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  1. 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

  2. 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.

  3. 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

  4. 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?

  5. 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

  6. 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)

  7. 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.

  8. 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

  9. 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

  10. 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

  11. 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).

  12. 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.

  13. 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

  14. 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

  15. 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.''

  16. Lymphoma, melanoma, colon cancer: diagnosis and treatment with radiolabeled monoclonal antibodies. The 1986 Eugene P. Pendergrass New Horizons Lecture

    International Nuclear Information System (INIS)

    Larson, S.M.

    1987-01-01

    The development of monoclonal antibodies for use as in vivo carriers of radioactivity for diagnosis and therapy of malignant neoplasms is proceeding rapidly within academic and commercial sectors. The author and his colleagues studied anticancer antibodies formed against tumors of both somatic and hematopoietic origins. Several general principles have been established with the work with somatic tumors, including the following: Improved tumor-to-normal-tissue ratios can be achieved with Fab fragments as opposed to whole IgG; each antitumor antibody has a characteristic biodistribution in humans that cannot be readily predicted from tissue or small animal studies; and for many antibodies, there is a strong dependency of tumor uptake on total mass amount of antibody administered (greater uptake with greater mass dose). Initial work with iodine-131 labeled Fab fragments of the antimelanoma antibodies, 96.5 and 48-7, documented that tumor uptake was broadly proportional to antigen content of the tumors and that under optimal conditions, some tumors were sufficiently loaded with radiolabeled antibody to serve as radiation therapy. The antitumor antibody B-72.3, as IgG, has been particularly promising when administered intraperitoneally. In ten patients who were administered I-131 B-72.3 via a Tenkhoff catheter, the sensitivity and specificity of tumor location were excellent for peritoneal implants, and in three of these patients, surgically confirmed tumor was seen with the radiolabeled antibody technique when abdominal computed tomography and magnetic resonance studies were negative

  17. 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)

  18. 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)

  19. Search for new and improved radiolabeling methods for monoclonal antibodies

    International Nuclear Information System (INIS)

    Hiltunen, J.V.

    1993-01-01

    In this review the selection of different radioisotopes is discussed as well as the various traditional or newer methods to introduce the radiolabel into the antibody structure. Labeling methods for radiohalogens, for technetium and rhenium isotopes, and for 3-valent cation radiometals are reviewed. Some of the newer methods offer simplified labeling procedures, but usually the new methods are more complicated than the earlier ones. However, new labeling methods are available for almost any radioelement group and they may result in better preserved original natural of the antibody and lead to better clinical results. (orig./MG)

  20. Molecular imaging of rheumatoid arthritis by radiolabelled monoclonal antibodies: new imaging strategies to guide molecular therapies

    Energy Technology Data Exchange (ETDEWEB)

    Malviya, G.; Dierckx, R.A. [Department of Nuclear Medicine and Molecular Imaging, University Medical Centre Groningen, University of Groningen (Netherlands); Conti, F. [Rheumatology Unit, I Faculty of Medicine and Surgery, Sapienza University of Rome (Italy); Chianelli, M. [Department of Nuclear Medicine and Molecular Imaging, University Medical Centre Groningen, University of Groningen (Netherlands); Unit of Nuclear Medicine, Regina apostolorum Hospital, Albano, Rome (Italy); Scopinaro, F. [Nuclear Medicine Department, Sapienza University of Rome, St. Andrea Hospital, Rome (Italy); Signore, A. [Department of Nuclear Medicine and Molecular Imaging, University Medical Centre Groningen, University of Groningen (Netherlands); Nuclear Medicine Department, Sapienza University of Rome, St. Andrea Hospital, Rome (Italy)

    2010-02-15

    The closing of the last century opened a wide variety of approaches for inflammation imaging and treatment of patients with rheumatoid arthritis (RA). The introduction of biological therapies for the management of RA started a revolution in the therapeutic armamentarium with the development of several novel monoclonal antibodies (mAbs), which can be murine, chimeric, humanised and fully human antibodies. Monoclonal antibodies specifically bind to their target, which could be adhesion molecules, activation markers, antigens or receptors, to interfere with specific inflammation pathways at the molecular level, leading to immune-modulation of the underlying pathogenic process. These new generation of mAbs can also be radiolabelled by using direct or indirect method, with a variety of nuclides, depending upon the specific diagnostic application. For studying rheumatoid arthritis patients, several monoclonal antibodies and their fragments, including anti-TNF-{alpha}, anti-CD20, anti-CD3, anti-CD4 and anti-E-selectin antibody, have been radiolabelled mainly with {sup 99m}Tc or {sup 111}In. Scintigraphy with these radiolabelled antibodies may offer an exciting possibility for the study of RA patients and holds two types of information: (1) it allows better staging of the disease and diagnosis of the state of activity by early detection of inflamed joints that might be difficult to assess; (2) it might provide a possibility to perform 'evidence-based biological therapy' of arthritis with a view to assessing whether an antibody will localise in an inflamed joint before using the same unlabelled antibody therapeutically. This might prove particularly important for the selection of patients to be treated since biological therapies can be associated with severe side-effects and are considerably expensive. This article reviews the use of radiolabelled mAbs in the study of RA with particular emphasis on the use of different radiolabelled monoclonal antibodies for

  1. Molecular imaging of rheumatoid arthritis by radiolabelled monoclonal antibodies: new imaging strategies to guide molecular therapies

    International Nuclear Information System (INIS)

    Malviya, G.; Dierckx, R.A.; Conti, F.; Chianelli, M.; Scopinaro, F.; Signore, A.

    2010-01-01

    The closing of the last century opened a wide variety of approaches for inflammation imaging and treatment of patients with rheumatoid arthritis (RA). The introduction of biological therapies for the management of RA started a revolution in the therapeutic armamentarium with the development of several novel monoclonal antibodies (mAbs), which can be murine, chimeric, humanised and fully human antibodies. Monoclonal antibodies specifically bind to their target, which could be adhesion molecules, activation markers, antigens or receptors, to interfere with specific inflammation pathways at the molecular level, leading to immune-modulation of the underlying pathogenic process. These new generation of mAbs can also be radiolabelled by using direct or indirect method, with a variety of nuclides, depending upon the specific diagnostic application. For studying rheumatoid arthritis patients, several monoclonal antibodies and their fragments, including anti-TNF-α, anti-CD20, anti-CD3, anti-CD4 and anti-E-selectin antibody, have been radiolabelled mainly with 99m Tc or 111 In. Scintigraphy with these radiolabelled antibodies may offer an exciting possibility for the study of RA patients and holds two types of information: (1) it allows better staging of the disease and diagnosis of the state of activity by early detection of inflamed joints that might be difficult to assess; (2) it might provide a possibility to perform 'evidence-based biological therapy' of arthritis with a view to assessing whether an antibody will localise in an inflamed joint before using the same unlabelled antibody therapeutically. This might prove particularly important for the selection of patients to be treated since biological therapies can be associated with severe side-effects and are considerably expensive. This article reviews the use of radiolabelled mAbs in the study of RA with particular emphasis on the use of different radiolabelled monoclonal antibodies for therapy decision-making and

  2. 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

  3. 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.

  4. 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.

  5. 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.)

  6. Tumor-specific binding of radiolabeled G-22 monoclonal antibody in glioma patients

    Energy Technology Data Exchange (ETDEWEB)

    Yoshida, Jun; Wakabayashi, Toshihiko; Mizuno, Masaaki; Sugita, Kenichiro; Oshima, Motoo; Tadokoro, Masanori; Sakuma, Sadayuki [Nagoya Univ. (Japan). Faculty of Medicine; Seo, Hisao

    1992-03-01

    Iodine-131-labeled G-22 monoclonal antibody F(ab'){sub 2} fragment reacting specifically with a glioma-associated surface glycoprotein was administered to 12 glioma patients to investigate its use in radioimaging of intracranial gliomas. No immediate or delayed side effects were attributable to antibody injection. Nine patients received the radiolabeled complex intravenously. The images of low-grade gliomas were generally poor and disappeared within 4 days. High-contrast images were obtained beyond the 7th day in high-grade gliomas except one case in the pineal region. Three patients received intraventricular or intratumoral administration. Clear images of all tumors were demonstrated from the 2nd until later than the 7th day. One patient with cerebrospinal fluid (CSF) dissemination of brainstem glioma demonstrated negative CSF cytology after intraventricular administration. (author).

  7. CT-SPECT fusion to correlate radiolabeled monoclonal antibody uptake with abdominal CT findings

    International Nuclear Information System (INIS)

    Kramer, E.L.; Noz, M.E.; Sanger, J.J.; Megibow, A.J.; Maguire, G.Q.

    1989-01-01

    To enhance the information provided by computed tomography (CT) and single photon emission computed tomography (SPECT) performed with radiolabeled, anti-carcinoembryonic antigen monoclonal antibody (MoAb), the authors performed fusion of these types of images from eight subjects with suspected colorectal adenocarcinoma. Section thickness and pixel size of the two studies were matched, coordinates of corresponding points from each study were identified, and CT sections were translated, rotated, and reprojected to match the corresponding SPECT scans. The CT-SPECT fusion enabled identification of anatomic sites of tumor-specific MoAb accumulation in four cases, showed non-specific MoAb accumulation in two, and helped confirm information only suggested by the two studies separately in one

  8. 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

  9. Effects of radiolabelled monoclonal antibody infusion on blood leukocytes in cancer patients

    International Nuclear Information System (INIS)

    Gridley, D.S.; Slater, J.M.; Stickney, D.R.

    1990-01-01

    This study was undertaken to investigate the effects of a single infusion of radiolabelled murine monoclonal antibody (MAb) on peripheral blood leukocytes in cancer patients. Eleven patients with disseminated colon cancer, malignant melanoma, or lung adenocarcinoma were infused with 111In-labelled anti-ZCE 025, anti-p97 type 96.5c, or LA 20207 MAb, respectively. Blood samples were obtained before infusion, immediately after infusion (1 hr), and at 4 and 7 days postinfusion. Flow cytometry analysis of CD3+, CD4+, CD8+, CD16+, and CD19+ lymphocytes showed increasing CD4:CD8 ratios in seven patients after infusion. This phenomenon was not restricted to antibody subclass or to type of cancer. Two of the remaining patients exhibited a marked post-infusion increase in CD8+ cells. In all three patients with malignant melanoma, decreasing levels of CD16+ lymphocytes were noted after infusion and natural killer cell cytotoxicity showed fluctuations which paralleled the changes in the CD16+ subpopulation. Oxygen radical production by phagocytic cells was markedly affected in three subjects. These results suggest that a single infusion of radiolabelled murine MAb may alter the balance of critical lymphocyte subpopulations and modulate other leukocyte responses in cancer patients

  10. Mesenteric vascular occlusion: a new diagnostic method using a radiolabeled monoclonal antibody reactive with platelets

    International Nuclear Information System (INIS)

    Oster, Z.H.; Som, P.; Zamora, P.O.

    1989-01-01

    A new method for diagnosing mesenteric vaso-occlusive bowel disease with the use of radioimmunoscintigraphy was developed and tested in experimental models of arterial and venous disease, as well as in a model simulating bowel strangulation. The method involves the use of a monoclonal antibody fragment mixture that binds to platelets. The antibody was labeled with technetium-99m, and imaging was performed with a gamma camera in the planar and single photon emission computed tomography modes. This method allowed visualization of areas of ischemia of 1-6 hours duration in bowel loops in 19 dogs 90-180 minutes after injection of the radiolabeled antibody. No bowel radioactivity accumulation occurred in dogs that underwent the same surgical procedure but were given a nonspecific Tc-99m-labeled antibody or in normal dogs given the specific antibody. It appears that the radiolabeled antibody used, which has higher reactivity with human platelets than with dog platelets, will be a good agent for noninvasive diagnosis of mesenteric vaso-occlusive disease in humans. It may also play a role in the intraoperative determination of the extent and location of ischemic bowel segments

  11. 166Ho and 90Y labeled 6D2 monoclonal antibody for targeted radiotherapy of melanoma: Comparison with 188Re radiolabel

    International Nuclear Information System (INIS)

    Thompson, S.; Ballard, B.; Jiang, Z.; Revskaya, E.; Sisay, N.; Miller, W.H.; Cutler, C.S.; Dadachova, E.; Francesconi, L.C.

    2014-01-01

    Introduction: An approach to radioimmunotherapy (RIT) of metastatic melanoma is the targeting of melanin pigment with monoclonal antibodies (mAbs) to melanin radiolabeled with therapeutic radionuclides. The proof of principle experiments were performed using a melanin-binding antibody 6D2 of IgM isotype radiolabeled with a β emitter 188 Re and demonstrated the inhibition of tumor growth. In this study we investigated the efficacy of 6D2 antibody radiolabeled with two other longer lived β emitters 90 Y and 166 Ho in treatment of experimental melanoma, with the objective to find a possible correlation between the efficacy and half-life of the radioisotopes which possess high energy β (E max > 1.5 MeV) emission properties. Methods: 6D2 was radiolabeled with longer lived β emitters 90 Y and 166 Ho in treatment of experimental melanoma in A2058 melanoma tumor-bearing nude mice. The immunoreactivity of the radiolabeled 6D2 mAb, its in vitro binding to the MNT1 human melanoma cells, the biodistribution and therapy in A2058 human melanoma bearing nude mice as well as dosimetry calculations were performed. Results: When labeled with the longer lived 90 Y radionuclide, the 6D2 mAb did not produce any therapeutic effect in tumor bearing mice while the reduction of the tumor growth by 166 Ho-6D2 was very similar to the previously reported therapy results for 188 Re-6D2. In addition, 166 Ho-labeled mAb produced the therapeutic effect on the tumor without any toxic effects while the administration of the 90 Y-labeled radioconjugate was toxic to mice with no appreciable anti-tumor effect. Conclusions: 166 Ho-labeled mAb to melanin produced some therapeutic effect on the tumor without any toxic effects while the administration of the 90 Y-labeled radioconjugate was toxic to mice with no appreciable anti-tumor effect. We concluded that the serum half-life of the 6D2 carrier antibody matched well the physical half-life of 166 Ho to deliver the tumoricidal absorbed dose to the

  12. Study of conjugation and radiolabeling of monoclonal antibody rituximab for use in radionuclide therapy

    International Nuclear Information System (INIS)

    Massicano, Adriana Vidal Fernandes

    2011-01-01

    Lymphomas are tumors originated from the transformation of a lymphocyte in the lymphatic system. The most common lymphoma is the Non-Hodgkin Lymphoma (NHL). Advances in immunology and molecular biology have been improving NHL's detection and treatment strategies development, such as Radioimmunotherapy (RIT). Rituximab is an anti-CD20 monoclonal antibody used as immunotherapeutic to treat refractory or relapsed NHL. The goal of the present work was to conjugate this antibody to DOTA-NHS-ester bifunctional chelator and to radiolabel it with 177 Lu radioisotope in order to develop a radio immunotherapeutic agent for NHL's treatment. Different rituximab to DOTA molar ratios (1:5, 1:10, 1:20, 1:50, 1:250, 1:500 and 1:1000) were evaluated in order to determine the best condition for obtaining the highest radiochemical purity of radio immunotherapeutic. The stability of the unlabeled immuno conjugated was evaluated by high performance liquid chromatography (HPLC) for up to 240 days in different storage conditions. The stability of the labeled preparations was evaluated either after storing at 2-8 degree C or incubation in human serum at 37 degree C. The binding to serum proteins was also determined. In vivo studies were performed in healthy Swiss mice, in order to characterize the biological properties of labeled conjugate. Finally, preliminary studies of radio immuno conjugated competitive binding to CD20 positive Raji cells were carried out in order to analyze if the process of conjugation and radiolabeling compromises the immunoreactivity of the antibody. The conjugation applying lower antibody to chelator molar ratios (1:5, 1:10 and 1:20) showed high stability when stored for up to 240 days in different conditions. The HPLC analysis showed that the monoclonal antibody conjugated in molar ratio 1:50 was labeled with higher radiochemical purity (> 95%) when purified in PD-10 column. This conjugate showed reasonable stability at 2-8 degree C. The analysis of the

  13. Distribution and pharmacokinetics of radiolabeled monoclonal antibody OC 125 after intravenous and intraperitoneal administration in gynecologic tumors

    International Nuclear Information System (INIS)

    Haisma, H.J.; Moseley, K.R.; Battaile, A.; Griffiths, T.C.; Knapp, R.C.

