-association stoichiometry and affinity. Importantly, at pH 5.5 (far below isoelectric point of mAb-1), the solution is not opalescent and with nonideal behavior. This study also dissects several parameters to describe the hydrodynamic and thermodynamic nonideality. Copyright © 2016 American Pharmacists Association®. Published by Elsevier Inc. All rights reserved.

  1. Monoclonal antibodies to polioviruses; comparison of intratypic strain differentiation of poliovirus type 1 using monoclonal antibodies versus cross-absorbed antisera.

    NARCIS (Netherlands)

    A.D.M.E. Osterhaus (Albert); A.L. van Wezel; T.G. Hazendonk; F.G.C.M. Uytdehaag (Fons); J.A.A.M. van Asten (Jack); G. van Steenis (Bert)

    1983-01-01

    textabstractA panel of 10 monoclonal antibodies raised to 3 different poliovirus type 1 strains was tested in a micro-enzyme-linked immunosorbent assay and in a micro-neutralization test against 87 poliovirus type 1 strains. The results, evaluated in a newly developed system for intratypic strain

  2. Czech Registry of Monoclonal Gammopathies - Technical Solution, Data Collection and Visualisation.

    Science.gov (United States)

    Brozova, L; Schwarz, D; Snabl, I; Kalina, J; Pavlickova, B; Komenda, M; Jarkovský, J; Němec, P; Horinek, D; Stefanikova, Z; Pour, L; Hájek, R; Maisnar, V

    2017-01-01

    The Registry of Monoclonal Gammopathies (RMG) was established by the Czech Myeloma Group in 2007. RMG is a registry designed for the collection of clinical data concerning diagnosis, treatment, treatment results and survival of patients with monoclonal gammopathies. Data on patients with monoclonal gammopathy of undetermined significance (MGUS), Waldenström macroglobulinaemia (WM), multiple myeloma (MM) or primary AL ("amyloid light-chain") amyloidosis are collected in the registry. Nineteen Czech centres and four Slovak centres currently contribute to the registry. The registry currently contains records on more than 5,000 patients with MM, almost 3,000 patients with MGUS, 170 patients with WM and 26 patients with primary AL amyloidosis, i.e. more than 8,000 records on patients with monoclonal gammopathies altogether. This paper describes technology employed for the collection, storage and subsequent online visualisation of data. The CLADE-IS platform is introduced as a new system for the collection and storage of data from the registry. The form structure and functions of the new system are described for all diagnoses in general; these functions facilitate data entry to the registry and minimise the error rate in data. Publicly available online visualisations of data on patients with MGUS, WM, MM or primary AL amyloidosis from all Czech or Slovak centres are introduced, together with authenticated visualisations of data on patients with MM from selected centres. The RMG represents a data basis that makes it possible to monitor the disease course in patients with monoclonal gammopathies on the population level.Key words: Registry of Monoclonal Gammopathies - RMG - registries - monoclonal gammopathies - CLADE-IS - data visualisation - database.

  3. Radioimmunological imaging of metastatic prostatic cancer with 111indium-labeled monoclonal antibody PAY 276

    International Nuclear Information System (INIS)

    Babaian, R.J.; Murray, J.L.; Lamki, L.M.

    1987-01-01

    A total of 25 patients with histologically proved adenocarcinoma of the prostate, whose disease was staged clinically as D2 by appropriate radiographic and nuclear medicine studies, received increasing doses of PAY 276, an antiprostatic acid phosphatase monoclonal antibody for radioimmunological imaging. The patients were divided into 5 groups of 5. Groups 1 through 5 received an infusion of 5, 10, 20, 40 or 80 mg. monoclonal antibody, respectively, 1 mg. of which was labeled to 5 mCi. of 111 indium, while stable monoclonal antibody was added to achieve the desired antibody concentration. No patient had an allergic reaction, and no significant change in serial hemoglobin levels, platelet count, chemistry profile or results of urinalyses was noted. The monoclonal antibody scan visualized at least 1 lesion in 19 of 25 patients (76 per cent): 4 in groups 1 and 2, and all 15 in groups 3 to 5. With results of conventional radiography and bone scintigraphy considered definitive for metastases, monoclonal antibody scans detected 7 of 32 metastases (21.8 per cent) in group 3 (20 mg.), 31 of 58 (53.4 per cent) in group 4 (40 mg.) and 101 of 134 (75.4 per cent) in group 5 (80 mg). In group 5 the incidence of false positive and false negative scans was 2.3 per cent (3 of 132) and 24.6 per cent (33 of 134), respectively. The detection of metastatic lesions increased as the concentration of unlabeled monoclonal antibody increased. Radioimmunological imaging of prostatic cancer with antiprostatic acid phosphatase monoclonal antibody seems to be feasible

  4. Monoclonal antibody fragment removal mediated by mixed mode resins.

    Science.gov (United States)

    O'Connor, Ellen; Aspelund, Matthew; Bartnik, Frank; Berge, Mark; Coughlin, Kelly; Kambarami, Mutsa; Spencer, David; Yan, Huiming; Wang, William

    2017-05-26

    Efforts to increase monoclonal antibody expression in cell culture can result in the presence of fragmented species requiring removal in downstream processing. Capto adhere, HEA Hypercel, and PPA Hypercel anion exchange/hydrophobic interaction mixed mode resins were evaluated for their fragment removal capabilities and found to separate large hinge IgG1 antibody fragment (LHF) from monomer. Removal of greater than 75% of LHF population occurred at pH 8 and low conductivity. The mechanism of fragment removal was investigated in two series of experiments. The first experimental series consisted of comparison to chromatographic behavior on corresponding single mode resins. Both single mode anion exchange and hydrophobic interaction resins failed to separate LHF. The second experimental series studied the impact of phase modifiers, ethylene glycol, urea, and arginine on the mixed mode mediated removal. The addition of ethylene glycol decreased LHF removal by half. Further decreases in LHF separation were seen upon incubation with urea and arginine. Therefore, it was discovered that the purification is the result of a mixed mode phenomena dominated by hydrophobic interaction and hydrogen bonding effects. The site of interaction between the LHF and mixed mode resin was determined by chemical labeling of lysine residues with sulfo-NHS acetate. The labeling identified the antibody hinge and light chain regions as mediating the fragment separation. Sequence analysis showed that under separation conditions, a hydrophobic proline patch and hydrogen bonding serine and threonine residues mediate the hinge interaction with the Capto adhere ligand. Additionally, a case study is presented detailing the optimization of fragment removal using Capto adhere resin to achieve purity and yield targets in a manufacturing facility. This study demonstrated that mixed mode resins can be readily integrated into commercial antibody platform processes when additional chromatographic abilities

  5. Human monoclonal antibodies reactive with human myelomonocytic leukemia cells.

    Science.gov (United States)

    Posner, M R; Santos, D J; Elboim, H S; Tumber, M B; Frackelton, A R

    1989-04-01

    Peripheral blood mononuclear cells from a patient with chronic myelogenous leukemia (CML), in remission, were depleted of CD8-positive T-cells and cultured with Epstein-Barr virus. Four of 20 cultures (20%) secreted human IgG antibodies selectively reactive with the cell surfaces of certain human leukemia cell lines. Three polyclonal, Epstein-Barr virus-transformed, B-cell lines were expanded and fused with the human-mouse myeloma analogue HMMA2.11TG/O. Antibody from secreting clones HL 1.2 (IgG1), HL 2.1 (IgG3), and HL 3.1 (IgG1) have been characterized. All three react with HL-60 (promyelocytic), RWLeu4 (CML promyelocytic), and U937 (monocytic), but not with KG-1 (myeloblastic) or K562 (CML erythroid). There is no reactivity with T-cell lines, Burkitt's cell lines, pre-B-leukemia cell lines, or an undifferentiated CML cell line, BV173. Leukemic cells from two of seven patients with acute myelogenous leukemia and one of five with acute lymphocytic leukemia react with all three antibodies. Normal lymphocytes, monocytes, polymorphonuclear cells, red blood cells, bone marrow cells, and platelets do not react. Samples from patients with other diverse hematopoietic malignancies showed no reactivity. Immunoprecipitations suggest that the reactive antigen(s) is a lactoperoxidase iodinatable series of cell surface proteins with molecular weights of 42,000-54,000 and a noniodinatable protein with a molecular weight of 82,000. Based on these data these human monoclonal antibodies appear to react with myelomonocytic leukemic cells and may detect a leukemia-specific antigen or a highly restricted differentiation antigen.