    1988-01-01

    Radiolabeled monoclonal antibodies may be useful for radioimmunotherapy of gynecologic tumors. Iodine 131-labeled F(ab')2 fragments of a monoclonal antibody, OC 125, with specificity for ovarian carcinoma, were used to study the distribution and pharmacokinetics of this antibody in patients with gynecologic tumors. The radiolabeled antibody was injected intravenously or intraperitoneally into 10 patients suspected of having ovarian cancer. Blood and urine samples were used for pharmacokinetic studies, and biopsy specimens were examined for the uptake of antibody. The serum half-life of the labeled antibody was 30 hours after intravenous administration, with 20% of the injected dose per liter detected at 24 hours. After intraperitoneal injection, the appearance of antibody in serum was slow, with a maximum level of 1.4% of the injected dose per liter at 24 hours. Urinary excretion of the radiolabeled antibody was similar for intravenous and intraperitoneal administration, with approximately 50% of the injected dose excreted after 48 hours. Intraperitoneal administration of the radiolabeled antibody resulted in a higher uptake of antibody in the tumor and a lower uptake of antibody in normal tissues. On the basis of this limited study, intraperitoneal administration of radiolabeled antibody is preferred over intravenous administration for radioimmunotherapy of ovarian cancer

  14. Tc-99m direct radiolabeling of monoclonal antibody ior egf/r3: quality control and image studies in mice

    International Nuclear Information System (INIS)

    Dias, Carla Roberta; Marczewski, Barbara; Moraes, Vanessa; Barboza, Marycel Figols de; Osso Junior, Joao Alberto

    2005-01-01

    Monoclonal antibodies (Mabs) have been useful for immunoscintigraphic applications in clinical diagnosis since they were introduced in the practice of nuclear medicine. The ior egf/r3 (Centis, Cuba) is a murine monoclonal antibody against epidermal growth factor receptor (EGF-R) and has been widely used in the radioimmunodiagnosis of tumors of epithelial origin. Labeled with 99m Tc, its main application in Nuclear Medicine is the follow up, detection and evaluation of tumor recurrences. The objective of this work is to describe the preparation of a lyophilized formulation (kit) for radiolabeling the Mab ior egf/r3 with 99m Tc for immunoscintigraphic applications. Radiolabeling efficiency, effects on immunoreactivity, image studies and stability of the formulation are reported. The study demonstrated that the kit formulation can be labeled with 99m Tc at high yields and can be used to visualize in vivo human tumors of epithelial origin by immunoscintigraphy studies.(author)

  15. Preparation of monoclonal antibodies against cardiac myosin and some radiolabelling studies

    International Nuclear Information System (INIS)

    Bapat, K.; Venkatesh, M.; Pillai, M.R.A.; Sarma, H.D.; Sainis, K.B.

    1998-01-01

    Monoclonal antibodies were raised against myosin, a specific indicator of myocardial infarction and labelled with 125 I and 99m Tc. Human cardiac myosin was isolated from normal human heart and was used for raising the monoclonal antibodies by the hybridoma technique. Antibody producing clones were identified by ELISA and cloning was done by the limiting dilution technique. Of the 13 clones obtained, 4 were deemed suitable for further studies. The antibodies were grown in ascites, purified, isotyped and their cross reactions with other forms of myosin were estimated. All the clones showed negligible cross reaction with rabbit myosin, but reacted to different extents with bovine skeletal myosin. The most avid antibody Mab-4G4 was chosen for further labelling studies. Mab-4G4 was labelled with 125 I using different oxidising agents such as iodogen, chloramine-T and lactoperoxidase. Purified radioiodinated antibody with radiochemical purity >95% could be obtained by gel filtration. Immunoreactivity was retained as tested by binding to myosin immobilised on a solid support. Mab-4G4 was also labelled with 99m Tc using stannous tartrate as the reducing agent. Radiolabelling yield was ∼60%, the purity was >95% and the immunoreactivity was retained. Both the labelled preparations were tested for bio-distribution in normal and infarcted rats. The activity accumulation in the infarcted region was ∼ 1.5 and 3.5 times as that in normal heart muscle for 125 I and 99m Tc labelled Mab-4G4 respectively. The major problem with the iodinated antibody was the in vivo deiodination resulting in very high percentage of activity in the thyroid. Although the fraction of the total activity associated with the infarcted heart is not very impressive, the fact that the activities with the infarcted and normal hearths are significantly different is heartening. With further optimisation of labelling and use of F(ab)'2 fragments, better delineation of the infarct sites is aspired. (author)

  16. 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.)

  17. Systemic perfusion: a method of enhancing relative tumor uptake of radiolabeled monoclonal antibodies

    Energy Technology Data Exchange (ETDEWEB)

    Wahl, R.L.; Piko, C.R.; Beers, B.A.; Geatti, O.; Johnson, J.; Sherman, P. (Michigan Univ., Ann Arbor, MI (USA). Dept. of Internal Medicine)

    1989-01-01

    The authors evaluated the feasibility of systemic vascular perfusion with saline (mimicking plasmapheresis) as a method to enhance tumor-specific monoclonal antibody (MoAb) tumor/background ratios. Perfusion in rats dropped whole-body 5G6.4 levels significantly at both perfusion times. The drop in whole-body radioactivity with perfusion was significantly greater for the animals perfused at 4 h post i.v. 5G6.4 antibody injection (48.3 +- 5.1%) than for those perfused at 24h post i.v. antibody injection (32.9 +- 2.9%). In the nude mice with ovarian cancer xenografts, gamma camera images of tumors were visually and quantitatively by computer image analysis enhanced by perfusion, with a 2.33-fold greater decline in whole body uptake than in the tumor. These studies show that much background antibody radioactivity can be removed using whole-body perfusion with saline, that the decline in whole body activity is larger with 4 than 24h perfusion and that tumor imaging can be enhanced by this approach. This and similar approaches that increase relative tumor antibody uptake such as plasmapheresis may be useful in imaging and therapy with radiolabeled antibodies.

  18. Pharmacokinetic study of radiolabeled anti-colorectal carcinoma monoclonal antibodies in tumor-bearing nude mice

    Energy Technology Data Exchange (ETDEWEB)

    Douillard, J.Y.; Chatal, J.F.; Curtet, C.; Kremer, M.; Saccavini, J.C.; Peuvrel, P.; Koprowski, H.

    1985-09-01

    Monoclonal antibodies (MoAbs) 17-1A and 19-9, which specifically bind human colorectal carcinoma (CRC) cells, were tested for their usefulness in localizing colorectal tumors in nude mice. One of the /sup 131/I-labeled MoAbs and an irrelevant /sup 125/I-labeled immunoglobulin of the same isotype were injected into nude mice simultaneously bearing a human CRC and a human melanoma. The percentage of the injected dose of antibody per gram of tissue, the CRC/tissue ratios of antibody distribution, and the localization indicees were calculated at various time intervals (2 h to 10 days). For both MoAbs, labeling to a specific activity of 10 ..mu..Ci/..mu..g by the iodogen method gave optimum immunoreactivity. The accumulation of MoAb 17-1A in CRC reached its maximum at 5 days and remained at this level for up to 9 days postinjection. For MoAb 19-9, which detects a circulating antigen shed by the tumor into the serum, the accumulation in the CRC was maximum at 24 h, and decreased thereafter. The CRC/organ ratios and localization indices for-both MoAbs increased with time in the CRC tissue, but remained low and unchanged in the melanoma and normal tissue. Using F(ab')/sub 2/ antibody fragments, faster kinetics with earlier maximum accumulation, higher tumor/organ ratios, and better localization indices were achieved than with intact MoAbs. The data obtained was useful in defining parameters which must be considered before radiolabeled MoAbs are used in cancer patients for diagnostic purposes.

  19. Radiolabeled monoclonal antibodies. Development of a new method to remove circulating activity - diagnostic applications and implications for therapy

    International Nuclear Information System (INIS)

    Norrgren, K.

    1993-04-01

    The aim of this thesis was to develop and investigate the usefulness of extracorporeal immunoadsorption (ECIA) to remove circulating activity after the localization of radiolabeled monoclonal antibodies to tumors. A compartment model, based on the biokinetics of 125 I-labeled antibodies 96.5 was developed to estimate the effect of ECIA on the tumor-to-normal tissue ratios. ECIA was simulated at different times after injection of the antibodies and the calculations showed an increased diagnostic ratio for several hours after the ECIA procedure, and that an enhancement of the therapeutic ratio was possible. These results led to the development of animal models where the ECIA could be evaluated and the biokinetic behaviour of different radiolabeled monoclonal antibodies investigated with and without the application of ECIA. A general ECIA method, based on biotinylated antibodies and an avidin agarose column as adsorbent, was developed. Studies in tumor bearing nude rats showed that ECIA enhanced of the tumor-to-normal tissue activity ratios by a factor of 4 for the liver, kidneys and bone marrow. For the L6 antibody, the image contrast of tumors localized in one kidney of the rats, was increased from 1.1 to 1.6. A software anthropomorphic phantom was used in Monte Carlo simulations of clinically realistic scintillation camera image acquisition. The effect of ECIA on the contrast enhancement and on the detectability of simulated tumors located centrally in the liver was studied. The contrast increased linearly with an increasing tumor/liver ratio. The contrast was higher for SPECT than for planar images and a contrast of 1.15 required a tumor/liver activity ratio of 1.9 for SPECT and 4.5 for planar images. ECIA in combination with SPECT imaging of radiolabeled antibodies has a great potential in increasing the detectability of tumors. These studies have shown the possibility with ECIA to increase the contrast in radioimmunoimaging and to enhance the therapeutic ratio

  20. Kinetics and tissue distribution of the radiolabeled chimeric monoclonal antibody MOv18 IgG and F(ab')2 fragments in ovarian carcinoma patients

    NARCIS (Netherlands)

    Buist, M. R.; Kenemans, P.; den Hollander, W.; Vermorken, J. B.; Molthoff, C. J.; Burger, C. W.; Helmerhorst, T. J.; Baak, J. P.; Roos, J. C.

    1993-01-01

    Twenty-four patients suspected of having ovarian carcinoma received i.v. injection with a combination of radiolabeled intact IgG (1 mg) and F(ab')2 fragments (1 mg) of the chimeric monoclonal antibody MOv18, each form labeled with 1.85 MBq 131I or 125I. Laparotomy was performed either 2 or 6 days

  1. 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.)

  2. Radiolabeled Humanized Anti-CD3 Monoclonal Antibody Visilizumab for Imaging Human T-Lymphocytes

    NARCIS (Netherlands)

    Malviya, Gaurav; D'Alessandria, Calogero; Bonanno, Elena; Vexler, Vladimir; Massari, Roberto; Trotta, Carlo; Scopinaro, Francesco; Dierckx, Rudi; Signore, Alberto

    2009-01-01

    Visilizumab is an IgG(2) humanized monoclonal antibody (mAb) characterized by non-Fc gamma R binding and specific to the CD3 antigen, expressed on more than 95% of circulating resting T-lymphocytes and on activated T-lymphocytes homing in inflamed tissues. We hypothesized that the use of a

  3. Antitumor activity of anti-C-ERC/mesothelin monoclonal antibody in vivo.

    Science.gov (United States)

    Inami, Koichi; Abe, Masaaki; Takeda, Kazuyoshi; Hagiwara, Yoshiaki; Maeda, Masahiro; Segawa, Tatsuya; Suyama, Masafumi; Watanabe, Sumio; Hino, Okio

    2010-04-01

    Mesothelioma is an aggressive cancer often caused by chronic asbestos exposure, and its prognosis is very poor despite the therapies currently used. Due to the long latency period between asbestos exposure and tumor development, the worldwide incidence will increase substantially in the next decades. Thus, novel effective therapies are warranted to improve the prognosis. The ERC/mesothelin gene (MSLN) is expressed in wide variety of human cancers, including mesotheliomas, and encodes a precursor protein cleaved by proteases to generate C-ERC/mesothelin and N-ERC/mesothelin. In this study, we investigated the antitumor activity of C-ERC/mesothelin-specific mouse monoclonal antibody, 22A31, against tumors derived from a human mesothelioma cell line, ACC-MESO-4, in a xenograft experimental model using female BALB/c athymic nude mice. Treatment with 22A31 did not inhibit cell proliferation of ACC-MESO-4 in vitro; however, therapeutic treatment with 22A31 drastically inhibited tumor growth in vivo. 22A31 induced antibody-dependent cell-mediated cytotoxicity by natural killer (NK) cells, but not macrophages, in vitro. Consistently, the F(ab')(2) fragment of 22A31 did not inhibit tumor growth in vivo, nor did it induce antibody-dependent cell mediated cytotoxicity (ADCC) in vitro. Moreover, NK cell depletion diminished the antitumor effect of 22A31. Thus, 22A31 induced NK cell-mediated ADCC and exerted antitumor activity in vivo. 22A31 could have potential as a therapeutic tool to treat C-ERC/mesothelin-expressing cancers including mesothelioma.

  4. Radiolabeling and biotinylation of internalizing monoclonal antibody chimeric BR96: Potential use of extracorporeal immunoadsorption with enhanced tumor radioactivity retention of Iodine, Indium and Rhenium

    International Nuclear Information System (INIS)

    Chen, JianQing.

    1997-01-01

    In this thesis, methodology of radiolabeling and simultaneous biotinylation for internalizing monoclonal antibody chimeric BR96 have been investigated by using three element groups of potential therapeutic radionuclides iodine, indium and rhenium, and their different labeling methods. The biodistribution and kinetics of biotinylated and radiolabeled chiBR96 have been studied in colon carcinoma isografted rats. The potential use of ECIA, based on the biotin-avidin concept, has been evaluated and compared with the approach of avidin 'chase' in the same animal tumor model with respect to an enhancement of tumor-to-normal tissue (T/N) activity ratio. 131 refs

  5. Radiolabeling and biotinylation of internalizing monoclonal antibody chimeric BR96: Potential use of extracorporeal immunoadsorption with enhanced tumor radioactivity retention of Iodine, Indium and Rhenium

    Energy Technology Data Exchange (ETDEWEB)

    Chen, JianQing

    1997-01-01

    In this thesis, methodology of radiolabeling and simultaneous biotinylation for internalizing monoclonal antibody chimeric BR96 have been investigated by using three element groups of potential therapeutic radionuclides iodine, indium and rhenium, and their different labeling methods. The biodistribution and kinetics of biotinylated and radiolabeled chiBR96 have been studied in colon carcinoma isografted rats. The potential use of ECIA, based on the biotin-avidin concept, has been evaluated and compared with the approach of avidin `chase` in the same animal tumor model with respect to an enhancement of tumor-to-normal tissue (T/N) activity ratio. 131 refs.

  6. Direct 99mTc labeling of monoclonal antibodies: radiolabeling and in vitro stability

    International Nuclear Information System (INIS)

    Garron, J.Y.; Moinereau, M.; Pasqualini, R.; Saccavini, J.C.

    1991-01-01

    Direct labeling involves 99m Tc binding to different donor groups on the protein, giving multiple binding sites of various affinities resulting in an in vivo instability. The stability has been considerably improved by activating the antibody using a controlled reduction reaction (using 2-aminoethanethiol). This reaction generates sulfhydryl groups, which are known to strongly bind 99m Tc. The direct 99m Tc antibody labeling method was explored using whole antibodies and fragments. Analytical methods were developed for routine evaluation of radiolabeling yield and in vitro stability. Stable direct antibody labeling with 99m Tc requires the generation of sulfhydryl groups, which show high affinity binding sites for 99m Tc. Such groups are obtained with 2-aminoethanethiol (AET), which induces the reduction of the intrachain or interchain disulfide bond, with no structural deterioration or any loss of immunobiological activity of the antibody. The development of fast, reliable analytical methods has made possible the qualitative and quantitative assessment of technetium species generated by the radiolabeling process. Labeling stability is determined by competition of the 99m Tc-antibody bond with three ligands, Chelex 100 (a metal chelate-type resin), free DTPA solution and 1% HSA solution. Very good 99m Tc-antibody stability is obtained with activated IgG (IgGa) and Fab' fragment, which makes these substances possible candidates for immunoscintigraphy use. (author)

  7. Tc-{sup 99m} direct radiolabeling of monoclonal antibody ior egf/r3: quality control and image studies in mice

    Energy Technology Data Exchange (ETDEWEB)

    Dias, Carla Roberta; Marczewski, Barbara; Moraes, Vanessa; Barboza, Marycel Figols de; Osso Junior, Joao Alberto [Instituto de Pesquisas Energeticas e Nucleares (IPEN-CNEN/SP), SP (Brazil). Centro de Radiofarmacia]. E-mail: crdias@ipen.br

    2005-10-15

    Monoclonal antibodies (Mabs) have been useful for immunoscintigraphic applications in clinical diagnosis since they were introduced in the practice of nuclear medicine. The ior egf/r3 (Centis, Cuba) is a murine monoclonal antibody against epidermal growth factor receptor (EGF-R) and has been widely used in the radioimmunodiagnosis of tumors of epithelial origin. Labeled with 99m Tc, its main application in Nuclear Medicine is the follow up, detection and evaluation of tumor recurrences. The objective of this work is to describe the preparation of a lyophilized formulation (kit) for radiolabeling the Mab ior egf/r3 with 99m Tc for immunoscintigraphic applications. Radiolabeling efficiency, effects on immunoreactivity, image studies and stability of the formulation are reported. The study demonstrated that the kit formulation can be labeled with 99m Tc at high yields and can be used to visualize in vivo human tumors of epithelial origin by immunoscintigraphy studies.(author)

  8. /sup 99m/Tc radiolabelling and quality control tests of anti-melanoma monoclonal antibodies and F(ab')/sub 2/ fragments for immunoscintigraphy

    International Nuclear Information System (INIS)

    Callegaro, L.; Deleide, G.; Dovis, M.; Cecconato, E.; Scassellati, G.A.

    1986-01-01

    Tumour radioimmunodetection was first developed by using radiolabelled polyclonal antibodies, raised in goats against tumour associated antigens (TAA). The availability of monoclonal antibodies to TAA has definitely contributed to more extensive in vivo use of radiolabelled antibodies. However, many factors are involved in tumour radioimmunolocalization, related either to the antibody and radioisotope features or to the natural history of the tumour itself. The experimental protocol developed by the authors allows a full evaluation of the properties of a particular MoAb.This paper illustrates the work done with on a particular set of monoclonal antibodies, raised against human melanoma associated antigens, with the aim of visualizing primary and metastatic lesions in melanoma patients

  9. Evaluation of tumor targeting with radiolabeled F(ab2 fragment of a humanized monoclonal antibody

    Directory of Open Access Journals (Sweden)

    "Babaei MH

    2002-08-01

    Full Text Available Humanized monoclonal antibody U36 and its F(ab'2 fragment, radio labeled with 125I, were tested for tumor localization in nude mice bearing a squamous cell carcinoma xenograft line derived from a head and neck carcinoma. Monoclonal antibody IgG or F(ab'2 fragment were injected in parallel and at days 1, 2 and 3, mice were dissected for determination of isotope biodistribution. IgG as well as F(ab'2 showed highly specific localization in tumor tissue. The mean tumor uptake (n=3 is expressed as the percentage of the injected dose per gram of tumor tissue (%ID/g. %ID/g of IgG was 11.7% at day 1 and decreased to 10.9% at day 3 whereas %ID/g of F(ab'2 was 2.9% at day 1 and decreased on following days. Tumor to blood ratios (T/B at day 1 were 0.86 for IgG and 1.32 for F(ab'2 and reached a maximum at day 3 with values of 4.41 and 1.84 respectively. These findings suggest that the superior tumor to non-tumor ratios in the day of 1 render the F(ab'2 fragment more qualified for specific targeting radioisotopes to tumor xenografts in this exprimental setting.

  10. Monoclonal antibody-dendrimer conjugates enable radiolabeling of antibody with markedly high specific activity with minimal loss of immunoreactivity

    Energy Technology Data Exchange (ETDEWEB)

    Kobayashi, H.; Togashi, K. [Kyoto Univ. (Japan). School of Medicine; Sato, N.; Saga, T.; Nakamoto, Y.; Ishimori, T.; Konishi, J. [Dept. of Nuclear Medicine and Medical Imaging, Kyoto Univ. Graduate School of Medicine, Kyoto (Japan); Toyama, S. [Inst. for Virus Research, Kyoto Univ., Kyoto (Japan); Brechbiel, M.W. [Chemistry Section, Radiation Oncology Branch, National Cancer Inst., National Inst. of Health, Bethesda, Md. (United States)

    2000-09-01

    For the purpose of radioimmunotherapy, labelling of monoclonal antibody with high specific activity is often necessary, especially when using a radionuclide with a shorter half-life. Polyamine dendrimers (PAMAM) are novel synthetic polymeric molecules with large numbers of amine residues on their spherical surface. In order to bind large numbers of radiometals to single antibody molecules, the generation-4 PAMAM (G4), which has 64 amines, was conjugated with 43 molecules of 2-(p-isothiocyanatobenzyl)-6-methyl-diethylene triamine penta-acetic acid (1B4M), a derivative of DTPA. This product [G4-(1B4M){sub 43}] was then conjugated with OST7, a murine monoclonal IgG{sub 1}. We evaluated the achievable specific activity for {sup 111}In labeling, immunore-activity, biodistribution, and tumor targeting in mice of the {sup 111}In- or {sup 153}Gd-OST7-G4-(1B4M){sub 43} as compared with radiolabeled OST7-1B4M or 56C-1B4M. The maximum specific activity of {sup 111}In-OST7-G4-(1B4M){sub 43} and {sup 111}In-OST7-1B4M was 470 and 8.7 GBq/mg (12,700 and 263 mCi/mg), respectively. Immunoreactivity of radiolabeled OST7-G4-(1B4M){sub 43} and OST7-1B4M, as determined by the binding to KT005 cells expressing the antigen, was respectively 91% and 84% of that of {sup 125}I-labelled OST7. Biodistribution studies for preparations with maximum specific activity in normal mice 3 h after injection showed that {sup 111}In- or {sup 153}Gd-OST7-G4-(1B4M){sub 43} cleared faster from the blood and accumulated more in the liver than did {sup 111}In- or {sup 153}Gd-OST7-1B4M. The dendrimer 1B4M [G4-(1B4M){sub 64}] itself showed similar saturation effects with metals. The radioactivity in all the other organs reflected the rapid clearance of radioactivity from the blood. {sup 153}Gd-OST7-G4-(1B4M){sub 43} showed specific accumulation in the KT005 tumor. In conclusion, we could successfully bind 49 times as many metal atoms to an antibody molecule as is possible with conventional metal labeling for

  11. Technetium-99m direct radiolabeling of monoclonal antibody ior egf/r3

    Energy Technology Data Exchange (ETDEWEB)

    Morales, Alejo A. Morales; Crespo, Francisco Zayas; Gandolff, Gilda Nunez; Escobar, Normando Iznaga; Perez, Niuvis Perez; Hernandez, Juan C. Izquierdo

    1998-01-01

    Monoclonal antibodies (MAbs) are being widely used for imaging studies, coupled mainly with {sup 99m}Tc. The antibody ior egf/r3 is a MAb against human epidermal growth factor receptor (hEGF-r), and we have developed a method for optimum labeling of this MAb with {sup 99m}Tc. The reduction was performed with 2-mercaptoethanol (2-ME) at a molar ratio of 2000:1 (2-ME:MAb) and methylene diphosphonate as transchelant. The integrity of reduced MAb was checked by mean of native polyacrylamide gel electrophoresis (PAGE) and gel filtration chromatography on Superose 12 (purity >99%). Radio colloids remained lower than 2%, and the labeling efficiency was 98.5%. The number of sulfhydryl groups generated was quantified using Ellman's reagent and was found to be 6.65 {+-} 0.69 per antibody molecule. In vitro stability studies in several challenging conditions (DTPA, human serum albumin and human serum) were performed, and no significant loss in binding percentage was seen. Radio receptor assay was used to test immunoreactivity of the reduced MAb. Both labeled and unlabeled MAbs were able to compete for binding to the hEGF-r with radioiodinated EGF. Biodistribution studies in BALB/c mice are reported.

  12. Technetium-99m direct radiolabeling of monoclonal antibody ior egf/r3

    International Nuclear Information System (INIS)

    Morales, Alejo A. Morales; Crespo, Francisco Zayas; Gandolff, Gilda Nunez; Escobar, Normando Iznaga; Perez, Niuvis Perez; Hernandez, Juan C. Izquierdo

    1998-01-01

    Monoclonal antibodies (MAbs) are being widely used for imaging studies, coupled mainly with 99m Tc. The antibody ior egf/r3 is a MAb against human epidermal growth factor receptor (hEGF-r), and we have developed a method for optimum labeling of this MAb with 99m Tc. The reduction was performed with 2-mercaptoethanol (2-ME) at a molar ratio of 2000:1 (2-ME:MAb) and methylene diphosphonate as transchelant. The integrity of reduced MAb was checked by mean of native polyacrylamide gel electrophoresis (PAGE) and gel filtration chromatography on Superose 12 (purity >99%). Radio colloids remained lower than 2%, and the labeling efficiency was 98.5%. The number of sulfhydryl groups generated was quantified using Ellman's reagent and was found to be 6.65 ± 0.69 per antibody molecule. In vitro stability studies in several challenging conditions (DTPA, human serum albumin and human serum) were performed, and no significant loss in binding percentage was seen. Radio receptor assay was used to test immunoreactivity of the reduced MAb. Both labeled and unlabeled MAbs were able to compete for binding to the hEGF-r with radioiodinated EGF. Biodistribution studies in BALB/c mice are reported

  13. Localization of radiolabeled anti-DNA monoclonal antibodies in murine systemic lupus erythematosus (SLE)

    International Nuclear Information System (INIS)

    Wahl, R.; Hahn, B.; Ebling, F.

    1984-01-01

    The diagnosis of SLE can be extremely difficult. This multi-system disease is characterized by the deposition of DNA-anti-DNA antibody (Ab) complexes in many tissues, producing glomerulonephritis and systemic vasculitis. This study evaluates an IGG monoclonal (Mo) Ab directe3d against DNA (MrSSl) for potential radioimmunodiagnosis of SLE. Six 15 wk. old F-1 female hybrids of NZB+NZW mice (an animal SLE model that develops vasculitis and nephritis) were injected with 50 μCl of I-131 MrSSl and 15 μCl of I-125 isotype-matched control mouse myeloma (LPC-1) (non-reactive with DNA). Imaging and tissue distribution were studied. Two animals were also imaged using I-131 LPC Ab. Images at 2 and 9 days showed no clear differences in scan patterns using MrSSl or LPC-1 Ab. Tissue distribution studies at six days, however, showed a significantly higher accumulation of MrSSl in the kidneys vs. control Ab (2.7% vs. 1.8% of injected dose) (p < .04). Similarly, higher levels of MrSS were also seen in the spleen, liver and lungs (p < .03). Blood levels tended to be higher with the specific antibody as well. These differences were not apparent at 3 days post injection. The increased concentration of MrSSl present at 9 days in several organs may be secondary to MrSSl binding to DNA containing immune complexes present in diseased tissues. Blocked clearance by immune complexes or DNA, or differences in electrical charges of the antibodies could be contributing to the higher MrSSl levels seen. Images did not suggest deiodination as responsible. Further studies are necessary to determine if the amount of MrSSl retained by diseased animals is indicative of SLE disease activity

  14. Cloning and sequencing of V genes from anti-osteosarcoma monoclonal antibodies TP-1 and TP-3: Location of lysine residues and implications for radiolabeling

    International Nuclear Information System (INIS)

    Olafsen, Tove; Bruland, Oeyvind S.; Zalutsky, Michael R.; Sandlie, Inger

    1995-01-01

    Monoclonal antibodies TP-1 and TP-3 are of potential utility for the radioimmunodiagnosis of osteosarcoma in both human and canine patients. The V genes of these antibodies were cloned and sequenced and to facilitate radiolabeling of these proteins, the location of the lysine residues within these sequences have been determined. The V-domains of TP-1 contain a total of 12 lysines, 10 in the framework region and 2 in the CDR region, while the V-domains of TP-3 contain a total of 14 lysines, 11 in the framework region and 3 in the CDR regions. Using space-filling models, the availability of each lysine residue for radiolabeling, and potential interference with antigen binding was predicted

  15. Cloning and sequencing of V genes from anti-osteosarcoma monoclonal antibodies TP-1 and TP-3: Location of lysine residues and implications for radiolabeling

    Energy Technology Data Exchange (ETDEWEB)

    Olafsen, Tove; Bruland, Oeyvind S.; Zalutsky, Michael R.; Sandlie, Inger

    1995-08-01

    Monoclonal antibodies TP-1 and TP-3 are of potential utility for the radioimmunodiagnosis of osteosarcoma in both human and canine patients. The V genes of these antibodies were cloned and sequenced and to facilitate radiolabeling of these proteins, the location of the lysine residues within these sequences have been determined. The V-domains of TP-1 contain a total of 12 lysines, 10 in the framework region and 2 in the CDR region, while the V-domains of TP-3 contain a total of 14 lysines, 11 in the framework region and 3 in the CDR regions. Using space-filling models, the availability of each lysine residue for radiolabeling, and potential interference with antigen binding was predicted.