  6. Characterization of human monoclonal antibodies that neutralize multiple poliovirus serotypes.

    Science.gov (United States)

    Puligedda, Rama Devudu; Kouiavskaia, Diana; Al-Saleem, Fetweh H; Kattala, Chandana Devi; Nabi, Usman; Yaqoob, Hamid; Bhagavathula, V Sandeep; Sharma, Rashmi; Chumakov, Konstantin; Dessain, Scott K

    2017-10-04

    Following the eradication of wild poliovirus (PV), achieving and maintaining a polio-free status will require eliminating potentially pathogenic PV strains derived from the oral attenuated vaccine. For this purpose, a combination of non-cross-resistant drugs, such as small molecules and neutralizing monoclonal antibodies (mAbs), may be ideal. We previously isolated chimpanzee and human mAbs capable of neutralizing multiple PV types (cross-neutralization). Here, we describe three additional human mAbs that neutralize types 1 and 2 PV and one mAb that neutralizes all three types. Most bind conformational epitopes and have unusually long heavy chain complementarity determining 3 domains (HC CDR3). We assessed the ability of the mAbs to neutralize A12 escape mutant PV strains, and found that the neutralizing activities of the mAbs were disrupted by different amino acid substitutions. Competitive binding studies further suggested that the specific mAb:PV interactions that enable cross-neutralization differ among mAbs and serotypes. All of the cloned mAbs bind PV in the vicinity of the "canyon", a circular depression around the 5-fold axis of symmetry through which PV recognizes its cellular receptor. We were unable to generate escape mutants to two of the mAbs, suggesting that their epitopes are important for the PV life cycle. These data indicate that PV cross-neutralization involves binding to highly conserved structures within the canyon that binds to the cellular receptor. These may be facilitated by the long HC CDR3 domains, which may adopt alternative binding configurations. We propose that the human and chimpanzee mAbs described here could have potential as anti-PV therapeutics. Copyright © 2017 Elsevier Ltd. All rights reserved.

  7. Histone H1(0) mapping using monoclonal antibodies.

    Science.gov (United States)

    Dousson, S; Gorka, C; Gilly, C; Lawrence, J J

    1989-06-01

    Monoclonal antibodies (mAb) to ox liver histone H1 degree were produced and characterized. Two sets of mice were immunized either with pure H1(0) or with an H1(0)-yeast tRNA complex. Eleven hybridomas of various clonal origin were selected. Typing of the antibodies indicated that all but three IgM belonged to the IgG1 class and contained kappa light chains. Immunoblotting experiments using peptides derived from H1(0) or H5 treated by various proteolytic agents (trypsin, N-bromosuccinimide, cyanogen bromide, acetic acid), revealed that nine of the mAb reacted with the globular part of H1(0). More advanced characterization of the antigenic determinants allowed us to determine distinct regions within this globular part which are involved in the antigenic recognition. The peptopes could be subdivided into two groups. Three mAb bound to residues 24-27 and were specific for H1(0). Six mAb bound to residues 27-30 and were specific for H1(0) except one of them which strongly cross-reacted with H5 and GH5. Two mAb reacted with the entire histone H1(0) but failed to react with any of the peptides, suggesting that the corresponding epitope is a conformational antigenic determinant. In order to confirm the localization of the two distinct regions which are involved in the antigenic recognition, a synthetic decapeptide corresponding to the beginning of human H1(0) globular part (from residue 19 to residue 28) was synthesized. Inhibition experiments of the reaction between H1(0) and the various IgG1 mAb by increasing amounts of peptide-bovine serum albumin conjugates were then performed.

  8. Production and characterization of a monoclonal antibody against enrofloxacin.

    Science.gov (United States)

    Chusri, Manaspong; Wongphanit, Pitikarn; Palaga, Tanapat; Puthong, Songchan; Sooksai, Sarintip; Komolpis, Kittinan

    2013-01-01

    Enrofloxacin is a fluoroquinolone antibiotic approved for the treatment of infections in animals. Because of the side effects to consumers of animal products, the maximum residue limits (MRLs) of enrofloxacin in animal tissues for consumption are regulated. In this study, a monoclonal antibody (mAb) against enrofloxacin was prepared and characterized for the development of a direct competitive enzyme-linked immunosorbent assay (ELISA). The obtained mAb, Enro44, was highly specific for enrofloxacin and had a 50% inhibition concentration (IC(50)) of 1.99 ng/ml in a competitive ELISA, and the limit of detection (LOD) was 0.50 ng/ml. The cross-reactivity of the mAb with other quinolones and fluoroquinolones was lower than 0.01%. The subclass of the mAb Enro44 was identified as IgG1. The antigen (Ag)-captured direct competitive ELISA using the mAb Enro44 was tested on different spiked samples, including chicken muscle, cattle milk, and cattle urine, and the assay demonstrated recoveries of 82-112%, 80-125%, and 78-124%, respectively. Furthermore, the quantitation of enrofloxacin obtained from the ELISA and from high-performance liquid chromatography (HPLC) was in good agreement, with the linear regression coefficient between 0.933 and 1.056. The cDNAs encoding a heavy-chain Fd fragment (VH and CH1) and a light chain of the mAb Enro44 were cloned and sequenced. Taken together, the results obtained reveal a potential use of this mAb in an ELISA for the detection of enrofloxacin in food samples. The information of amino acid sequence of this mAb will be useful for further modification and production of the mAb in a bioreactor.

  9. Characterization of a monoclonal antibody to thymidine glycol monophosphate

    International Nuclear Information System (INIS)

    Chen, B.X.; Hubbard, K.; Ide, H.; Wallace, S.S.; Erlanger, B.F.

    1990-01-01

    A monoclonal antibody specific for thymine glycol (TG) in irradiated or OsO4-treated DNA was obtained by immunizing with thymidine glycol monophosphate (TMP-glycol) conjugated to bovine serum albumin by a carbodiimide procedure. Screening by dot-immunobinding and enzyme-linked immunosorbant assay (ELISA) procedures gave eight clones that bound OsO4- treated DNA. One of them, 2.6F.6B.6C, an IgG2a kappa, was characterized further. Hapten inhibition studies with OsO4-treated DNA showed that the antibody was specific for TMP-glycol. Among the various inhibitors tested, inhibition was in the order TMP-glycol greater than 5,6-dihydrothymidine phosphate greater than TMP greater than thymidine glycol greater than TG. Inhibition by 5,6-dihydrothymidine, thymidine, thymine, AMP, and CMP was negligible. In OsO4-treated DNA, as few as 0.5 TG per 10,000 bp were detectable by direct ELISA. Inhibition assays could detect as few as 1.5 TG per 10,000 bp. The antibody was equally reactive with native or denatured DNA containing TG. Among the X-irradiated homopolymers dC, dA, dG, and dT, only dT reacted with the antibody. Using an ELISA, the antibody could detect damage in irradiated DNA at the level of 20 Gy. Thus the antibody is of potential use in assays for DNA damage caused by X rays or other agents that damage DNA by free radical interactions

  10. Safety and immunotoxicity assessment of immunomodulatory monoclonal antibodies

    Science.gov (United States)

    Morton, Laura Dill; Spindeldreher, Sebastian; Kiessling, Andrea; Allenspach, Roy; Hey, Adam; Muller, Patrick Y; Frings, Werner; Sims, Jennifer

    2010-01-01

    Most therapeutic monoclonal antibodies (mAbs) licensed for human use or in clinical development are indicated for treatment of patients with cancer and inflammatory/autoimmune disease and as such, are designed to directly interact with the immune system. A major hurdle for the development and early clinical investigation of many of these immunomodulatory mAbs is their inherent risk for adverse immune-mediated drug reactions in humans such as infusion reactions, cytokine storms, immunosuppression and autoimmunity. A thorough understanding of the immunopharmacology of a mAb in humans and animals is required to both anticipate the clinical risk of adverse immunotoxicological events and to select a safe starting dose for first-in-human (FIH) clinical studies. This review summarizes the most common adverse immunotoxicological events occurring in humans with immunomodulatory mAbs and outlines non-clinical strategies to define their immunopharmacology and assess their immunotoxic potential, as well as reduce the risk of immunotoxicity through rational mAb design. Tests to assess the relative risk of mAb candidates for cytokine release syndrome, innate immune system (dendritic cell) activation and immunogenicity in humans are also described. The importance of selecting a relevant and sensitive toxicity species for human safety assessment in which the immunopharmacology of the mAb is similar to that expected in humans is highlighted, as is the importance of understanding the limitations of the species selected for human safety assessment and supplementation of in vivo safety assessment with appropriate in vitro human assays. A tiered approach to assess effects on immune status, immune function and risk of infection and cancer, governed by the mechanism of action and structural features of the mAb, is described. Finally, the use of immunopharmacology and immunotoxicity data in determining a minimum anticipated biologic effect Level (MABEL) and in the selection of safe human

  11. Effect on renal function of an iso-osmolar contrast agent in patients with monoclonal gammopathies

    International Nuclear Information System (INIS)

    Preda, Lorenzo; Agazzi, Alberto; Martinelli, Giovanni; Raimondi, Sara; Lanfranchi, Carla Federica; Passerini, Rita; Calvetta, Albania; Bellomi, Massimo

    2011-01-01

    To assess the safety of the non-ionic iso-osmolar contrast agent iodixanol on renal function in patients with monoclonal gammopathies undergoing CT. We explored the effect of iodixanol on renal function in 30 patients with monoclonal gammopathies and 20 oncological patients with a normal electrophoretic profile (control group). The parameters used to estimate renal function were: serum creatinine, eGFR (determined 24 h before and 48 h after the administration of iodixanol), and urinary excretion of Neutrophil Gelatinase-Associated Lipocalin (NGAL) determined 2 h and 24 h after. Serum creatinine was also determined 1 month after the administration of iodixanol. No significant increase in serum creatinine values were observed in the monoclonal gammopathies group and in 19/20 patients in the control group. Only 1 patient in the control group developed a transient contrast agent-induced nephropathy. We found no statistically significant difference between the two groups regarding the percentage variation from baseline values of serum creatinine, creatinine clearance, NGAL 2 h after, and eGFR. Whereas NGAL at 24 h showed a statistically significant increase in patients with Monoclonal gammopathies. The use of iodixanol appears to be safe in patients with monoclonal gammopathies and an eGFR ≥ 60 ml/min/1.73 mq. (orig.)

  12. Development of a monoclonal-based enzyme-linked immunoassay for saxitoxin-induced protein.

    Science.gov (United States)

    Smith, D S; Kitts, D D

    1994-03-01

    A monoclonal antibody was generated against saxitoxin-induced protein (SIP) from the small shore crab Hemigrapsus oregenesis. SIP was induced by saxitoxin injection and could be detected in the crude crab extracts with both polyclonal and monoclonal antibody preparations. On Western blots, the polyclonal serum reacted against several bands which were induced by saxitoxin in the crude extracts. These bands represented proteins related to SIP. The monoclonal (4G5), however, was specific for the 79,000 mol. wt subunit of SIP. A triple antibody sandwich ELISA was developed in which polyclonal anti-SIP IgG was used as a trapping layer and monoclonal 4G5 was used as the detection layer. This assay was shown to be more specific and more accurate than a direct bind assay which employed the polyclonal antiserum alone. Although the polyclonal serum was more sensitive than the monoclonal on Western blots, the triple antibody sandwich and direct bind ELISAs were of comparable sensitivity.

  13. Human peripheral blood monocytes display surface antigens recognized by monoclonal antinuclear antibodies

    International Nuclear Information System (INIS)

    Holers, V.M.; Kotzin, B.L.

    1985-01-01

    The authors used monoclonal anti-nuclear autoantibodies and indirect immunofluorescence to examine normal human peripheral blood mononuclear leukocytes for the presence of cell surface nuclear antigens. Only one monoclonal anti-histone antibody (MH-2) was found to bind to freshly isolated PBL, staining approximately 10% of large cells. However, after cells were placed into culture for 16-24 h, a high percentage (up to 60%) of large-sized cells were recognized by an anti-DNA (BWD-1) and several different antihistone monoclonal antibodies (BWH-1, MH-1, and MH-2). These antibodies recognize separate antigenic determinants on chromatin and histones extracted from chromatin. The histone antigen-positive cells were viable, and the monoclonal antibodies could be shown to be binding to the cell surface and not to the nucleus. Using monoclonal antibodies specific for monocytes and T cells, and complement-mediated cytotoxicity, the cells bearing histone antigens were shown to be primarily monocytes. The appearance of histone and DNA antigen-positive cells was nearly completely inhibited by the addition of low concentrations of cycloheximide at initiation of the cultures. In contrast, little effect on the percentage of positive cells was detected if cells were exposed to high doses of gamma irradiation before culture. These data further support the existence of cell surface nuclear antigens on selected cell subsets, which may provide insight into the immunopathogenesis of systemic lupus erythematosus and related autoimmune diseases

  14. Targetted localisation and imaging of a murine lymphoma using 131I-labelled monoclonal antibody

    International Nuclear Information System (INIS)

    Subbiah, Krishnan; Rayala, Suresh Kumar; Ananthanarayanan, Meenakshi; Thangarajan, Rajkumar

    2001-01-01

    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. 131I -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. (author)

  15. LIPOPOLYSACCHARIDE INDUCES THE PRODUCTION OF DIAGNOSTIC MONOCLONAL ANTIBODY BY HYBRIDOMA CELLS AGAINST CONGENITAL ADRENAL HYPERPLASIA

    Directory of Open Access Journals (Sweden)

    GEK KEE CHUA

    2017-11-01

    Full Text Available The purpose of this research is to screen and identify the potential inducers in maximizing the production of monoclonal antibody by hybridoma 192 cell line for Congenital Adrenal Hyperplasia diagnostic. There are nine inducers used in this research, namely lysozyme, aldolase, sodium butyrate, sodium phosphate, potassium phosphate, dimethyl sulfoxide, lipopolysaccharide, essential amino acids, and nonessential amino acids. Hybridoma 192 cell was cultured in 5% CO2 incubator at 37°C and ˃80% humidity in the medium with different concentrations of inducer agents. The inducers were added at the beginning of the culture and the samples were taken after 72 h of culture. The performance of these inducer agents was assessed based on the maximum monoclonal antibody titer achieved using Enzyme-linked Immunosorbent Assay. Lipopolysaccharide was found to increase the maximum monoclonal antibody titer when supplemented at 8 to 12 µg/mL. After optimization using one-factor central composite design at this range, the optimum point was determined to be 8 µg/mL. Verification experiments shows that lipopolysaccharide enhanced the average specific monoclonal antibody production rate by 56% relative to control. In conclusion, lipopolysaccharide at 8 µg/mL is able to increase the monoclonal antibody specific production of hybridoma 192 cell line.

  16. Demonstration of two distinct antigenic determinants on hepatitis B e antigen by monoclonal antibodies

    International Nuclear Information System (INIS)

    Imai, M.; Nomura, M.; Gotanda, T.; Sano, T.; Tachibana, K.; Miyamoto, H.; Takahashi, K.; Toyama, S.; Miyakawa, Y.; Mayumi, M.

    1982-01-01

    Mice were immunized against hepatitis B e antigen (HBeAg) isolated from sera of asymptomatic carriers of hepatitis B virus. Their spleen cells were fused with mouse myeloma (NS-1) cells, and 5 clones of hybridoma cells secreting antibody against HBeAg (anti-HBe) were isolated. For the production of anti-HBe in large scale, cells were cultivated both in vitro and in the peritoneal cavity of ascitic mice. Although monoclonal antibodies produced by these clones showed a strong reactivity of anti-HBe in hemagglutination tests, individual monoclonal anti-HBe did not reveal any precipitin line in immunodiffusion. When 2 of the 5 monoclonal antibodies were mixed together, however, some combinations showed a precipitin line against HBeAg, whereas others did not. Utilizing solid-phase radioimmunoassay involving a number of combinations of monoclonal antibodies used for solid-phase and radiolabeling, the 5 antibodies were classified into 2 groups. Three of the anti-HBe antibodies were found to be directed to 1 determinant of HBeAg (determinant a); the remaining 2 to the other determinant (determinant b). Determinants a and b were detected on HBeAg in the serum, as well as on the polypeptide of 19,000 daltons (P19) derived from the nucleocapsid of hepatitis B virus. Monoclonal anti-HBe antibodies with different specificities may provide useful tools in delineating the antigenic structure of HBeAg and also in evaluating immune responses of the host directed to its subdeterminants

  17. Management of Patients With Hepatitis C Virus, Monoclonal Gammopathy of Undetermined Significance, and Multiple Myeloma

    Directory of Open Access Journals (Sweden)

    Alisse Hannaford BS

    2017-04-01

    Full Text Available Background and Aim: The vast majority of the 2.7 million individuals in the United States who are currently infected with hepatitis C virus (HCV were born between 1945 and 1965. The median age of these patients in this particular generation at the time of this writing was 55 years. In the general population, older age is a risk factor for multiple myeloma (MM and other monogammopathies. As the baby boomer population ages, HCV providers are increasingly likely to encounter HCV-infected patients with a monoclonal gammopathy. Guidelines for managing these patients are needed. Methods: We conducted a detailed case series investigation of 4 HCV-positive patients with MM or a monoclonal gammopathy disorder. Patients were followed at the Mount Sinai Faculty Practice liver clinic. We also performed a detailed review of the literature exploring if there is any known association between HCV, MM, and monoclonal gammopathy. Results and Conclusions: There is no convincing evidence of a causal association between HCV and MM. HCV is linked to type II and type III cryoglobulinemia, specific kinds of monoclonal gammopathies of determinable significance. Whether a link exists between HCV and MM or monoclonal gammopathy of undetermined significance is unclear. Our case series provides the first evidence that modern HCV treatments with direct-acting antivirals can be safely and effectively co-administered with MM chemotherapy.