  16. Radiolabelled cellular blood elements

    International Nuclear Information System (INIS)

    Sinzinger, H.

    1990-01-01

    This book reports on radiolabelled cellular blood elements, covering new advances made during the past several years, in particular the use of Tc-99 as a tracer for blood elements. Coverage extends to several radiolabelled monoclonal antibodies that are specific for blood components and may label blood elements in vivo

  17. The binding parameters of radiolabelled monoclonal F (ab')2 and Fab' fragments relative to immunoglobulin G in reactions with surface-bound antigens

    International Nuclear Information System (INIS)

    Fjeld, J.G.; Nustad, K.; Michaelsen, T.E.

    1992-01-01

    The binding parameters of iodine-125-labelled intact monoclonal immunoglobulin G (IgG), F(ab') 2 and Fab' fragments were compared. The study was carried out with the two monoclonal antibodies (MoAbs) K13 and K16 specific for human Ig light chains κ and λ, respectively. When testing the 125 I-MoAbs against monodisperse polymer particles coated with the specific antigens, the K a for the F(ab') 2 fragments were similar to that for IgG, while the K a for the Fab' fragments were reduced to 10%-20% of that for IgG. The number N of effective target sites revealed with Fab' was higher than with F(ab') and IgG, presumably because less surface area is occupied by the small Fab' molecules. The immunoreactive fraction F ranged according to IgG>F(ab') 2 >Fab'. The explanation of the moderate difference between the K a of the monoclonal Fab' and the divalent IgG and F(ab') 2 was that the divalent molecules were not divalently attached to the particles. When testing the same antibody preparations against humanlymphoma cells producing Ig with light chains κ or λ, the binding results were less reliable than when particles were utilised, presumably due to antigen shedding. Different MoAbs vary in their loss of immunoreactivity due to enzymatic degradation and the radiolabelling procedure. The preparation of the radiolabelled fragments should therefore be optimized for each MoAb, and evaluation is necessary before injection. Artificial targets with a low leakage of antigen, like the monodisperse polymer particles here applied, are recommended for the in vitro evaluation of the immunoreactivity of labelled MoAb preparations. (orig.)

  18. Enavatuzumab, a Humanized Anti-TWEAK Receptor Monoclonal Antibody, Exerts Antitumor Activity through Attracting and Activating Innate Immune Effector Cells

    Directory of Open Access Journals (Sweden)

    Shiming Ye

    2017-01-01

    Full Text Available Enavatuzumab is a humanized IgG1 anti-TWEAK receptor monoclonal antibody that was evaluated in a phase I clinical study for the treatment of solid malignancies. The current study was to determine whether and how myeloid effector cells were involved in postulated mechanisms for its potent antitumor activity in xenograft models. The initial evidence for a role of effector cells was obtained in a subset of tumor xenograft mouse models whose response to enavatuzumab relied on the binding of Fc of the antibody to Fcγ receptor. The involvement of effector cells was further confirmed by immunohistochemistry, which revealed strong infiltration of CD45+ effector cells into tumor xenografts in responding models, but minimal infiltration in nonresponders. Consistent with the xenograft studies, human effector cells preferentially migrated toward in vivo-responsive tumor cells treated by enavatuzumab in vitro, with the majority of migratory cells being monocytes. Conditioned media from enavatuzumab-treated tumor cells contained elevated levels of chemokines, which might be responsible for enavatuzumab-triggered effector cell migration. These preclinical studies demonstrate that enavatuzumab can exert its potent antitumor activity by actively recruiting and activating myeloid effectors to kill tumor cells. Enavatuzumab-induced chemokines warrant further evaluation in clinical studies as potential biomarkers for such activity.

  19. 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

  20. Antibody guided diagnosis and therapy of brain gliomas using radiolabeled monoclonal antibodies against epidermal growth factor receptor and placental alkaline phosphatase

    International Nuclear Information System (INIS)

    Kalofonos, H.P.; Pawlikowska, T.R.; Hemingway, A.

    1989-01-01

    Twenty-seven patients with brain glioma were scanned using 123 I-labeled monoclonal antibodies against epidermal growth factor receptor (EGFR1) or placental alkaline phosphatase (H17E2). Successful localization was achieved in 18 out of 27 patients. Eleven out of 27 patients were also studied using a nonspecific control antibody (11.4.1) of the same immunoglobulin subclass and observable tumor localization was also achieved in five patients. The specificity of targeting was assessed by comparing images obtained with specific and nonspecific antibodies and by examining tumor and normal tissue biopsies after dual antibody administration. Ten patients with recurrent grade III or IV glioma who showed good localization of radiolabeled antibody were treated with 40-140 mCi of 131 I-labeled antibody delivered to the tumor area intravenously (n = 5) or by infusion into the internal carotid artery (n = 5). Six patients showed clinical improvement lasting from 6 mo to 3 yr. One patient continues in remission (3 yr after therapy), but the other five who responded initially relapsed 6-9 mo after therapy and died. No major toxicity was attributable to antibody-guided irradiation. Targeted irradiation by monoclonal antibody may be clinically useful and should be explored further in the treatment of brain gliomas resistant to conventional forms of treatment

  1. In vivo localization of radiolabeled monoclonal antibody to carcinoembryonic antigen (CEA) in a CEA-producing tumor

    International Nuclear Information System (INIS)

    Kamei, Tetsuya; Seto, Hikaru; Taki, Kuniyasu; Soya, Toshio; Kakishita, Masao; Maeda, Masatoshi; Honda, Takashi; Koshimura, Saburou.

    1987-01-01

    To compare accumulation of the 125 I-labeled antibodies(anti-carcinoembryonic antigen(CEA) monoclonal antibody and polyclonal antibody) to a CEA-producing tumor (SC-2-JCK), an in vivo localization study was performed in nude mice. The tumor-to-blood ratio at 120 hours after injection rose to 4.6 for the monoclonal antibody, but remained at 1.3 for the polyclonal antibody. However, no differences were noted between the antibodies up to 72 hours after injection. In autoradiograms, selective accumulation of the tracer was noted in the tumor for both antibodies. However, no superiority or inferiority of imaging for either of the antibodies could be definitely determined. (author)

  2. Detection of human cancer in an animal model using radio-labelled tumour-associated monoclonal antibodies

    International Nuclear Information System (INIS)

    Epenetos, A.A.; Arklie, J.; Knowles, R.W.; Bodmer, W.F.

    1982-01-01

    Monoclonal antibodies to epithelial-cell antigenic determinants, labelled with 123 I and 125 I, were administered parenterally to immunodeficient mice bearing human tumours derived from a human cancer cell line. Anterior, posterior and lateral radioscans of the body were taken with a gamma scintillation camera at various times from immediately to 65 days after injection. Visual displays of the images were processed by standard computer techniques. The model used a human colon-cancer cell line, HT29, and the monoclonal antibody, AUAl, which is specific to an epithelial proliferating antigen. Tumour detection was achieved in all the mice. The smallest tumour detectable appeared to be about 1 mm in diameter. The degree of antibody uptake in a tumour depended on its size and the blood supply of its surrounding tissues. (author)

  3. Radiolabelled monoclonal antibodies against alpha-fetoprotein for in vivo localization of human hepatocellular carcinoma by immunotomoscintigraphy

    International Nuclear Information System (INIS)

    Bergmann, J.F.; Lumbroso, J.D.; Manil, L.; Saccavini, J.C.; Rougier, P.; Assicot, M.; Mathieu, A.; Bellet, D.; Bohuon, C.

    1987-01-01

    Two high affinity monoclonal antibodies, designated AF01 and AF04, directed against distinct epitopes of human alpha-fetoprotein (AFP) and the Fab fragments of one of them, were labelled with 131 I and injected into 18 patients with AFP producing hepatocellular carcinoma (HCC) in order to carry out imaging studies by tomoscintigraphy. Twelve patients were injected with whole antibody, only three of seven patients injected with AF01 and two of five patients injected with AF04 had a positive scan. In contrast, five out of six patients injected with labelled Fab fragments of AF04 had positive imaging. These results confirm that tumour imaging of HCC using 131 I labelled monoclonal antibody against AFP is feasible. Moreover, utilization of tomoscintigraphy in place of linear scintigraphy and Fab fragments instead of whole immunoglobulin may improve the sensitivity of radioimmunolocalization. This technique provides useful information on the in vivo distribution of monoclonal antibodies directed against AFP and on the practicability of the eventual therapeutic use of anti-AFP antibodies in HCC. (orig.)

  4. Immunoscintigraphy of human tumors transplanted in nude mice with radiolabeled anti-ras p21 monoclonal antibodies

    International Nuclear Information System (INIS)

    Katoh, Y.; Nakata, K.; Kohno, K.; Shima, M.; Satoh, A.; Kusumoto, Y.; Ishii, N.; Kohji, T.; Shiku, H.; Nagataki, S.

    1990-01-01

    Anti-ras p21 monoclonal antibody (RASK-3) was used for immunoscintigraphy of human cancer cell lines in nude mice. Iodine-125-labeled RASK-3 was injected into nude mice with either human colon cancers (FCC-1 or BM-314) or lung cancer (KNS-62). Clear images were obtained in all three cancers 7 days after the injection of antibody. No localization of 125 I-labeled control monoclonal antibody was observed. The ratio of tissue/blood radioactivity and % ID/g in the tumor were significantly higher than other organs by Day 8. The specific localization index examined by 131 I-RASK-3 and 125 I-control monoclonal antibody was also higher in the tumor than in other tissues. In the in vitro study, binding of RASK-3 to tumor cells increased significantly by treatment of cells with either lysolecithin or periodate-lysine-paraformaldehyde, which confirmed the intracellular localization of ras p21. The mechanism by which anti-ras p21 antibodies accumulate in tumor sites could be the necrotic changes in tumor cells or changes in membrane permeability of non-necrotic cells. These results provide a strong rationale for the utilization of ras p21 as a target antigen in the imaging of a variety of human cancers

  5. C-kit-targeted imaging of gastrointestinal stromal tumor using radiolabeled anti-c-kit monoclonal antibody in a mouse tumor model

    International Nuclear Information System (INIS)

    Sogawa, Chizuru; Tsuji, Atsushi B.; Sudo, Hitomi; Sugyo, Aya; Yoshida, Chisato; Odaka, Kenichi; Uehara, Tomoya; Arano, Yasushi; Koizumi, Mitsuru; Saga, Tsuneo

    2010-01-01

    Introduction: Gastrointestinal stromal tumor (GIST) is the most common mesenchymal tumor arising from the gastrointestinal tract and highly expresses mutated c-kit. We aimed to develop a specific and sensitive method for detecting GISTs using radiolabeled anti-c-kit monoclonal antibody. Methods: A mutated c-kit-expressing cell clone was established by transfecting an expressing vector of mutated c-kit gene into HEK293 human embryonic kidney cells. The tumors were developed by inoculating c-kit-expressing cells into nude mice. 125 I- and 111 In-labeled anti-c-kit antibodies (12A8 and 41A11) were evaluated in vitro by cell binding, competitive inhibition and cellular internalization assays, and in vivo by biodistribution and imaging studies in tumor-bearing mice. Results: Both 125 I- and 111 In-labeled antibodies showed specific binding with c-kit-expressing cells with high affinity (dissociation constants = 2.2-7.1x10 9 M -1 ). Internalization assay showed that 125 I-labeled antibodies were rapidly internalized and dehalogenated, with the release of 125 I from the cells, resulting in reduction of cell-associated radioactivity with time. In contrast, 111 In-labeled antibody was internalized but did not result in the reduced radioactivity associated with tumor cells. Reflecting this phenomenon, the in vivo tumor uptake of 125 I-labeled antibody was low on Day 1, further decreasing with time, while tumor uptake of 111 In-labeled antibody was high on Day 1, further increasing with time. The xenografted tumor was clearly visualized by scintigraphy after injection of 111 In-labeled antibody. Conclusion: The anti-c-kit monoclonal antibody labeled with a metal radionuclide would be promising for c-kit-targeted imaging of GISTs.

  6. In vitro and in vivo tumor models for studies of distribution of radiolabelled monoclonal antibodies and fragments

    International Nuclear Information System (INIS)

    Buchegger, F.; Halpern, S.E.; Sutherland, R.M.; Schreyer, M.; Mach, J.P.; Rochester Univ., NY

    1986-01-01

    Colon carcinoma multicellular spheroids were incubated in vitro with radiolabelled MAbs. The more rapid penetration of fragments as compared to intact MAbs was clearly demonstrated. For the study of antibody localization in tumors in vivo, the model of nude mice with ligated kidneys was used. Although very artificial, this model allowed to demonstrate that, without urinary excretion, Fab fragments accumulated more rapidly into the tumor than intact MAbs and disappeared faster from the blood. This difference was less striking for F(ab') 2 fragments. In the liver a decreased accumulation of both types of fragments as compared to intact MAbs was observed. Concerning radio-immunotherapy we think that Fab fragments are not useful because of their too short half-life the circulation and in tumor and because they will probably be too toxic for the kidneys. Intact MAbs and F(ab') 2 fragments have each their advantages. Intact MAbs show highest tumor accumulation in mice without ligated kidney, however, they remain mostly on the periphery of tumor nodules, as shown by autoradiography. F(ab') 2 fragments have been found to penetrate deeper into the tumor and to accumulate less in the liver. It might be therefore an advantage to combine intact MAbs with F(ab') 2 fragments, so that in the tumor two different regions could be attacked whereas in normal tissues toxicity could be distributed to different organs such as to the liver with intact MAbs and to the kidney with F(ab') 2 fragments. (orig.) [de

  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. In vitro characterization of 177Lu-radiolabelled chimeric anti-CD20 monoclonal antibody and a preliminary dosimetry study

    International Nuclear Information System (INIS)

    Forrer, Flavio; Mueller-Brand, Jan; Chen, Jianhua; Fani, Melpomeni; Powell, Pia; Maecke, Helmut R.; Lohri, Andreas; Moldenhauer, Gerhard

    2009-01-01

    131 I- and 90 Y-labelled anti-CD20 antibodies have been shown to be effective in the treatment of low-grade, B-cell non-Hodgkin's lymphoma (NHL). However, the most appropriate radionuclide in terms of high efficiency and low toxicity has not yet been established. In this study we evaluated an immunoconjugate formed by the anti-CD20 antibody rituximab and the chelator DOTA (1,4,7,10-tetraazacyclododecane-1,4,7,10-tetraacetic acid). DOTA-rituximab was prepared as a kit formulation and can be labelled in a short time ( 177 Lu or 90 Y. Immunoconjugates with different numbers of DOTA molecules per rituximab were prepared using p-SCN-Bz-DOTA. In vitro immunoreactivity and stability were tested and preliminary dosimetric results were acquired in two patients. The immunological binding properties of DOTA-rituximab to the CD20 antigen were found to be retained after conjugation with up to four chelators. The labelled product was stable against a 10 5 times excess of diethylenetriaminepentaacetic acid (DTPA, 37 C, 7 days). Two patients with relapsed NHL were treated with 740 MBq/m 2 body surface 177 Lu-DOTA-rituximab. Scintigraphic images showed specific uptake at tumour sites and acceptable dosimetric results. The mean whole-body dose was found to be 314 mGy. The administration of 177 Lu-DOTA-rituximab was tolerated well. Our results show that DOTA-rituximab (4:1) can be labelled with 177 Lu with sufficient stability while the immunoconjugate retains its immunoreactivity. 177 Lu-DOTA-rituximab is an interesting, well-tolerated radiolabelled antibody with clinical activity in a low dose range, and provides an approach to the efficient treatment with few side effects for patients with relapsed NHL. (orig.)