  18. Using anti-VEGF monoclonal antibody and magnetic nanoparticles

    International Nuclear Information System (INIS)

    Chen Jing; Wuhua; Hang Deyan; Xie Changsheng

    2004-01-01

    Objective: To study the biodistribution of 131 I-anti-vascular endothelial growth factor (VEGF) monoclonal antibody (Sc-7269)-dextran magnetic nanoparticles (DMN) in nude mice bearing human liver cancer where an external magnetic field was focused on, and to evaluate its therapeutic effects and safety. Methods: Eighteen nude mice bearing human liver cancer where an external magnetic field was focused on, were used for the bio-distribution study after intratumoral injection (n=9) or intravenous injection (n=9) of 131 I-Sc-7269-DMN. Another 25 tumor-bearing nude mice were divided into five groups, four groups of them were treated with 74 MBq/ml 131 I-Sc-7269-DMN, 131 I-Sc-7269, 131 I-DMN and 131 I by a single intratumoral injection, respectively. And an external magnetic field was bound to the tumor of the nude mice that were injected 131 I-Sc-7269-DMN or 131 I-DMN. For control study, the remaining one group was injected with physiological saline. Tumor growth delay (TGD) and tumor inhibition rate were observed as antitumor effects. Peripheral white cell counts and the loss of body weight were tested as indicators of systemic toxicity. Results: The retention percentages of radioactivity (%ID/g) in tumors after intratumoral injection were 104.06, 101.58 and 100.96%ID/g at 4, 24 and 48 h, respectively, while in the case of intravenous injection, the %ID/g values were lower (85.33, 89.67 and 90.00%ID/g, respectively, P 131 I-Sc-7269-DMN [ (13.3 ± 3.3) d] was the longest, and tumor inhibition rate (89.0%)was the highest compared with that in other groups (P 131 I-Sc-7269-DMN-treated mice as monitored by the decrease in peripheral white cell counts and the loss of body weight. Conclusions: The radioimmunotherapy with intratumoral injection of 131 I-Sc-7269-DMN may be safe and efficient for the treatment of liver cancer. Furthermore, the radioimmunotherapy using DMN as a carrier system may be a highly potential approach in targeted treatment of other kinds of tumors

  19. Exploration of overloaded cation exchange chromatography for monoclonal antibody purification.

    Science.gov (United States)

    Liu, Hui F; McCooey, Beth; Duarte, Tiago; Myers, Deanna E; Hudson, Terry; Amanullah, Ashraf; van Reis, Robert; Kelley, Brian D

    2011-09-28

    Cation exchange chromatography using conventional resins, having either diffusive or perfusive flow paths, operated in bind-elute mode has been commonly employed in monoclonal antibody (MAb) purification processes. In this study, the performance of diffusive and perfusive cation exchange resins (SP-Sepharose FF (SPSFF) and Poros 50HS) and a convective cation exchange membrane (Mustang S) and monolith (SO(3) Monolith) were compared. All matrices were utilized in an isocratic state under typical binding conditions with an antibody load of up to 1000 g/L of chromatographic matrix. The dynamic binding capacity of the cation exchange resins is typically below 100 g/L resin, so they were loaded beyond the point of anticipated MAb break through. All of the matrices performed similarly in that they effectively retained host cell protein and DNA during the loading and wash steps, while antibody flowed through each matrix after its dynamic binding capacity was reached. The matrices differed, though, in that conventional diffusive and perfusive chromatographic resins (SPSFF and Poros 50HS) demonstrated a higher binding capacity for high molecular weight species (HMW) than convective flow matrices (membrane and monolith); Poros 50HS displayed the highest HMW binding capacity. Further exploration of the conventional chromatographic resins in an isocratic overloaded mode demonstrated that the impurity binding capacity was well maintained on Poros 50HS, but not on SPSFF, when the operating flow rate was as high as 36 column volumes per hour. Host cell protein and HMW removal by Poros 50HS was affected by altering the loading conductivity. A higher percentage of host cell protein removal was achieved at a low conductivity of 3 mS/cm. HMW binding capacity was optimized at 5 mS/cm. Our data from runs on Poros 50HS resin also showed that leached protein A and cell culture additive such as gentamicin were able to be removed under the isocratic overloaded condition. Lastly, a MAb

  20. Advantage of dose fractionation in monoclonal antibody-targeted radioimmunotherapy

    International Nuclear Information System (INIS)

    Schlom, J.; Molinolo, A.; Simpson, J.F.; Siler, K.; Roselli, M.; Hinkle, G.; Houchens, D.P.; Colcher, D.

    1990-01-01

    Monoclonal antibody (MAb) B72.3 IgG was radiolabeled with 131I and administered to female athymic NCr-nu mice bearing the LS-174T human colon adenocarcinoma xenograft to determine if fractionation of MAb dose had any advantage in tumor therapy. In the LS-174T xenograft, only approximately 30%-60% of tumor cells express the B72.3-reactive TAG-72 antigen. The LS-174T xenograft was used to reflect the heterogeneity of the TAG-72 antigen often seen in biopsy specimens from patients. In contrast to a single 600-muCi dose of 131I-B72.3 IgG where 60% of the animals died from toxic effects, two 300-muCi doses of 131I-B72.3 IgG reduced or eliminated tumor growth in 90% of mice, with only 10% of the animals dying from toxic effects. Dose fractionation even permitted escalation of the dose to three doses of 300 muCi of 131I-B72.3 IgG, resulting in even more extensive tumor reduction or elimination and minimal toxic effects. The use of an isotype-matched control MAb revealed a nonspecific component to tumor growth retardation, but the use of the specific B72.3 IgG demonstrated a much greater therapeutic effect. Tumors that had escaped MAb therapy were analyzed for expression of the B72.3-reactive TAG-72 antigen with the use of the immunoperoxidase method; they were shown to have the same antigenic phenotype as the untreated tumors. We verified tumor elimination by killing the test animals after a 7-week observation period and performing histologic examination of tumor sites. We also monitored toxic effects by histologic examination of numerous organs. These studies thus demonstrate the advantage of dose fractionation of a radiolabeled MAb for tumor therapy. We anticipate that the concept of dose fractionation can be practically applied in radioimmunotherapeutic clinical trials with the development and use of recombinant-chimeric MAbs and modified constructs

  1. Improved radioimaging and tumor localization with monoclonal F(ab')2

    International Nuclear Information System (INIS)

    Wahl, R.L.; Parker, C.W.; Philpott, G.W.

    1983-01-01

    Monoclonal anti-tumor antibodies have great promise for radioimmunodetection and localization of tumors. Fab and F(ab')2 fragments, which lack the Fc fragment of antibody (Ab), are cleared more rapidly from the circulation and may have less nonspecific tissue binding than intact Ab. In radioimaging studies using a murine monoclonal antibody to carcinoembryonic antigen in a human colon carcinoma xenografted into hamsters, F(ab')2 fragments were shown superior to Fab fragments and intact antibody for scintiscanning. In double-label experiments with anti-CEA antibody and control monoclonal IgG, F(ab')2 fragments were found to give better and more rapid specific tumor localization than intact antibody or Fab fragments. F(ab')2 fragments offer significant promise for tumor imaging and possibly therapy

  2. High-affinity monoclonal antibodies specific for deoxynucleosides structurally modified by alkylating agents: Applications for immunoanalysis

    International Nuclear Information System (INIS)

    Adamkiewicz, J.; Ahrens, O.; Rajewsky, M.F.

    1984-01-01

    So far the results of attempts to use monoclonal antibodies for the demonstration of carcinogen-DNA adducts in cells by immunostaining have been promising. Thus the authors have established a standardized procedure for the quantitation of specific alkyl-deoxynucleosides in the nuclear DNA of individual cells by direct immunofluorescence, using tetramethylrhodamine isothiocyanate-labeled monoclonal antibodies and a computer-based image analysis of electronically intensified fluorescence signals. With a fluorescent anti-(O/sup 6/-EtdGuo) monoclonal antibody, the present detection limit for O/sup 6/-Etd-Guo in the nuclei of individual cells previously exposed to an ethylating N-nitroso compound (e.g., N-ethyl-N-nitrosourea) is -- 700 O/sup 6/-EtdGuo molecules per diploid genome, i.e., similar to the detection limit for the same ethylation product in a hydrolysate of (O/sup 6/-EtdGuo)-containing DNA analyzed by competitive RIA

  3. Use of radiolabeled monoclonal anti-B1 antibody for B lymphocyte imaging in Rhesus monkeys

    International Nuclear Information System (INIS)

    Letvin, N.L.; Zalutsky, M.R.; Chalifoux, L.V.; Atkins, H.L.

    1987-01-01

    Imaging tissues rich in B lymphocytes in man using a radiolabeled monoclonal anti-B cell antibody would be extremely useful in the clinical staging of non-Hodgkins lymphomas. Studies were done in rhesus monkeys using radiolabeled monoclonal anti-B1 antibody to determine the feasibility of such an approach. Immunohistologic studies demonstrated that infused monoclonal anti-B1 binds in vivo with specificity to B cells in lymph nodes and spleen. The kinetics of clearance of 131 I-labeled anti-B1 were determined. The B lymphocyte-rich spleen could be readily visualized by gamma camera scanning without significant background and without the need for image intensification or blood background subtraction techniques. These data support the feasibility of using anti-B1 for staging B cell lymphomas in man. (author)

  4. [Monoclonal antibodies ICO-02 to blast cell antigens in patients with chronic myeloleukemia in blast crisis].

    Science.gov (United States)

    Baryshnikov, A Iu

    1984-01-01

    Mice were immunized with blood cells of a patient with chronic granulocytic leukemia, and their cells were subsequently used for the preparation of hybridoma ICO-02. This hybridoma is continuously producing monoclonal antibodies which reacted with cells in 4 out of 13 patients with blastic crisis of chronic granulocytic leukemia and in 6 out of 38 patients with acute lymphoblastic leukemia. Antibodies reacted with blast cells in 2 out of 3 patients with undifferentiated blastic crisis of chronic myelocytic leukemia and in 2 out of 5 patients with lymphoid variant of blastic crisis of chronic granulocytic leukemia. Cells of 6 patients with acute lymphoblastic leukemia which reacted with the monoclonal antibodies had immunological markers of T lymphocytes bone-marrow precursors. Monoclonal antibodies did not react with cells of blood and bone marrow from healthy people and from patients with chronic lymphocytic leukemia, acute myeloblastic leukemia, acute myelomonocytic leukemia, acute monoblastic leukemia and lymphosarcoma.

  5. Radiolabeled monoclonal antibodies for imaging and therapy: Potential, problems, and prospects: Scientific highlights

    International Nuclear Information System (INIS)

    Srivastava, S.C.; Buraggi, G.L.

    1986-01-01

    This meeting focused on areas of research on radiolabeled monoclonal antibodies. Topics covered included the production, purification, and fragmentation of monoclonal antibodies and immunochemistry of hybridomas; the production and the chemistry of radionuclides; the radiohalogenation and radiometal labeling techniques; the in-vivo pharmacokinetics of radiolabeled antibodies; the considerations of immunoreactivity of radiolabeled preparations; the instrumentation and imaging techniques as applied to radioimmunodetection; the radiation dosimetry in diagnostic and therapeutic use of labeled antibodies; the radioimmunoscintigraphy and radioimmunotherapy studies; and perspectives and directions for future research. Tutorial as well as scientific lectures describing the latest research data on the above topics were presented. Three workshop panels were convened on ''Methods for Determining Immunoreactivity of Radiolabeled Monoclonal Antibodies - Problems and Pitfalls,'' Radiobiological and Dosimetric Considerations for Immunotherapy with Labeled Antibodies,'' and ''The Human Anti-Mouse Antibody Response in Patients.''

  6. Comparative tumour localization properties of radiolabelled monoclonal antibody preparations of defined immunoreactivities

    International Nuclear Information System (INIS)

    Pimm, M.V.; Baldwin, R.W.

    1987-01-01

    The immunoreactive fraction of an anti-CEA monoclonal antibody preparation has been progressively decreased by the addition of increasing proportions of impurity in the form of immunologically inert mouse immunoglobulin. Following radioiodination, the immunoreactive fractions of the preparations were determined and their localization in a human tumour xenograft in nude mice was assessed. There was a progressive decline in tumour localization, from tumour to blood ratios of 2:1 with unadulterated antibody to 0.6:1 with preparations only 15% with respect to the initial antibody. These findings demonstrate that the immunoreactive fraction of monoclonal antibody preparations is a major limiting factor in tumour localization and this has implications for experimental and clinical applications of monoclonal antibodies. (orig.)

  7. Production and characterization of monoclonal antibodies to the edta extract of Leptospira interrogans, serovar icterohaemorrhagiae

    Directory of Open Access Journals (Sweden)

    Lilian Terezinha de Queiroz Leite

    1996-10-01

    Full Text Available Monoclonal antibodies (MABs ivere produced against an etbylenediaminetetraacetate (EDTA extract of Leptospira interrogans serovar icterohaemorrhagiae being characterized by gel precipitation as IgM and IgG (IgGl and IgG2b. The EDTA extract was detected as several bands by silver staining in SDS-PAGE. In the Western blot the bands around 20 KDa reacted with a monoclonal antibody, 47B4D6, and was oxidized by periodate and was not digested by pronase, suggesting that the determinant is of carbohydrate nature, lmmunocytochemistry, using colloidal gold labeling, showed that an EDTA extract determinant recognized by monoclonal antibody 47B4D6, is localized under the outer envelope of serovar icterohaemorrhagiae. Hoe AIAB raised against the EDTA extract was not able to protect hamsters from lethal challenge with virulent homologous leptospires.

  8. The development of methods for obtaining monoclonal antibody-producing cells

    Directory of Open Access Journals (Sweden)

    Michał Skowicki

    2016-04-01

    Full Text Available Monoclonal antibodies (mAbs are biomolecules of great scientific and practical significance. In contrast to polyclonal antibodies from immune sera, they are homogeneous and monospecific, since they are produced by hybridoma cells representing a clone arising from a single cell. The successful technology was described for the first time in 1975; the inventors were later awarded the Nobel Prize. Currently, mAbs are broadly used as a research tool, in diagnostics and medicine in particular for the treatment of cancer or in transplantology. About 47 therapeutics based on monoclonal antibodies are now available in the US and Europe, and the number is still growing. Production of monoclonal antibodies is a multistage, time-consuming and costly process. Growing demand for these molecules creates space for research focused on improvements in hybridoma technology. Lower costs, human labor, and time are important goals of these attempts. In this article, a brief review of current methods and their advances is given.

  9. Preparation of Ga-67 labeled monoclonal antibodies using deferoxamine as a bifunctional chelating agent

    International Nuclear Information System (INIS)

    Endo, K.; Furukawa, T.; Ohmomo, Y.

    1984-01-01

    Ga-67 labeled monoclonal IgG or F(ab')/sub 2/ fragments against α-fetoprotein and β-subunit of human choriogonadotropin (HCG), were prepared using Deferoxamine (DFO) as a bifunctional chelating agent. DFO, a well-known iron chelating agent, was conjugated with monoclonal antibodies (Ab) by a glutaraldehyde two step method and the effect of conjugation on the Ab activities was examined by RIA and Scatchard plot analysis. In both monoclonal Ab preparations, the conjugation reaction was favored as the pH increased. However, Ab-binding activities decreased as the molecular ratios of DFO to Ab increased. Preserved Ab activities were observed when Ab contained DFO per Ab molecule less than 2.1. At a ratio of over 3.3 DFO molecules per Ab, the maximal binding capacity rather than the affinity constant decreased. The inter-molecular cross linkage seemed to be responsible for the deactivation of binding activities. The obtained DFO-Ab conjugates, were then easily labeled with high efficiency and reproducibility and Ga-67 DFO-Ab complexes were highly stable both in vitro and in vivo. Thus, biodistribution of Ga-67 labeled F(ab')/sub 2/ fragments of monoclonal Ab to HCG β-subunit was attempted in nude mice transplanted with HCG-producing human teratocarcinoma. Tumor could be visualized, in spite of relatively high background imaging of liver, kidney and spleen. The use of DFO as a bifunctional chelating agent provided good evidence for its applicability to labeling monoclonal Ab with almost full retention of Ab activities. Further, availability of Ga-68 will make Ga-68 DFO-monoclonal Ab a very useful tool for positron tomography imaging of various tumors

  10. Monoclonal protein reference change value as determined by gel-based serum protein electrophoresis.

    Science.gov (United States)