  9. Preparation and radiolabeling of humanized anti-HER1 monoclonal antibody nimotuzumab Fab' fragment with 68Ga and 90Y

    International Nuclear Information System (INIS)

    Alonso Martinez, L. M.; Xiques Castillo, A.; Leyva Montanna, R.; Perez-Malo Cruz, M.; Zamora Barrabi, M.; Manresa Sanchez, Y.

    2013-01-01

    Antibody-based targeted delivery of radioisotopes to malignant tissues is a promising approach in cancer diagnostics and therapy. However, intact antibody molecules are large glycoproteins (∼150 kDa) that have limited application in molecular imaging and therapy due to their relatively slow clearance from the circulation leading to a high background signal rather both cases the sensitivity can be increased with the use of enzymatically produced Fab' fragments. In this work, the ability to get labeled with 62 Ga and 90 Y of a monoclonal antibody (mAb) Fab' fragment against the transmembrane receptor tyrosine kinase HER-1 was studied for future applications in PET imaging and radioimmunotherapy of tumors. In order to obtain the Fab' fragment the mAb was cleaved with pepsin in molar excess. After separating the reaction mixture in two steps using affinity and ion-exchange chromatography, the Fab' fragment was finally obtained by reduction of the F(ab') 2 with a molar excess of 2-mercaptoethanol followed by a size exclusion purification step. The Fab' fragment was derivatized with 1,4,7,10-tetraaza cyclododecane-1,4,7,10-tetraacetic acid mono N-hydroxysuccinimide commercial ester (DOTA-NHS-ester) applying a simple procedure and the number of DOTA groups linked to Fab' were determinate. The labeling of the conjugate with 68 Ga and 90 Y from 'in-house generators yielded radiochemically pure probes that can become a suitable radioimmunoconjugated in a near future. (Author)

  10. 99mTc-monoclonal antibody radiolabeled via hydrazino nicotinamide derivative for imaging disialoganglioside GD2-positive tumors

    International Nuclear Information System (INIS)

    Fonti, Rosa; Cheung, N.-K.V.; Bridger, Gary J.; Guo, H.-F.; Abrams, Michael J.; Larson, Steven M.

    1999-01-01

    3F8 is a murine IgG 3 monoclonal antibody (MAb) selective for the ganglioside G D2 . Previous studies using 131 I-3F8 have shown great potential in the imaging of neuroectodermal tumors and the therapy of human neuroblastoma. 131 I is commonly used in radioimmunodiagnosis, but its relatively long half-life (8 days) and its high energy γ-emission (364 KeV) are suboptimal for imaging purposes when compared with 99m Tc (6 h and 140 KeV, respectively). To label 3F8 with 99m Tc, the antibody was first coupled with a heterobifunctional linker, succinimidyl-6-hydrazinonicotinate hydrochloride (SHNH), obtaining a hydrazinonicotinamide-antibody conjugate. Using 99m Tc-Tricine as the precursor complex, 3F8-SHNH was coupled efficiently to 99m Tc, resulting in >90% radiometal incorporation, with a specific activity >10 mCi/mg and retaining full immunoreactivity. Immunoscintigraphy at 6, 22, and 46 h after intravenous injection of 1 mCi of 99m Tc-3F8 showed selective neuroblastoma localization in xenografted nude mice, comparable to that obtained with the injection of 100 μCi of 131 I-3F8. Biodistribution studies of 131 I-3F8 and 99m Tc-3F8 in mice demonstrated comparable %ID/g uptake in tumor (with a T/B ratio: ∼2.5 at 24 h and ∼3.5 at 48 h) and normal organs, including blood, except for spleen and liver which had about a three times higher uptake of the 99m Tc conjugate. In conclusion, 99m Tc can be coupled conveniently at high specific activity to 3F8 without compromising immunoreactivity. SHNH appears to be a useful linker for 99m Tc in tumor diagnostic imaging and may have potential utility in coupling other radioisotopes (e.g., 94m Tc) for positron imaging and therapy

  11. Radiolabeled monoclonal antibody 15 and its fragments for localization and imaging of xenografts of human lung cancer

    International Nuclear Information System (INIS)

    Endo, K.; Kamma, H.; Ogata, T.

    1988-01-01

    Monoclonal antibody (MAb) 15 and its F(ab')2 and Fab fragments were radioiodinated, and their biodistribution and imaging were compared in BALB/c nude mice bearing a xenograft of a human lung cancer (TKB-2). Association constants for 125I-labeled MAb 15 IgG, F(ab')2, and Fab were 1.9 X 10(9), 1.8 X 10(9), and 3.7 X 10(8) M-1, respectively. Immunoreactive fractions ranged from 0.59 to 0.50. Cultured TKB-2 cells expressed 1.1 X 10(4) binding sites/cell for MAb 15 IgG in vitro. The binding of a control antibody and the binding of its fragments to TKB-2 cells were less than 3% of the input doses. The mice with the TKB-2 tumors were given simultaneous injections of 10 microCi of 131I-labeled MAb 15 or its fragments and 10 microCi of 125I-labeled control IgG or its fragments. With MAb 15 IgG, the percentage of the injected dose bound per gram of tissue (ID/g) of the tumor was 3.68% at day 7, when the localization index (LI) was 4.38. At day 2 after MAb 15 F(ab')2 injection, 1.12% of the ID/g was localized in the tumor and the LI was 3.04. After MAb 15 Fab injection, the percentage of the ID/g of the tumor was 0.31% and the LI was 2.58 at day 1. MAb 15 IgG, F(ab')2, and Fab cleared from the blood early, with a half-life of 33, 16, and 9 hours, respectively. The distributions of MAb 15 and its fragments in the normal organs did not differ from those of the control. Radioimaging with 100 microCi of 131I-labeled MAb 15 and its fragments showed that 42%, 44%, and 32% of the total-body count were localized in the tumor with IgG at day 7, F(ab')2 at day 2, or Fab at day 1, respectively. Because the radioactivity remaining in the tumor with Fab was low, the image was insufficient. Throughout the period, less than 10% of the control IgG and its fragments remained in the tumor. Microautoradiography confirmed the binding of MAb 15 and its fragments to the tumor cells

  12. Radiolabeled antibody imaging

    International Nuclear Information System (INIS)

    Wahl, R.L.

    1987-01-01

    Radiolabeled antibodies, in particular monoclonal antibodies, offer the potential for the specific nuclear imaging of malignant and benign diseases in man. If this imaging potential is realized, they may also have a large role in cancer treatment. This paper reviews: (1) what monoclonal antibodies are and how they differ from polyclonal antibodies, (2) how they are produced and radiolabeled, (3) the results of preclinical and clinical trials in cancer imaging, including the utility of SPECT and antibody fragments, (4) the role of antibodies in the diagnosis of benign diseases, (5) alternate routes of antibody delivery, (6) the role of these agents in therapy, and (7) whether this technology ''revolutionizes'' the practice of nuclear radiology, or has a more limited complementary role in the imaging department

  13. Antiglycopeptide Mouse Monoclonal Antibody LpMab-21 Exerts Antitumor Activity Against Human Podoplanin Through Antibody-Dependent Cellular Cytotoxicity and Complement-Dependent Cytotoxicity.

    Science.gov (United States)

    Kato, Yukinari; Kunita, Akiko; Fukayama, Masashi; Abe, Shinji; Nishioka, Yasuhiko; Uchida, Hiroaki; Tahara, Hideaki; Yamada, Shinji; Yanaka, Miyuki; Nakamura, Takuro; Saidoh, Noriko; Yoshida, Kanae; Fujii, Yuki; Honma, Ryusuke; Takagi, Michiaki; Ogasawara, Satoshi; Murata, Takeshi; Kaneko, Mika K

    2017-02-01

    The interaction between podoplanin (PDPN) and C-type lectin-like receptor 2 (CLEC-2) is involved in tumor malignancy. We have established many monoclonal antibodies (mAbs) against human podoplanin using the cancer-specific mAb (CasMab) technology. LpMab-21, one of the mouse antipodoplanin mAbs, is of the IgG 2a subclass, and its minimum epitope was determined to be Thr76-Arg79 of the human podoplanin. Importantly, sialic acid is linked to Thr76; therefore, LpMab-21 is an antiglycopeptide mAb (GpMab). In this study, we investigated whether LpMab-21 shows antibody-dependent cellular cytotoxicity (ADCC) and complement-dependent cytotoxicity (CDC) against human podoplanin-expressing cancer cell lines in vitro and also studied its antitumor activities using a xenograft model. LpMab-21 showed high ADCC and CDC activities against not only podoplanin-expressing Chinese hamster ovary cells but also LN319 glioblastoma cells and PC-10 lung cancer cells, both of which endogenously express podoplanin. Furthermore, LpMab-21 decreased tumor growth in vivo, indicating that LpMab-21 could be useful for antibody therapy against human podoplanin-expressing cancers.

  14. Novel anti-Sialyl-Tn monoclonal antibodies and antibody-drug conjugates demonstrate tumor specificity and anti-tumor activity.

    Science.gov (United States)

    Prendergast, Jillian M; Galvao da Silva, Ana Paula; Eavarone, David A; Ghaderi, Darius; Zhang, Mai; Brady, Dane; Wicks, Joan; DeSander, Julie; Behrens, Jeff; Rueda, Bo R

    Targeted therapeutics that can differentiate between normal and malignant tumor cells represent the ideal standard for the development of a successful anti-cancer strategy. The Sialyl-Thomsen-nouveau antigen (STn or Sialyl-Tn, also known as CD175s) is rarely seen in normal adult tissues, but it is abundantly expressed in many types of human epithelial cancers. We have identified novel antibodies that specifically target with high affinity the STn glycan independent of its carrier protein, affording the potential to recognize a wider array of cancer-specific sialylated proteins. A panel of murine monoclonal anti-STn therapeutic antibodies were generated and their binding specificity and efficacy were characterized in vitro and in in vivo murine cancer models. A subset of these antibodies were conjugated to monomethyl auristatin E (MMAE) to generate antibody-drug conjugates (ADCs). These ADCs demonstrated in vitro efficacy in STn-expressing cell lines and significant tumor growth inhibition in STn-expressing tumor xenograft cancer models with no evidence of overt toxicity.

  15. A microscale synthesis of a promising radiolabelled antitumor drug: cis-1,1-cyclobutanedicarboxylato (2R)-2-methyl-1,4-butanediamine platinum(II), NK121

    International Nuclear Information System (INIS)

    Suwa, Masato; Kogawa, Osamu; Hashimoto, Yutaka

    1992-01-01

    A promising antitumor drug, cis-1,1-cyclobutane-dicarboxylato (2R)-2-methyl-1,4-butanediamine platinum (II), NK121, was synthesized from radionuclides of platinum such as 193m Pt, 195m Pt and 191 Pt which were produced by neutron irradiation of enriched 192 Pt. The overall yield was 38.6% in a synthesis time of 10 hours. The radioactivities present in 8.39 mg of NK121 were 115.3 μCi as 193m Pt, 29.9 μCi as 197 Pt, 22.0 μCi as 195m Pt, and 4.8 μCi as 191 Pt at the end of synthesis. The specific activity of the NK121 was 13.7 μCi ( 193m Pt)/mg NK121 at the end of synthesis. The radiochemical purity of NK121 was typically 99%. HPLC analyses confirmed that NK121 was in an adequate chemical purity and suitable for animal experimentation. (author)

  16. A microscale synthesis of a promising radiolabelled antitumor drug: cis-1,1-cyclobutanedicarboxylato (2R)-2-methyl-1,4-butanediamine platinum(II), NK121

    Energy Technology Data Exchange (ETDEWEB)

    Suwa, Masato; Kogawa, Osamu; Hashimoto, Yutaka (Nippon Kayaku Co. Ltd., Tokyo (Japan). Research Labs. of Pharmaceuticals Group); Nowatari, Hiroyoshi (Nippon Kayaku Co. Ltd., Takasaki, Gumma (Japan). Takasaki Research Labs.); Murase, Yuko; Homma, Yoshio (Kyoritsu Coll. of Pharmacy, Tokyo (Japan))

    1992-05-01

    A promising antitumor drug, cis-1,1-cyclobutane-dicarboxylato (2R)-2-methyl-1,4-butanediamine platinum (II), NK121, was synthesized from radionuclides of platinum such as {sup 193m}Pt, {sup 195m}Pt and {sup 191}Pt which were produced by neutron irradiation of enriched {sup 192}Pt. The overall yield was 38.6% in a synthesis time of 10 hours. The radioactivities present in 8.39 mg of NK121 were 115.3 {mu}Ci as {sup 193m}Pt, 29.9 {mu}Ci as {sup 197}Pt, 22.0 {mu}Ci as {sup 195m}Pt, and 4.8 {mu}Ci as {sup 191}Pt at the end of synthesis. The specific activity of the NK121 was 13.7 {mu}Ci ({sup 193m}Pt)/mg NK121 at the end of synthesis. The radiochemical purity of NK121 was typically 99%. HPLC analyses confirmed that NK121 was in an adequate chemical purity and suitable for animal experimentation. (author).

  17. In vitro characterization of {sup 177}Lu-radiolabelled chimeric anti-CD20 monoclonal antibody and a preliminary dosimetry study

    Energy Technology Data Exchange (ETDEWEB)

    Forrer, Flavio; Mueller-Brand, Jan [University Hospital Basel, Institute of Nuclear Medicine, Basel (Switzerland); Chen, Jianhua; Fani, Melpomeni; Powell, Pia; Maecke, Helmut R. [University Hospital Basel, Division of Radiological Chemistry, Basel (Switzerland); Lohri, Andreas [Basel University Medical Clinic, Liestal (Switzerland); Moldenhauer, Gerhard [German Cancer Research Center, Division of Molecular Immunology, Heidelberg (Germany)

    2009-09-15

    {sup 131}I- and {sup 90}Y-labelled anti-CD20 antibodies have been shown to be effective in the treatment of low-grade, B-cell non-Hodgkin's lymphoma (NHL). However, the most appropriate radionuclide in terms of high efficiency and low toxicity has not yet been established. In this study we evaluated an immunoconjugate formed by the anti-CD20 antibody rituximab and the chelator DOTA (1,4,7,10-tetraazacyclododecane-1,4,7,10-tetraacetic acid). DOTA-rituximab was prepared as a kit formulation and can be labelled in a short time (<20 min) with either {sup 177}Lu or {sup 90}Y. Immunoconjugates with different numbers of DOTA molecules per rituximab were prepared using p-SCN-Bz-DOTA. In vitro immunoreactivity and stability were tested and preliminary dosimetric results were acquired in two patients. The immunological binding properties of DOTA-rituximab to the CD20 antigen were found to be retained after conjugation with up to four chelators. The labelled product was stable against a 10{sup 5} times excess of diethylenetriaminepentaacetic acid (DTPA, 37 C, 7 days). Two patients with relapsed NHL were treated with 740 MBq/m{sup 2} body surface {sup 177}Lu-DOTA-rituximab. Scintigraphic images showed specific uptake at tumour sites and acceptable dosimetric results. The mean whole-body dose was found to be 314 mGy. The administration of {sup 177}Lu-DOTA-rituximab was tolerated well. Our results show that DOTA-rituximab (4:1) can be labelled with {sup 177}Lu with sufficient stability while the immunoconjugate retains its immunoreactivity. {sup 177}Lu-DOTA-rituximab is an interesting, well-tolerated radiolabelled antibody with clinical activity in a low dose range, and provides an approach to the efficient treatment with few side effects for patients with relapsed NHL. (orig.)

  18. Standardization of methodology to derivatization and radiolabeling of the anti-CD20 monoclonal antibody from bifunctional chelator DOTA-NHS-Ester

    International Nuclear Information System (INIS)

    Massicano, Adriana V.F.; Akanji, Akinkunmi G.; Santos, Josefina S.; Pujatti, Priscilla B.; Couto, Renata M.; Massicano, Felipe; Araujo, Elaine Bortoleti de

    2009-01-01

    Lymphomas are cancers of the lymphatic system, being the most common the non-Hodgkin lymphoma (NHL). The Radioimmunotherapy (RIT), that increase the cytotoxic effect of monoclonal antibodies (mAb), therefore labeling these Mab with different radioisotopes. RIT combines the specificity of the antibody and the toxicity of the radionuclides. The mAb anti-CD20 is used for treatment of relapse or refractory NHL. The labeling of anti- CD20 with 177 Lu, requires a bifunctional chelating agent that is designed to make a 'connect bridge' between the mAb and the radionuclide. The incorporation of the chelating group in mAb structure is called derivatization. The aim of this work is to study the derivatization of anti-CD20 antibody with DOTA-NHS-ester chelating group and labeling parameters to produce 177 Lu-DOTA-Anti CD20. Five milligrams of anti-CD20 were purified by dialysis against phosphate buffer pH 8.0 and derivatized with DOTA-NHS-ester in 1:250, 1:500 and 1:1000 molar ratios. The reaction was conducted for 1 hour in gently mixing at room temperature and remained under refrigeration for 48 hours. The reaction mixture was purified in gel column Sephadex G-50 ; the aliquots that presented greater protein concentration, were mixed and concentrated. The purified antibody conjugated was added to 111-185MBq (3-5mCi) of 177 LuCl3 diluted in 0.4 M acetate buffer pH 5.5. Radiochemical purity was less than 95% in all the molar ratios, indicating necessity of the purification after the labeling. The mAb derivatized showed stable when stored for to 1 month to 4 deg C and 4 days at -20 deg C. (author)

  19. 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

  20. The intratumoral distribution of radiolabeled 177Lu-BR96 monoclonal antibodies changes in relation to tumor histology over time in a syngeneic rat colon carcinoma model.

    Science.gov (United States)

    Örbom, Anders; Eriksson, Sophie E; Elgström, Erika; Ohlsson, Tomas; Nilsson, Rune; Tennvall, Jan; Strand, Sven-Erik

    2013-08-01

    The therapeutic effect of radioimmunotherapy depends on the distribution of the absorbed dose in relation to viable cancer cells within the tumor, which in turn is a function of the activity distribution. The aim of this study was to investigate the distribution of (177)Lu-DOTA-BR96 monoclonal antibodies targeting the Lewis Y antigen over 7 d using a syngeneic rat model of colon carcinoma. Thirty-eight tumor-bearing rats were intravenously given 25 or 50 MBq of (177)Lu-DOTA-BR96 per kilogram of body weight and were sacrificed 2, 8, 24, 48, 72, 96, 120, or 168 h after injection, with activity measured in blood and tumor samples. Adjacent cryosections of each tumor were analyzed in 3 ways: imaging using a silicon-strip detector for digital autoradiography, staining for histologic characterization, or staining to determine the distribution of the antigen, vasculature, and proliferating cells using immunohistochemistry. Absorbed-dose rate distribution images at the moment of sacrifice were calculated using the activity distribution and a point-dose kernel. The correlations between antigen expression and both activity uptake and absorbed-dose rate were calculated for several regions of interest in each tumor. Nine additional animals with tumors were given unlabeled antibody to evaluate possible immunologic effects. At 2-8 h after injection, activity was found in the tumor margins; at 24 h, in viable antigen-expressing areas within the tumor; and at 48 h and later, increasingly in antigen-negative areas of granulation tissue. The correlation between antigen expression and both the mean activity and the absorbed-dose rate in regions of interest changed from positive to negative after 24 h after injection. Antigen-negative areas also increased over time in animals injected with unlabeled BR96, compared with untreated tumors. The results indicate that viable Lewis Y-expressing tumor cells are most efficiently treated during the initial uptake period. The activity then seems

  1. Radiolabeled platelets

    International Nuclear Information System (INIS)

    Datz, F.L.; Taylor, A.T.

    1986-01-01

    Initial interest in developing techniques to radiolabel platelets was spurred by the lack of an accurate method for measuring platelet life span in both normals and in thrombocytopenic patients. Early investigators could obtain only rough estimates of platelet life spans by monitoring the platelet counts of thrombocytopenic patients undergoing platelet transfusions. Labels were also sought that would allow imaging of platelets in vivo in order to better understand the pathophysiology of atherosclerosis, thrombophlebitis, and clotting disorders, and to improve the clinical diagnosis of these diseases. Two types of platelet labels were investigated: cohort (pulse) labels and random labels. Cohort labels are taken up by megakaryocytes in the bone marrow and incorporated in the DNA and other components of the forming platelet. In theory, only freshly released platelets of a uniform age are labeled. Random labels, on the other hand, tag platelets in the peripheral blood, labeling platelets of all ages

  2. Targeting of human glioma xenografts in vivo utilizing radiolabeled antibodies

    International Nuclear Information System (INIS)

    Williams, J.A.; Wessels, B.W.; Wharam, M.D.; Order, S.E.; Wanek, P.M.; Poggenburg, J.K.; Klein, J.L.

    1990-01-01

    Radiolabeled antibodies provide a potential basis for selective radiotherapy of human gliomas. We have measured tumor targeting by radiolabeled monoclonal and polyclonal antibodies directed against neuroectodermal and tumor-associated antigens in nude mice bearing human glioma xenografts. Monoclonal P96.5, a mouse IgG2a immunoglobulin, defines an epitope of a human melanoma cell surface protein, and specifically binds the U-251 human glioma as measured by immunoperoxidase histochemistry. 111In-radiolabeled P96.5 specifically targets the U-251 human glioma xenograft and yields 87.0 microCuries (microCi) of tumor activity per gram per 100 microCi injected activity compared to 4.5 microCi following administration of radiolabeled irrelevant monoclonal antibody. Calculations of targeting ratios demonstrate deposited dose to be 11.6 times greater with radiolabeled P96.5 administration compared to irrelevant monoclonal antibody. The proportion of tumor dose found in normal organs is less than 10%, further supporting specific targeting of the human glioma xenograft by this antibody. Monoclonal antibody ZME018, which defines a second melanoma-associated antigen, and polyclonal rabbit antiferritin, which defines a tumor-associated antigen, demonstrate positive immunoperoxidase staining of the tumor, but comparatively decreased targeting. When compared to the 111In-radiolabeled antibody, 90Y-radiolabeled P96.5 demonstrates comparable tumor targeting and percentages of tumor dose found in normal organs. To test the therapeutic potential of 90Y-radiolabeled P96.5, tumors and normal sites were implanted with miniature thermoluminescent dosimeters (TLD). Seven days following administration of 100 microCi 90Y-radiolabeled P96.5, average absorbed doses of 3770, 980, 353, and 274 cGy were observed in tumor, liver, contralateral control site, and total body, respectively

  3. 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

  4. Antitumor efficacy of triple monoclonal antibody inhibition of epidermal growth factor receptor (EGFR) with MM151 in EGFR-dependent and in cetuximab-resistant human colorectal cancer cells

    Science.gov (United States)

    Napolitano, Stefania; Martini, Giulia; Martinelli, Erika; Della Corte, Carminia Maria; Morgillo, Floriana; Belli, Valentina; Cardone, Claudia; Matrone, Nunzia; Ciardiello, Fortunato; Troiani, Teresa

    2017-01-01

    Purpose We investigated the effect of triple monoclonal antibody inhibition of EGFR to overcome acquired resistance to first generation of anti-EGFR inhibitors. Experimental design MM151 is a mixture of three different monoclonal IgG1 antibodies directed toward three different, non-overlapping, epitopes of the EGFR. We performed an in vivo study by using human CRC cell lines (SW48, LIM 1215 and CACO2) which are sensitive to EGFR inhibitors, in order to evaluate the activity of MM151 as compared to standard anti-EGFR mAbs, such as cetuximab, as single agent or in a sequential strategy of combination MM151 with irinotecan (induction therapy) followed by MM151 with a selective MEK1/2 inhibitor (MEKi) (maintenance therapy). Furthermore, the ability of MM151 to overcome acquired resistance to cetuximab has been also evaluated in cetuximab-refractory CRC models. Results MM151 shown stronger antitumor activity as compared to cetuximab. The maintenance treatment with MM151 plus MEKi resulted the most effective therapeutic modality. In fact, this combination caused an almost complete suppression of tumor growth in SW48, LIM 1215 and CACO2 xenografts model at 30 week. Moreover, in this treatment group, mice with no evidence of tumor were more than double as compared to single agent treated mice. Its superior activity has also been demonstrated, in cetuximab-refractory CRC models. Conclusions These results provide experimental evidence that more efficient and complete EGFR blockade may determine better antitumor activity and could contribute to prevent and/or overcome acquired resistance to EGFR inhibitors. PMID:29137301

  5. Purification of immunoreactive radiolabeled moniclonal antibodies with anti-iodiotypic moniclonal antibodies

    International Nuclear Information System (INIS)

    Temponi, M.; Pupa, S.; Ferrone, S.

    1990-01-01

    A method is described to purify immunoreactive moniclonal antibodies from radiolabeled monoclonal antibody preparations. The method is based on incubation of radiolabeled monoclonal antibodies with insolubilized anti-idiotypic monoclonal antibodies to idiotopes within the antigen-combining site of monoclonal antibodies to be purified an elution of bound monoclonal antibodies with a low pH buffer. The immunoreactive fraction of the purified monoclonal antibodies was at least 82%; the yeald was at least 73%. The purification procedure did not cause any detectable change in the affinity constant of the eluted monoclonal antibodies. The method is simple and rapid; the requirement for anti-idiotypic monoclonal antibodies to idiotopes within the antigen-combining site of the antibodies to be purified is not likely to represent a major limitation in the broad application of the present method, since the hybridoma technology has greatly facilitated the development of anti-idiotypic monoclonal antibodies. (author). 12 refs.; 4 figs.; 1 tab

  6. Radiolabelled blood cells

    Energy Technology Data Exchange (ETDEWEB)

    Lavender, J.P.

    1986-12-01

    After the introduction of gamma-emitting labels for blood-cells the use of radio-labelled blood cells is not only limited to kinetics of blood cells but it is also possible to localise inflammations, abscesses and thrombus. The most commonly applied label for red cells is Tc-99m. The most widely used technique for labelling granulocytes or platelets is In-111-oxine. In future the labelling of blood cells will be more simple and more specific due to monoclonal antibodies onto the platelet or the granulocyte cell surface. Labelled red cells have their main application in blood-pool imaging and in localisation of gastrointestinal bleeding. Besides the determination of the platelet life-span in haematologic disorders labelled platelets allow to localise thrombus and to show abnormal vasculature in the rejecting kidney. The commonest application for In-111-oxin labelled granulocytes is to show abdominal inflammations to localise inflamed bowel segments and to assess the inflammatory activity in chronic inflammatory bowel diseases. Moreover brain abscesses, bone sepsis and lung sepsis can be identified.

  7. Towards tumour targeting with copper-radiolabelled macrocycle-antibody conjugates

    International Nuclear Information System (INIS)

    Morphy, J.R.; Parker, David; Kataky, Ritu

    1989-01-01

    Tetraaza-macrocycles covalently attached to a monoclonal antibody may be efficiently radiolabelled with 64 Cu or 67 Cu at pH4, minimising non-specific binding to the protein, giving a kinetically stable conjugate in vivo. (author)

  8. Radiolabelled sucralfate compositions

    International Nuclear Information System (INIS)

    Vasquez, T.E.; Bridges, R.L.; Braunstein, P.; Jansholt, A.

    1984-01-01

    A novel radiopharmaceutical composition comprising an aqueous solution or suspension containing a radiolabelled sucralfate or sucralfate derivative or precursor is claimed. The composition is effective for in vivo scintigraphic imaging of the gastrointestinal muscosal areas in humans. The sucralfate is combined with a radiolabelled albumin or other protein or protein derivative under acidic conditions

  9. Predominant antitumor effects by fully human anti-TRAIL-receptor2 (DR5) monoclonal antibodies in human glioma cells in vitro and in vivo

    Science.gov (United States)

    Nagane, Motoo; Shimizu, Saki; Mori, Eiji; Kataoka, Shiro; Shiokawa, Yoshiaki

    2010-01-01

    Tumor necrosis factor–related apoptosis-inducing ligand (TRAIL/Apo2 L) preferentially induces apoptosis in human tumor cells through its cognate death receptors DR4 or DR5, thereby being investigated as a potential agent for cancer therapy. Here, we applied fully human anti-human TRAIL receptor monoclonal antibodies (mAbs) to specifically target one of death receptors for TRAIL in human glioma cells, which could also reduce potential TRAIL-induced toxicity in humans. Twelve human glioma cell lines treated with several fully human anti-human TRAIL receptor mAbs were sensitive to only anti-DR5 mAbs, whereas they were totally insensitive to anti-DR4 mAb. Treatment with anti-DR5 mAbs exerted rapid cytotoxicity and lead to apoptosis induction. The cellular sensitivity was closely associated with cell-surface expression of DR5. Expression of c-FLIPL, Akt, and Cyclin D1 significantly correlated with sensitivity to anti-DR5 mAbs. Primary cultures of glioma cells were also relatively resistant to anti-DR5 mAbs, exhibiting both lower DR5 and higher c-FLIPL expression. Downregulation of c-FLIPL expression resulted in the sensitization of human glioma cells to anti-DR5 mAbs, whereas overexpression of c-FLIPL conferred resistance to anti-DR5 mAb. Treatment of tumor-burden nude mice with the direct agonist anti-DR5 mAb KMTR2 significantly suppressed growth of subcutaneous glioma xenografts leading to complete regression. Similarly, treatment of nude mice bearing intracerebral glioma xenografts with KMTR2 significantly elongated lifespan without tumor recurrence. These results suggest that DR5 is the predominant TRAIL receptor mediating apoptotic signals in human glioma cells, and sensitivity to anti-DR5 mAbs was determined at least in part by the expression level of c-FLIPL and Akt. Specific targeting of death receptor pathway through DR5 using fully human mAbs might provide a novel therapeutic strategy for intractable malignant gliomas. PMID:20511188

  10. 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

  11. Pharmacokinetics and biodistribution of radiolabeled avidin, streptavidin and biotin

    International Nuclear Information System (INIS)

    Rosebrough, S.F.