    Salamatmanesh, Mina; McCudden, Christopher R; McCurdy, Arleigh; Booth, Ronald A

    2018-01-01

    The International Myeloma Working Group recommendations for monitoring disease progression or response include quantitation of the involved monoclonal immunoglobulin. They have defined the minimum change criteria of ≧25% with an absolute change of no gel-based serum protein electrophoresis. Sixteen clinically stable MGUS patients were identified from our clinical hematology database. Individual biological variability (CVi) was determined and used to calculate a monoclonal protein reference change value (RCV). Analytical variability of the normal protein fractions (albumin, alpha-1, alpha-2, beta, total gamma) ranged from 1.3% for albumin to 5.8% for the alpha-1 globulins. CVa of low (5.6g/L) and high (32.2g/L) concentration monoclonal proteins were 3.1% and 22.2%, respectively. Individual CVi of stable patients ranged from 3.5% to 24.5% with a CVi of 12.9%. The reference change value (RCV) at a 95% probability was determined to be 36.7% (low) 39.6% (high) using our CVa and CVi. Serial monitoring of monoclonal protein concentration is important for MGUS and multiple myeloma patients. Accurate criteria for interpreting a change in monoclonal protein concentration are required for appropriate decision making. We used QC results and real-world conditions to assess imprecision of serum protein fractions including low and high monoclonal protein fractions and clinically stable MGUS patients to determine CVi and RCV. The calculated RCVs of 36.7% (low) and 39.6% (high) in this study were greater that reported previously and greater than the established criteria for relapse. Response criteria may be reassessed to increase sensitivity and specificity for detection of response. Copyright © 2017 The Canadian Society of Clinical Chemists. Published by Elsevier Inc. All rights reserved.

  11. Monoclonal antibodies to human factor VII: a one step immunoradiometric assay for VII:Ag.

    OpenAIRE

    Takase, T; Tuddenham, E G; Chand, S; Goodall, A H

    1988-01-01

    Three mouse monoclonal antibodies (RFF-VII/1, RFF-VII/2, and RFF-VII/3) which bind specifically to different epitopes on human factor VII antigen were raised. Two of the antibodies, RFF-VII/1 and RFF-VII/2, bound strongly to factor VII antigen (VII:Ag), but only RFF-VII/1 and RFF-VII/3 were potent inhibitors of factor VII coagulation activity (VII:C). RFF-VII/1 and RFF-VII/2 were used in a one step, double monoclonal immunoradiometric assay for VII:Ag. This was highly reproducible and detecte...

  12. Monoclonal antibodies to antigens on human neutrophils, activated T lymphocytes, and acute leukemia blast cells

    International Nuclear Information System (INIS)

    Miterev, G.Yu.; Burova, G.F.; Puzhitskaya, M.S.; Danilevich, S.V.; Bulycheva, T.I.

    1987-01-01

    The authors describe the production of two mouse hybridomas secreting monoclonal antibodies to antigenic determinants of the surface membranes of human neutrophils, activated T lymphocytes, and acute leukemic blast cells. The degree of lymphocyte stimulation was estimated from incorporation of 3 H-thymidine with parallel microculture. Monoclonal antibodies of supernatants of hybridoma cultures shown here reacted in both immunofluorescence test and cytotoxicity test with surface membrane antigens on the majority of neutrophils and PHA-activated peripheral blood lymphocytes from healthy subjects, but did not give positive reactions with unactivated lymphocytes, adherent monocytes, erythrocytes, and alloantigen-stimulated lymphocytes

  13. Monoclonal antibodies to antigens on human neutrophils, activated T lymphocytes, and acute leukemia blast cells

    Energy Technology Data Exchange (ETDEWEB)

    Miterev, G.Yu.; Burova, G.F.; Puzhitskaya, M.S.; Danilevich, S.V.; Bulycheva, T.I.

    1987-11-01

    The authors describe the production of two mouse hybridomas secreting monoclonal antibodies to antigenic determinants of the surface membranes of human neutrophils, activated T lymphocytes, and acute leukemic blast cells. The degree of lymphocyte stimulation was estimated from incorporation of /sup 3/H-thymidine with parallel microculture. Monoclonal antibodies of supernatants of hybridoma cultures shown here reacted in both immunofluorescence test and cytotoxicity test with surface membrane antigens on the majority of neutrophils and PHA-activated peripheral blood lymphocytes from healthy subjects, but did not give positive reactions with unactivated lymphocytes, adherent monocytes, erythrocytes, and alloantigen-stimulated lymphocytes.

  14. Improved detection of Pneumocystis carinii by an immunofluorescence technique using monoclonal antibodies

    DEFF Research Database (Denmark)

    Orholm, M; Holten-Andersen, W; Lundgren, Jens Dilling

    1990-01-01

    To assess whether a recently developed indirect immunofluorescent stain using monoclonal antibodies was more sensitive in detecting Pneumocystis carinii than the combination of Giemsa and methenamine silver nitrate stains which has routinely been used in the laboratory, 88 lavage fluid specimens...... silver nitrate and toluidine blue O. Immunofluorescence using the monoclonal antibodies from the NIH was significantly more sensitive than any other single staining method and than the combination of Giemsa and methenamine silver nitrate staining. The study also showed that the cytospin centrifuge...

  15. Development of Immunoassay Based on Monoclonal Antibody Reacted with the Neonicotinoid Insecticides Clothianidin and Dinotefuran

    OpenAIRE

    Uchigashima, Mikiko; Watanabe, Eiki; Ito, Shigekazu; Iwasa, Seiji; Miyake, Shiro

    2012-01-01

    Enzyme-linked immunosorbent assay (ELISA) based on a monoclonal antibody (MoAb) was developed for the neonicotinoid insecticide clothianidin. A new clothianidin hapten (3-[5-(3-methyl-2-nitroguanidinomethyl)-1,3-thiazol-2-ylthio] propionic acid) was synthesized and conjugated to keyhole limpet hemocyanin, and was used for monoclonal antibody preparation. The resulting MoAb CTN-16A3-13 was characterized by a direct competitive ELISA (dc-ELISA). The 50% of inhibition concentration value with cl...

  16. Localisation of lung cancer by a radiolabelled monoclonal antibody against the c-myc oncogene product

    Energy Technology Data Exchange (ETDEWEB)

    Chan, S Y.T.; Evan, G I; Ritson, A; Watson, J; Wraight, P; Sikora, K

    1986-11-01

    A set of mouse monoclonal antibodies against the c-myc oncogene product, a 62,000 dalton nuclear binding protein involved in cell cycle control, has been constructed by immunisation with synthetic peptide fragments. One such antibody, CT14, was radiolabelled with /sup 131/I and administered to 20 patients with different malignant diseases. Good tumour localisation was observed in 12 out of 14 patients with primary bronchial carcinoma but not in patients with pulmonary metastases from primary tumours elsewhere. Successfully localised tumours were all 3 cm or more in diameter. Monoclonal antibodies against oncogene products may provide novel selective tools for the diagnosis and therapy of cancer.

  17. Clinical prospective study with radioiodinated monoclonal antibodies directed against colorectal cancer

    International Nuclear Information System (INIS)

    Chatal, J.F.; Douillard, J.Y.; Kremer, M.; Curtet, C.; Le Mevel, B.; Saccavini, J.C.; Maurel, C.; Aubry, J.

    1985-01-01

    The diagnostic application of three monoclonal antibodies are studied: an anti-carcinoembryonic antigen (CEA) antibody designated as 202 and two monoclonal antibodies, designated as 17-1A and 19-9, which recognize different antigens associated with gastrointestinal carcinomas. The complementary specificity of these antibodies was determined by an immuno-histochemical study and the scintigraphic detection parameters by a radiopharmacokinetic study in colic-tumour-bearing nude mice. On the basis of a prospective study, the value of immunoscintigraphy was compared with conventional methods such as ultrasonography and computed tomography for localization of recurrences of colorectal cancers. (UK)

  18. Monoclonal Antibody Fragments for Targeting Therapeutics to Growth Plate Cartilage | NCI Technology Transfer Center | TTC

    Science.gov (United States)

    Researchers at The Eunice Kennedy Shriver National Institute on Child Health and Human Development (NICHD) have discovered monoclonal antibodies that bind to matrilin-3, a protein specifically expressed in cartilage tissue, that could be used for treating or inhibiting growth plate disorders, such as a skeletal dysplasia or short stature. The monoclonal antibodies can also be used to target therapeutic agents, such as anti-arthritis agents, to cartilage tissue. NICHD seeks statements of capability or interest from parties interested in collaborative research to co-develop, evaluate, or commercialize treatment of skeletal disorders using targeting antibodies.

  19. Development of a monoclonal antibody against viral haemorrhagic septicaemia virus (VHSV) genotype IVa

    DEFF Research Database (Denmark)

    Ito, T.; Olesen, Niels Jørgen; Skall, Helle Frank

    2010-01-01

    of the spread of genotypes to new geographical areas. A monoclonal antibody (MAb) against VHSV genotype IVa was produced, with the aim of providing a simple method of discriminating this genotype from the other VHSV genotypes (I, II, III and IVb). Balb/c mice were injected with purified VHSV-JF00Ehil (genotype...... IVa) from diseased farmed Japanese flounder. Ten hybridoma clones secreting monoclonal antibodies (MAbs) against VHSV were established. One of these, MAb VHS-10, reacted only with genotype IVa in indirect fluorescent antibody technique (IFAT) and ELISA. Using cell cultures that were transfected...

  20. Pneumocystis carinii and specific fungi have a common epitope, identified by a monoclonal antibody

    DEFF Research Database (Denmark)

    Lundgren, B; Kovacs, J A; Nelson, N N

    1992-01-01

    Because Pneumocystis carinii may be related to fungi, we evaluated the reactivities of monoclonal antibodies raised against P. carinii with a variety of fungi. Fifty-two fungi and six protozoa were evaluated by immunofluorescence. One of three monoclonal antibodies (MAbs) tested (MAb 7D7) reacted...... with 15 fungi but no protozoa. Saccharomyces cerevisiae showed the strongest reactivity by immunofluorescence. The reactive antigen was characterized for four fungi by the immunoblot technique. In all cases the antigen that was reactive with MAb 7D7 was larger than the P. carinii antigens that reacted...

  1. Daratumumab: a first-in-class CD38 monoclonal antibody for the treatment of multiple myeloma

    Directory of Open Access Journals (Sweden)

    Larysa Sanchez

    2016-06-01

    Full Text Available Abstract Daratumumab is a human monoclonal antibody that targets CD38, a cell surface protein that is overexpressed on multiple myeloma (MM cells. Preclinical studies have shown that daratumumab induces MM cell death through several mechanisms, including complement-dependent cytotoxicity (CDC, antibody-dependent cell-mediated cytotoxicity (ADCC, antibody-dependent cellular phagocytosis (ADCP, and apoptosis. Given the encouraging efficacy and acceptable safety profile of daratumumab demonstrated in clinical trials, daratumumab has emerged as a novel treatment option for myeloma and became the first monoclonal antibody approved by the FDA for the treatment of MM.

  2. Approaches to lung cancer treatment using the CD3E x GP-2-directed bispecific monoclonal antibody BIS-1

    NARCIS (Netherlands)

    Kroesen, BJ; Nieken, J; Sleijfer, DT; Molema, G; deVries, EGE; Groen, HJM; Helfrich, W; The, TH; Mulder, NH; deLeij, L

    1997-01-01

    The bispecific monoclonal antibody (bsAb) BIS-1 combines a monoclonal-antibody(mAb)-defined specificity for the CD3 complex, as present on all T lymphocytes, with a mAb-defined specificity for the pancarcinoma/epithelium associated glycoprotein EGP-2. In vitro studies indicate that BIS-1 can direct

  3. Development of an analytical method to assess the occupational health risk of therapeutic monoclonal antibodies using LC-HRMS.

    Science.gov (United States)

    Reinders, Lars M H; Klassen, Martin D; Jaeger, Martin; Teutenberg, Thorsten; Tuerk, Jochen

    2018-04-01

    Monoclonal antibodies are a group of commonly used therapeutics, whose occupational health risk is still discussed controversially. The long-term low-dose exposure side effects are insufficiently evaluated; hence, discussions are often based on a theoretical level or extrapolating side effects from therapeutic dosages. While some research groups recommend applying the precautionary principle for monoclonal antibodies, others consider the exposure risk too low for measures taken towards occupational health and safety. However, both groups agree that airborne monoclonal antibodies have the biggest risk potential. Therefore, we developed a peptide-based analytical method for occupational exposure monitoring of airborne monoclonal antibodies. The method will allow collecting data about the occupational exposure to monoclonal antibodies. Thus, the mean daily intake for personnel in pharmacies and the pharmaceutical industry can be determined for the first time and will help to substantiate the risk assessment by relevant data. The introduced monitoring method includes air sampling, sample preparation and detection by liquid chromatography coupled with high-resolution mass spectrometry of individual monoclonal antibodies as well as sum parameter. For method development and validation, a chimeric (rituximab), humanised (trastuzumab) and a fully humanised (daratumumab) monoclonal antibody are used. A limit of detection between 1 μg per sample for daratumumab and 25 μg per sample for the collective peptide is achieved. Graphical abstract Demonstration of the analytical workflow, from the release of monoclonal antibodies to the detection as single substances as well as sum parameter.

  4. Data on the characterization of follicle-stimulating hormone monoclonal antibodies and localization in Japanese eel pituitary

    Directory of Open Access Journals (Sweden)

    Dae-Jung Kim

    2016-09-01

    Full Text Available Monoclonal antibodies were generated against recombinant follicle-stimulating hormone (rec-FSH from Japanese eel Anguilla japonica; rec-FSH was produced in Escherichia coli and purified using Ni-NTA Sepharose column chromatography.In support of our recent publication, ''Production and characterization of monoclonal antibodies against recombinant tethered follicle-stimulating hormone from Japanese eel Anguilla japonica'' [1], it was important to characterize the specificity of eel follicle-stimulating hormone antibodies. Here, the production and ELISA system of these monoclonal antibodies are presented. The affinity-purified monoclonal antibodies specifically detected eel rec-FSH in ELISA and on western blots of rec-FSH produced from CHO cells. Immunohistochemical analysis revealed that FSH staining was specifically localized in the eel pituitary. Keywords: Japanese eel, FSH, Monoclonal Antibody

  5. Large Scale Generation and Characterization of Anti-Human IgA Monoclonal Antibody in Ascitic Fluid of Balb/c Mice

    OpenAIRE

    Fatemeh Ezzatifar; Jafar Majidi; Behzad Baradaran; Leili Aghebati Maleki; Jalal Abdolalizadeh; Mehdi Yousefi

    2015-01-01

    Purpose: Monoclonal antibodies are potentially powerful tools used in biomedical research, diagnosis, and treatment of infectious diseases and cancers. The monoclonal antibody against Human IgA can be used as a diagnostic application to detect infectious diseases. The aim of this study was to improve an appropriate protocol for large-scale production of mAbs against IgA. Methods: For large-scale production of the monoclonal antibody, hybridoma cells that produce monoclonal antibodies again...

  6. Large Scale Generation and Characterization of Anti-Human CD34 Monoclonal Antibody in Ascetic Fluid of Balb/c Mice

    OpenAIRE

    Aghebati Maleki, Leili; Majidi, Jafar; Baradaran, Behzad; Abdolalizadeh, Jalal; Kazemi, Tohid; Aghebati Maleki, Ali; Sineh sepehr, Koushan

    2013-01-01

    Purpose: Monoclonal antibodies or specific antibodies are now an essential tool of biomedical research and are of great commercial and medical value. The purpose of this study was to produce large scale of monoclonal antibody against CD34 in order to diagnostic application in leukemia and purification of human hematopoietic stem/progenitor cells. Methods: For large scale production of monoclonal antibody, hybridoma cells that produce monoclonal antibody against human CD34 were injected into t...

  7. 75 FR 3244 - Prospective Grant of Exclusive License: Monoclonal Antibodies Against Smallpox/Orthopoxviruses

    Science.gov (United States)

    2010-01-20

    ... Exclusive License: Monoclonal Antibodies Against Smallpox/Orthopoxviruses AGENCY: National Institutes of.... SUPPLEMENTARY INFORMATION: Concerns that variola (smallpox) virus might be used as a biological weapon have led... safe and effective for prevention of smallpox, it is well documented that various adverse reactions in...

  8. Monoclonal Antibodies for Non-Hodgkin's Lymphoma: State of the Art and Perspectives

    Directory of Open Access Journals (Sweden)

    Giulia Motta

    2010-01-01

    Full Text Available Monoclonal antibodies have been the most successful therapeutics ever brought to cancer treatment by immune technologies. The use of monoclonal antibodies in B-cell Non-Hodgkin's lymphomas (NHL represents the greatest example of these advances, as the introduction of the anti-CD20 antibody rituximab has had a dramatic impact on how we treat this group of diseases today. Despite this success, several questions about how to optimize the use of monoclonal antibodies in NHL remain open. The best administration schedules, as well as the optimal duration of rituximab treatment, have yet to be determined. A deeper knowledge of the mechanisms underlying resistance to rituximab is also necessary in order to improve the activity of this and of similar therapeutics. Finally, new antibodies and biological agents are entering the scene and their advantages over rituximab will have to be assessed. We will discuss these issues and present an overview of the most significant clinical studies with monoclonal antibodies for NHL treatment carried out to date.