    1993-01-01

    The extraordinarily high affinity of avidin and streptavidin for biotin may be exploited in a two-step approach for delivering radiolabeled biotin derivatives suitable for imaging and therapy to target-bound streptavidin or avidin conjugated monoclonal antibodies (MAbs). The in vivo pharmacokinetics and biodistribution of radiolabeled avidin, streptavidin (SA) and DTPA-biocytinamide (DTPA-biotin) were studied in the rabbit and dog. SA circulated in the blood similar to other 60 kDa proteins, avidin cleared immediately and DTPA-biotin exhibited plasma clearance by glomerular filtration. (author)

  12. Biodistribution of radiolabeled lymphocytes

    International Nuclear Information System (INIS)

    Fawwaz, R.A.; Oluwole, S.; Wang, T.S.; Kuromoto, N.; Iga, C.; Hardy, M.A.; Alderson, P.O.

    1985-01-01

    Factors that might affect the biodistribution and clinical utility of radiolabeled lymphocytes were evaluated in experimental animals. Indium-111 (In-111) labeled lymphocytes obtained from peripheral blood, lymph node, or spleen were found in significant amounts in the lymphoid tissues of Lewis rats as early as 3 hours after infusion. A progressive increase in nodal activity with concomitant fall of activity in other organs followed, indicating active recirculation of the lymphocytes. In vitro irradiation of the In-111 labeled lymphocytes resulted in no detectable lymphocyte recirculation and/or reduced localization in lymphoid tissue. Splenectomized animals and those sensitized to an organ allograft before cell infusion showed increased activity in their bone marrow. These results suggest that the source of the injected cells, cell irradiation dose level and host sensitization should be considered when radiolabeled lymphocytes are being prepared for use in clinical diagnosis and therapy

  13. 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

  14. Pharmacokinetics of internally labeled monoclonal antibodies as a gold standard: comparison of biodistribution of 75Se-, 111In-, and 125I-labeled monoclonal antibodies in osteogenic sarcoma xenografts in nude mice

    International Nuclear Information System (INIS)

    Koizumi, M.; Endo, K.; Watanabe, Y.; Saga, T.; Sakahara, H.; Konishi, J.; Yamamuro, T.; Toyama, S.

    1989-01-01

    In order to know the true biodistribution of anti-tumor monoclonal antibodies, three monoclonal antibodies (OST6, OST7, and OST15) against human osteosarcoma and control antibody were internally labeled with 75Se by incubating [75Se]methionine and hybridoma cells. 75Se-labeled monoclonal antibodies were evaluated both in vitro and in vivo using the human osteogenic sarcoma cell line KT005, and the results were compared with those of 125I- and 111In-labeled antibodies. 75Se-, 125I- and 111In-labeled monoclonal antibodies had identical binding activities to KT005 cells, and the immunoreactivity was in the decreasing order of OST6, OST7, and OST15. On the contrary, in vivo tumor uptake (% injected dose/g) of 75Se- and 125I-labeled antibodies assessed using nude mice bearing human osteosarcoma KT005 was in the order of OST7, OST6, and OST15. In the case of 111In, the order was OST6, OST7, and OST15. High liver uptake was similarly seen with 75Se- and 111In-labeled antibodies, whereas 125I-labeled antibodies showed the lowest tumor and liver uptake. These data indicate that tumor targeting of antibody conjugates are not always predictable from cell binding studies due to the difference of blood clearance of labeled antibodies. Furthermore, biodistribution of both 111In- and 125I-labeled antibodies are not identical with internally labeled antibody. Admitting that internally labeled antibody is a ''gold standard'' of biodistribution of monoclonal antibody, high liver uptake of 111In-radiolabeled antibodies may be inherent to antibodies. Little, if any, increase in tumor-to-normal tissue ratios of antibody conjugates will be expected compared to those of 111In-labeled antibodies if stably coupled conjugates are administered i.v

  15. 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

  16. Radiolabelled antibodies in imaging

    International Nuclear Information System (INIS)

    Khaw, B.A.; Haber, E.

    1982-01-01

    Recent technological advances make it possible to produce pure (monoclonal) antibodies in unlimited quantities without the need for continuous immunization of animals and to label these antibodies with a variety of radionuclides which can be traced by single-photon computed tomography. An outline review of the state of the art is presented, with particular reference to the imaging of myocardial infarcts and to tumour imaging studies using labelled monoclonal antibodies (sup(99m)Tc and 125 I). Lengthy bibliography. (U.K.)

  17. 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.)

  18. Blood cells radiolabelling achievements, challanges, and prospects

    International Nuclear Information System (INIS)

    Weininger, Jolie; Trumper, Jacob

    1987-01-01

    A study in performed about the different ways of blood cells radiolabelling. The labelling of red blood cells (RBCs), compared with that of other blood cells, is facilitated by several factors such as a) RBCs are the most abundant of all cellular blood elements, b) they are relatively easy to separate and manipulate in vitro, c) in vitro they are less dependent on energy and nutricional requirements, d) they are easy to label due to the presence of a variety of cellular transport mechanism. 99m Tc was reconized and became as the ideal radioisotope for nuclear medicine imaging. After considerations about RBCs radiolabelling, it is presented a new in vitro technique based on the BNL kit, developed by Srivastava and co-workers. The Sorep optimized one-vial labelling method for 2 ml whole blood. In vivo and in vivo/in vitro labelling are presented too, the last method seems to combine the superior binding efficiency of in vitro labelling with the convenience of in vitro labelling. Lipophilic chelates of 111 In with oxine, acetylacetone, tropolone and mercaptopyridine N-oxide have been used successfully for labelling platelets and leukocytes. A very promising aproach is the labelling of cells with monoclonal antibodies and the developing optimized methods for in vitro labelling with various radionuclides such as 123 I, 125 I, 131 I, 111 I and 99m Tc. The advantages of the antibody technique over conventional cell labelling are shown. (M.E.L.) [es

  19. Radiolabeled antibodies in cancer. Oncology Overview

    International Nuclear Information System (INIS)

    1984-11-01

    Oncology Overviews are a service of the International Cancer Research Data Bank (ICRDB) Program of the National Cancer Institute, intended to facilitate and promote the exchange of information between cancer scientists by keeping them aware of literature related to their research being published by other laboratories through the world. Each Oncology Overview represents a survey of the literature associated with a selected area of cancer research. It contains abstracts of articles which have been selected and organized by researchers associated with the field. Contents: Radiolabeled antibodies--labeling and imaging techniques; Radiolabeled antibodies--carcinoembryonic antigen; Radiolabeled antibodies--alpha-fetoprotein; Radiolabeled antibodies--human chorionic gonadotropin; Radiolabeled antibodies--ferritin; Radiolabeled antibodies--imaging of colorectal tumors; Radiolabeled antibodies--imaging of malignant melanoma; Radiolabeled antibodies--imaging of urogenital tumors; Radiolabeled antibodies--imaging of thyroid tumors; Radiolabeled antibodies--other clinical studies; Radiolabeled antibodies--selected preclinical studies; Radiolabeled antibodies--reviews

  20. Radiolabelling for immunoassay

    International Nuclear Information System (INIS)

    Chapman, R.S.

    1998-01-01

    Since the early 1960s labelled compounds employed in immunoassay techniques, both radioimmunoassay and immunoradiometric assay, have involved radioisotopes typically 3 H (tritium) and 125 Iodine. With the advent of increasingly stringent governmental regulations regarding usage and disposal of radioisotopes and the impetus of research towards improved immunoassay sensitivity following the discovery of monoclonal antibodies and their application to excess reagent immunometric assay methodology, radioisotopic labels are gradually being replaced by non-isotopic labels: enzyme, fluorescence and chemiluminescence

  1. Radiolabeled derivatives of folic acid

    International Nuclear Information System (INIS)

    1980-01-01

    Derivatives of folic acid are described, in which the α-carboxyl group is substituted with an amino compound having an aromatic or heterocyclic ring substituent which is capable of being radiolabelled. Particularly mentioned as a radiolabel is 125 I. (author)

  2. 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

  3. Experimental radioimmunotherapy of a xenografted human glioma using [sup 131]I-labeled monoclonal antibody to epidermal growth factor receptor

    Energy Technology Data Exchange (ETDEWEB)

    Takahashi, Hiroshi; Nakazawa, Shozo [Nippon Medical School, Tokyo (Japan); Herlyn, D

    1993-09-01

    [sup 131]I-labeled F (ab')[sub 2] fragments of murine monoclonal antibodies (MAb) 425 specific to the epidermal growth factor receptor expressed on human gliomas were used in experimental human malignant glioma immunotherapy. Two injections of 150 [mu]Ci [sup 131]I-labeled 425 F(ab')[sub 2] achieved growth inhibition of U-87MG human malignant glioma xenografts in nude mice. This radiolabeled specific MAb F(ab')[sub 2] was significantly superior to radiolabeled fragments of an anti-hepatitis virus control MAb A5C3 in influencing tumor growth. However, similar treatment of established human malignant glioma xenografts did not inhibit progressive tumor growth significantly. No clear tumor inhibition was produced by unlabeled MAb 425F(ab')[sub 2]. These studies suggest that [sup 131]I-labeled MAbs have a significant antitumor effect where unmodified antibody is ineffective. Multiple doses of antibody may achieve an increase in labeled MAb concentration in tumors. (author).

  4. In vivo VEGF imaging with radiolabeled bevacizumab in a human ovarian tumor xenograft

    NARCIS (Netherlands)

    Nagengast, Wouter B.; Hospers, Geke A.; Mulder, Nanno H.; de Jong, Johan R.; Hollema, Harry; Brouwers, Adrienne H.; van Dongen, Guns A.; Perk, Lars R.; Lub-de Hooge, Marjolijn N.

    Vascular endothelial growth factor (VEGF), released by tumor cells, is an important growth factor in tumor angiogenesis. The humanized monoclonal antibody bevacizumab blocks VEGF-induced tumor angiogenesis by binding, thereby neutralizing VEGF. Our aim was to develop radiolabeled bevacizumab for

  5. Towards tumour targeting with copper-radiolabelled macrocycle-antibody conjugates

    Energy Technology Data Exchange (ETDEWEB)

    Morphy, J.R.; Parker, David; Kataky, Ritu; Harrison, Alice; Walker, Carole; Eaton, M.A.W.; Millican, Andrew; Phipps, Alison

    1989-06-15

    Tetraaza-macrocycles covalently attached to a monoclonal antibody may be efficiently radiolabelled with /sup 64/Cu or /sup 67/Cu at pH4, minimising non-specific binding to the protein, giving a kinetically stable conjugate in vivo. (author).

  6. Final Progress Report: SPECT Assay of Radiolabeled Monoclonal Antibodies

    International Nuclear Information System (INIS)

    Jaszczak, Ronald J.

    2004-01-01

    During the past project period, we proposed to collaborate closely with DOE's Thomas Jefferson National Accelerator Facility (Jefferson Lab or JLab) to design a compact, ultra-high-resolution, high-sensitivity gamma camera for quantifying brain-tumor distributions of I-131. We also proposed to continue our on-going research in developing and evaluating pinhole collimation for quantitative ultra-high-resolution imaging of I-131-labeled MAbs. We have made excellent progress in accomplishing much of the research related to pinhole collimation. Many of the most significant results have been presented in peer-reviewed journal articles and conference proceedings. We have also made good progress in collaborating with JLab's Detector Group in developing a compact, ultra-high-resolution, gamma camera. A prototype I-131 imager was delivered to Duke on May 28, 2003. Our research results are summarized in the following sections. A. JLAB-DUKE DEDICATED BRAIN-TUMOR IMAGING SYSTEM A.1. Determination of Optimal Collimator Design During the current project period a prototype I-131 dedicated brain imager has been designed and built. Computer simulations and analysis of alternate designs were performed at Duke to determine an optimal collimator design. Collimator response was characterized by spatial resolution and sensitivity. Both geometric (non-penetrative) and penetrative sensitivities were considered in selecting an optimal collimator design. Based on these simulation results, two collimator designs were selected and built by external vendors. Initial imaging results were obtained using these collimators. B. INITIAL DEVELOPMENT OF SPECT RECONSTRUCTION SOFTWARE FOR JLAB-DUKE CAMERA B.1. Modeling Thick Septa and Collimator Holes: Geometrical-Phantom Study A geometrical phantom was designed to illuminate spatial resolution effects. The phantom includes a uniformly attenuating medium that consists of all voxels within an elliptical cylinder that is centered on the axis of rotation, infinitely long, and with minor and major diameters of 15.0 and 22.0cm. Computer-simulated projections of the phantom were created. We observed that thick septa create a periodic and strong variation in sensitivity across the surface of the gamma camera, as evident in these projections. C. PINHOLE POINT-RESPONSE FUNCTION (PRF) AND ROOT-MEAN-SQUARE (RMS) NOISE During the previous project period, we developed an accurate analytic expression to determine the sensitivity of pinhole collimation that included the effects of penetration. During the current project period, we have developed an accurate model of the point-response function (PRF) of pinhole collimators. D. COMPLETE SAMPLING: THEORETICAL AND COMPUTATIONAL DEVELOPMENTS During this project period, we have investigated the complete-sampling conditions for orbits of pinhole collimators and have published these data. We have made progress in both complete-sampling theory and also in computational methods. Pinhole collimation has similar complete sampling properties to cone-beam collimation. Complete sampling of an object cannot be obtained from the circular rotation of the aperture about the object. We have investigated helical-orbit pinhole SPECT scans as a method of obtaining completely sampled data. Helical orbits were evaluated because they offer the potential of a small ROR for high sensitivity and resolution combined with complete sampling. We compared reconstructions from simulated circular-orbit and simulated helical-orbit projection data and observed a marked improvement in image quality when helical-orbits are used for the data acquisition. E. PINHOLE CALIBRATION STUDIES We have begun a study of the effects of mechanical and electronic shifts on reconstruction that suggests that even very small shifts (a fraction of a millimeter) can introduce substantial artifacts in the reconstruction. We have acquired experimental calibration data using point sources. We fitted the centroids simultaneously to the expected mechanical and electronic components determined by an analytically derived equation. The mechanical and electronic shifts were determined using a maximum likelihood fit. The data show good agreement with expectation. The axial-shift results for the pinhole collimator demonstrated an approximately sinusoidal characteristic; that is, it is angularly dependent. To test the effect mechanical shift on reconstructed image quality, experimental data were acquired using a micro cold-rod phantom. The SPECT image that used the correct estimated mechanical shift was markedly improved compared with the other uncorrected SPECT images

  7. Dosimetry of radiolabeled monoclonal antibodies used for therapy

    International Nuclear Information System (INIS)

    Myers, M.J.; Hooker, G.R.; Epenetos, A.A.