  9. Self-Assembly of Protein Monolayers Engineered for Improved Monoclonal Immunoglobulin G Binding

    Directory of Open Access Journals (Sweden)

    Jeremy H. Lakey

    2011-08-01

    Full Text Available Bacterial outer membrane proteins, along with a filling lipid molecule can be modified to form stable self-assembled monolayers on gold. The transmembrane domain of Escherichia coli outer membrane protein A has been engineered to create a scaffold protein to which functional motifs can be fused. In earlier work we described the assembly and structure of an antibody-binding array where the Z domain of Staphylococcus aureus protein A was fused to the scaffold protein. Whilst the binding of rabbit polyclonal immunoglobulin G (IgG to the array is very strong, mouse monoclonal IgG dissociates from the array easily. This is a problem since many immunodiagnostic tests rely upon the use of mouse monoclonal antibodies. Here we describe a strategy to develop an antibody-binding array that will bind mouse monoclonal IgG with lowered dissociation from the array. A novel protein consisting of the scaffold protein fused to two pairs of Z domains separated by a long flexible linker was manufactured. Using surface plasmon resonance the self-assembly of the new protein on gold and the improved binding of mouse monoclonal IgG were demonstrated.

  10. Molecular mechanism for the action of the anti-CD44 monoclonal antibody MEM-85

    Czech Academy of Sciences Publication Activity Database

    Škerlová, Jana; Král, Vlastimil; Kachala, M.; Fábry, Milan; Bumba, Ladislav; Svergun, D.I.; Tosner, Z.; Veverka, V.; Řezáčová, Pavlína

    2015-01-01

    Roč. 191, č. 2 (2015), s. 214-223 ISSN 1047-8477 R&D Projects: GA ČR(CZ) GA15-11851S EU Projects: European Commission 264257 Institutional support: RVO:68378050 ; RVO:61388971 Keywords : CD44 * Epitope mapping * Monoclonal antibody * MEM-85 * SAXS * NMR Subject RIV: EB - Genetics ; Molecular Biology Impact factor: 2.570, year: 2015

  11. Molecular mechanism for the action of the anti-CD44 monoclonal antibody MEM-85

    Czech Academy of Sciences Publication Activity Database

    Škerlová, Jana; Král, V.; Kachala, M.; Fábry, M.; Bumba, L.; Svergun, D. I.; Tošner, Z.; Veverka, Václav; Řezáčová, Pavlína

    2015-01-01

    Roč. 191, č. 2 (2015), s. 214-223 ISSN 1047-8477 R&D Projects: GA MŠk(CZ) LK11205; GA MŠk(CZ) LO1304 Institutional support: RVO:61388963 Keywords : CD44 * epitope mapping * monoclonal antibody * MEM-85 * NMR * SAXS Subject RIV: CE - Biochemistry Impact factor: 2.570, year: 2015

  12. Rituximab chimeric anti-CD20 monoclonal antibody treatment for adult refractory idiopathic thrombocytopenic purpura

    DEFF Research Database (Denmark)

    Braendstrup, Peter; Bjerrum, Ole W; Nielsen, Ove J

    2005-01-01

    . Recent studies have shown that rituximab, a chimeric anti-CD20 monoclonal antibody, is useful in the treatment of these patients, with overall response rates of about 50%. Most published reports have included a small number patients including case reports. The present study reports the results...

  13. Intravenous cidofovir for resistant cutaneous warts in a patient with psoriasis treated with monoclonal antibodies.

    LENUS (Irish Health Repository)

    McAleer, M A

    2012-02-01

    Human papilloma virus is a common and often distressing cutaneous disease. It can be therapeutically challenging, especially in immunocompromised patients. We report a case of recalcitrant cutaneous warts that resolved with intravenous cidofovir treatment. The patient was immunocompromised secondary to monoclonal antibody therapy for psoriasis.

  14. Monoclonal antibody FsC-47 against carp sperm creatine kinase

    Czech Academy of Sciences Publication Activity Database

    Koubek, Pavel; Elzeinová, Fatima; Šulc, Miroslav; Linhart, O.; Pěknicová, Jana

    2006-01-01

    Roč. 25, č. 3 (2006), s. 154-157 ISSN 1554-0014 R&D Projects: GA ČR(CZ) GA524/03/0178 Institutional research plan: CEZ:AV0Z50520514; CEZ:AV0Z50200510 Keywords : creatin kinase * monoclonal antibody * carp sperm Subject RIV: EB - Genetics ; Molecular Biology Impact factor: 0.411, year: 2006

  15. Anti-interleukin-17 monoclonal antibody ixekizumab in chronic plaque psoriasis

    DEFF Research Database (Denmark)

    Leonardi, Craig; Matheson, Robert; Zachariae, Claus

    2012-01-01

    Type 17 helper T cells have been suggested to play a pathological role in psoriasis. They secrete several proinflammatory cytokines, including interleukin-17A (also known as interleukin-17). We evaluated the safety and efficacy of ixekizumab (LY2439821), a humanized anti-interleukin-17 monoclonal...... antibody, for psoriasis treatment....

  16. A recombinant, fully human monoclonal antibody with antitumor activity constructed from phage-displayed antibody fragments

    NARCIS (Netherlands)

    Huls, GA; Heijnen, IAFM; Cuomo, ME; Koningsberger, JC; Boel, E; de Vries, ARV; Loyson, SAJ; Helfrich, W; Henegouwen, GPV; van Meijer, M; de Kruif, J; Logtenberg, T

    A single-chain Fv antibody fragment specific for the tumor-associated Ep-CAM molecule was isolated from a semisynthetic phage display library and converted into an intact, fully human IgG1 monoclonal antibody (huMab), The purified huMab had an affinity of 5 nM and effectively mediated tumor cell

  17. A novel anti-GPC3 monoclonal antibody (YP7) | Center for Cancer Research

    Science.gov (United States)

    Glypican-3 (GPC3) is an emerging therapeutic target in hepatoma. A novel anti-GPC3 monoclonal antibody (YP7) has been generated through a combination of peptide immunization and high-throughput flow cytometry screening. YP7 binds cell-surface-associated GPC3 with high affinity and exhibits significant hepatoma xenograft growth inhibition in nude mice. The new antibody may have

  18. Perfusion of tumor-bearing kidneys as a model for scintigraphic screening of monoclonal antibodies

    International Nuclear Information System (INIS)

    van Dijk, J.; Oosterwijk, E.; van Kroonenburgh, M.J.; Jonas, U.; Fleuren, G.J.; Pauwels, E.K.; Warnaar, S.O.

    1988-01-01

    Tumor-bearing human kidneys were used in an ex vivo perfusion model to screen monoclonal antibodies, recognizing renal cell carcinoma-associated antigens for diagnostic potential in vivo. Perfusion of tumor-bearing kidneys with /sup 99m/Tc-labeled G250 and RC38 antibody resulted in visualization of the tumor, whereas perfusion with two other monoclonal antibodies, RC2 and RC4, did not lead to tumor visualization. Uptake of radiolabel in normal kidney tissue was low for G250 and RC38 antibody. Tumor-to-kidney tissue ratios after perfusion with G250 and RC38 antibody were 2.7 and 2.2, respectively. After rinsing for 3 hr with unlabeled perfusion fluid the tumor-to-kidney tissue ratios increased to 8.6 for G250 antibody and to 2.7 for RC38 antibody. We conclude that perfusion of tumor-bearing human kidneys with radiolabeled monoclonal antibodies is a relatively simple way to evaluate renal cell carcinoma associated monoclonal antibodies as diagnostic agents in vivo

  19. Preparation of {sup 125}I-labeled monoclonal antibody of bladder neoplasm using lactoperoxidase

    Energy Technology Data Exchange (ETDEWEB)

    Huaifen, Li; Huisheng, Niu; Mingyue, Yuan; Yongzhi, Huang [Chinese Acaolemy of Medical Sciences, Tianjin (China). Inst. of Radiation Medicine

    1994-11-01

    {sup 125}I-labelled monoclonal antibody of bladder neoplasm ({sup 125}I-L{sub 4}B{sub 4}) is prepared using lactoperoxidase. The in-vivo radioactive distribution of {sup 125}I-L{sub 4}B{sub 4} in bare mice shows that {sup 125}I-L{sub 4}B{sub 4} concentrates in the tumour.

  20. Preparation of 125I-labeled monoclonal antibody of bladder neoplasm using lactoperoxidase

    International Nuclear Information System (INIS)

    Li Huaifen; Niu Huisheng; Yuan Mingyue; Huang Yongzhi

    1994-01-01

    125 I-labelled monoclonal antibody of bladder neoplasm ( 125 I-L 4 B 4 ) is prepared using lactoperoxidase. The in-vivo radioactive distribution of 125 I-L 4 B 4 in bare mice shows that 125 I-L 4 B 4 concentrates in the tumour