    1986-01-01

    The present state of radiotherapy using labeled antibodies is reviewed. From the point of view of dosimetry, antibody therapy does not seem to have reached a stable and practicable enough state to provide an input to any but rather tentative dosimetry models. These, therefore, should not be taken too far until the problems of antibody targeting have been more fully developed. Some of the instrumental techniques for acquiring dosimetric data under clinical conditions are discussed as are some of the techniques of therapy in use today. 8 references, 3 figures

  8. Radiolabeling of biological vectors by poly-aza-macrocyclic complexes

    International Nuclear Information System (INIS)

    Moreau, M.

    2012-01-01

    This work conducted at the 'Institut de Chimie Moleculaire de l'Universite de Bourgogne' carries at first on the synthesis of bifunctional chelating agents suitable for the chelation of trivalent radio-metals, including indium-111. The greater part of this work was then dedicated to the grafting of a DOTA derivative bifunctional chelating agent on different antibodies or fragments of monoclonal antibodies: trastuzumab (anti-HER2 treatment of breast cancer), cetuximab (anti EGFR, treatment of many cancers, including colorectal cancer) and abciximab (antiplatelet). Particular attention was paid to the characterization of various immuno-conjugates. The critical step of this thesis consisted in the indium-111 radiolabeling of two previously prepared immuno-conjugates: trastuzumab and cetuximab. These steps of radiolabelling allowed us to determine the immunoreactive fraction and affinity of each radiotracer. Thus, we were able to study the in vivo biodistribution of the radiotracers in tumour-bearing mice by SPECT-CT. We also developed an original method for the labeling of a Fab antibody fragment in order to monitor the biodistribution of the antiplatelet agent (abciximab). Finally, we also validated the concept of multimodal imaging through grafting and radiolabeling of a bimodal agent for optical and SPECT imaging on bacterial lipopolysaccharide. Thanks to this work, we gained an expertise in antibodies radiolabeling. The results obtained allow to consider the labeling of antibodies or other biomolecules, and the use of other radionuclides for PET imaging and radioimmunotherapy. (author)

  9. Methods to obtain radiolabelled monocrotaline

    International Nuclear Information System (INIS)

    Lame, M.W.; Morin, D.; Wilson, D.W.; Segall, H.J.

    1996-01-01

    Crotalaria spectabilis, a plant found in many areas of the world is associated with the pyrrolizidine alkaloid monocrotaline. Monocrotaline when injected subcutaneously in Sprague Dawley rats has been utilized for years to create a condition known to mimic pulmonary hypertension in humans. We attempted to determine the optimum conditions for the biosynthesis of radiolabelled monocrotaline. Our work describes the plant growth conditions and the time periods associated with the production of radiolabelled monocrotaline. In addition, the incorporation of 14 CO 2 or [2,3- 3 H]-putrescine dihydrochloride and the specific activity plus the amount(s) of recovered radiolabelled monocrotaline are discussed. We conclude that the most efficient and cost effective method for the biosynthesis of radiolabelled monocrotaline is still the utilization of 14 CO 2 . (author)

  10. Methods to obtain radiolabelled monocrotaline

    Energy Technology Data Exchange (ETDEWEB)

    Lame, M.W.; Morin, D.; Wilson, D.W.; Segall, H.J. [University of California, Davis, CA (United States)

    1996-12-01

    Crotalaria spectabilis, a plant found in many areas of the world is associated with the pyrrolizidine alkaloid monocrotaline. Monocrotaline when injected subcutaneously in Sprague Dawley rats has been utilized for years to create a condition known to mimic pulmonary hypertension in humans. We attempted to determine the optimum conditions for the biosynthesis of radiolabelled monocrotaline. Our work describes the plant growth conditions and the time periods associated with the production of radiolabelled monocrotaline. In addition, the incorporation of {sup 14}CO{sub 2} or [2,3-{sup 3}H]-putrescine dihydrochloride and the specific activity plus the amount(s) of recovered radiolabelled monocrotaline are discussed. We conclude that the most efficient and cost effective method for the biosynthesis of radiolabelled monocrotaline is still the utilization of {sup 14}CO{sub 2}. (author).

  11. Radiolabelling of cholera toxin

    Energy Technology Data Exchange (ETDEWEB)

    Santos, R.G.; Neves, Nicoli M.J. [Centro de Desenvolvimento da Tecnologia Nuclear (CDTN), Belo Horizonte, MG (Brazil); Abdalla, L.F.; Brandao, R.L.; Etchehebehere, L. [Ouro Preto Univ., MG (Brazil). Escola de Farmacia. Lab. de Fisiologia e Bioquimica de Microorganismos; Lima, M.E. de [Minas Gerais Univ., Belo Horizonte, MG (Brazil). Inst. de Ciencias Biologicas. Dept. de Bioquimica e Imunologia; Nicoli, J.R. [Minas Gerais Univ., Belo Horizonte, MG (Brazil). Inst. de Ciencias Biologicas. Dept. de Microbiologia

    1999-11-01

    Binding of cholera toxin to ganglioside receptors of enterocyte microvilli catalyzes the activation of adenylate cyclase causing a rise in cAMP which final result is a copious diarrhea. Saccharomyces boulardii, a nonpathogenic yeast has been used to prevent diarrhea. Although the antidiarrheic properties of S. boulardii are widely recognized, this yeast has been used on empirical basis, and the mechanism of this protective effect is unknown. The addition of cholera toxin to S. boulardii induces the raising of cAMP that triggers the activation of neutral trehalase. This suggests that toxin specifically binding to cells, is internalized and active the protein phosphorylation cascade. Our objective is labeling the cholera toxin to verify the presence of binding sites on yeast cell surfaces for the cholera toxin. Cholera toxin was radiolabelled with Na {sup 125} I by a chloramine-T method modified from Cuatrecasas and Griffiths et alii. The {sup 125} I-Cholera toxin showed a specific radioactivity at about 1000 cpm/fmol toxin. Biological activity of labeled cholera toxin measured by trehalase activation was similar to the native toxin. (author) 5 refs., 3 figs.; e-mail: nevesmj at urano.cdtn.br

  12. Radiolabelling of cholera toxin

    International Nuclear Information System (INIS)

    Santos, R.G.; Neves, Nicoli M.J.; Abdalla, L.F.; Brandao, R.L.; Etchehebehere, L.; Lima, M.E. de; Nicoli, J.R.

    1999-01-01

    Binding of cholera toxin to ganglioside receptors of enterocyte microvilli catalyzes the activation of adenylate cyclase causing a rise in cAMP which final result is a copious diarrhea. Saccharomyces boulardii, a nonpathogenic yeast has been used to prevent diarrhea. Although the antidiarrheic properties of S. boulardii are widely recognized, this yeast has been used on empirical basis, and the mechanism of this protective effect is unknown. The addition of cholera toxin to S. boulardii induces the raising of cAMP that triggers the activation of neutral trehalase. This suggests that toxin specifically binding to cells, is internalized and active the protein phosphorylation cascade. Our objective is labeling the cholera toxin to verify the presence of binding sites on yeast cell surfaces for the cholera toxin. Cholera toxin was radiolabelled with Na 125 I by a chloramine-T method modified from Cuatrecasas and Griffiths et alii. The 125 I-Cholera toxin showed a specific radioactivity at about 1000 cpm/fmol toxin. Biological activity of labeled cholera toxin measured by trehalase activation was similar to the native toxin. (author)

  13. Radiolabelled antibody imaging

    International Nuclear Information System (INIS)

    Perkins, A.C.

    1986-01-01

    A steadily growing number of tumor-associated antigens are used to raise antibodies used for the detection of human tumors by external imaging, a technique termed immunoscintigraphy. The majority of these clinical antibody studies are performed using Iodine-131, which is cheap, readily available and easily attached to protein. It has the disadvantage of having a high energy gamma emission (365 keV) which is poorly detected by modern cameras, so that increasing use is now being made of more appropriate labels with lower energies for imaging, such as Iodine-123, Indium-111 and Technetium-99m. A number of research centres in the United Kingdom are currently involved in the production of tumor-associated monoclonal antibodies, only a small number of which are finally selected for diagnostic use. These developments represent a major area of advancement in Nuclear Medicine and when used for imaging are capable of providing diagnostic information complimentary to other diagnostic techniques

  14. Imaging of colorectal carcinoma with radiolabeled antibodies.

    Science.gov (United States)

    Goldenberg, D M; Goldenberg, H; Sharkey, R M; Lee, R E; Higgenbotham-Ford, E; Horowitz, J A; Hall, T C; Pinsky, C M; Hansen, H J

    1989-10-01

    Colorectal cancer has been the tumor type most frequently studied with radiolabeled antibodies. Among the various antibodies, a majority of patients with colorectal cancer have received xenogeneic polyclonal or monoclonal antibodies against carcino-embryonic antigen. This review summarizes the current status of colorectal cancer imaging with radiolabeled antibodies, ie, radioimmunodetection (RAID), and examines the published studies involving carcinoembryonic antigen (CEA) antibodies and 17-1A, 19-9, and B72.3, and other monoclonal antibodies. In order to better address the issue of the current and future clinical usefulness of this emerging technology, particular attention is given to the protocols, methods, and results of the published studies. Despite differences in study parameters, antibodies and forms, labels, administration routes and doses, and scanning instruments and methods, it has been found that (1) almost no adverse reactions have been evident; (2) antibody fragments are preferred over whole immunoglobulin G reagents because they achieve higher tumor-to-background ratios earlier, thus reducing or precluding the need for dual-isotope subtraction methods or long delays before imaging; (3) use of antibody fragments, including the monovalent Fab' form, permits imaging with short-lived radionuclides of excellent photon properties, such as 123I and 99mTc; (4) circulating antigens against which the imaging antibody is directed can complex with the injected antibody, but such complexes have not prevented successful RAID; (5) patients with high serum titers of the appropriate antigen target usually have higher rates of positive RAID; (6) patients who are seronegative for the tumor antigen being studied can have positive RAID findings, which can represent the detection of occult lesions; (7) single photon emission computed tomography appears to provide better image resolution than planar scanning; (8) regardless of the sensitivity reported in any particular

  15. Radiolabelling of antibodies with indium: Use of diethylenetriaminepentaacetic acid (DTPA) as chelating agent

    International Nuclear Information System (INIS)

    Loetscher, H.

    1986-01-01

    /sup 111/In/sup 3+/ was used to radiolabel the F(ab')/sub 2/ fragment of a monoclonal antibody (b-12) raised against a surface antigen of a mammalian breast tumor cell line (5). The in vivo distribution of the radiolabel was analyzed in mice bearing a transplant of fixed tumor cells in the left thigh. The results demonstrate that DTPA can be efficiently coupled to a tumor specific F(ab')/sub 2/ fragment and loaded with /sup 111/In/sup 3+/ yielding a stable, highly labelled complex

  16. Radiolabeling parameters of {sup 177}Lu-DOTA-RITUXIMAB

    Energy Technology Data Exchange (ETDEWEB)

    Massicano, Adriana V.F.; Alcarde, Lais F.; Oliveira, Ricardo S.; Mengatti, Jair; Araujo, Elaine B. de, E-mail: adriana.avfernandes@gmail.com [Instituto de Pesquisas Energeticas e Nucleares (IPEN/CNEN-SP), Sao Paulo, SP (Brazil)

    2013-07-01

    Cancer treatment using radioimmunotherapy (RIT) has been the focus of much research in the last two decades. In RIT, a radioisotope is coupled to a monoclonal antibody (mAb) to form a tumor-specific target agent to improve the cytocidal effect of the mAbs. RIT allows the systemic delivery of radiation to disease target by mAbs while sparing normal tissues. Rituximab® (Mabthera - Roche) is a chimeric mouse-human monoclonal antibody; it selectively binds with high affinity to the CD20 antigen, a hydrophobic transmembrane protein, which is expressed on B-lymphocytes and in more than 90% of B cell non-Hodgkin's lymphomas (NHL). The conjugation and radiolabeling process involve special conditions of pH and temperature, long processes of manipulation and mixing. All this process can damage the antibody structure and compromise its clinical application. Therefore, these parameters must be largely studied. The aim of this work was to evaluate the best radiolabeling conditions of DOTA-rituximab. Briefly, 10 mg of antibody previously purified by ultrafiltration device was conjugated with DOTA-NHS-ester (Macrocyclics) in 50 fold molar excess. The reaction was conducted for 1 hour in phosphate buffer pH 8.0 and gently mixing at room temperature, remaining for 24 hours under refrigeration. The immunoconjugated was purified by size exclusion column and ultrafiltration device. The radiolabeled parameters studied were: immunoconjugated mass, activity of {sup 177}LuCl{sub 3}, reaction time, temperature and pH. The radiochemical purity of the preparations was determined using analysis by thin layer chromatography (TLC-SG plates). The best studied condition presented radiochemical purity above 95% and the integrity of antibody was preserved. (author)

  17. Radiolabeling parameters of 177Lu-DOTA-RITUXIMAB

    International Nuclear Information System (INIS)

    Massicano, Adriana V.F.; Alcarde, Lais F.; Oliveira, Ricardo S.; Mengatti, Jair; Araujo, Elaine B. de

    2013-01-01

    Cancer treatment using radioimmunotherapy (RIT) has been the focus of much research in the last two decades. In RIT, a radioisotope is coupled to a monoclonal antibody (mAb) to form a tumor-specific target agent to improve the cytocidal effect of the mAbs. RIT allows the systemic delivery of radiation to disease target by mAbs while sparing normal tissues. Rituximab® (Mabthera - Roche) is a chimeric mouse-human monoclonal antibody; it selectively binds with high affinity to the CD20 antigen, a hydrophobic transmembrane protein, which is expressed on B-lymphocytes and in more than 90% of B cell non-Hodgkin's lymphomas (NHL). The conjugation and radiolabeling process involve special conditions of pH and temperature, long processes of manipulation and mixing. All this process can damage the antibody structure and compromise its clinical application. Therefore, these parameters must be largely studied. The aim of this work was to evaluate the best radiolabeling conditions of DOTA-rituximab. Briefly, 10 mg of antibody previously purified by ultrafiltration device was conjugated with DOTA-NHS-ester (Macrocyclics) in 50 fold molar excess. The reaction was conducted for 1 hour in phosphate buffer pH 8.0 and gently mixing at room temperature, remaining for 24 hours under refrigeration. The immunoconjugated was purified by size exclusion column and ultrafiltration device. The radiolabeled parameters studied were: immunoconjugated mass, activity of 177 LuCl 3 , reaction time, temperature and pH. The radiochemical purity of the preparations was determined using analysis by thin layer chromatography (TLC-SG plates). The best studied condition presented radiochemical purity above 95% and the integrity of antibody was preserved. (author)

  18. Correlating labeling chemistry and in-vitro test results with the biological behavior of radiolabeled proteins

    International Nuclear Information System (INIS)

    Srivastava, S.C.; Meinken, G.E.

    1985-01-01

    Monoclonal antibodies possess enormous potential for delivery of therapeutic amounts of radionuclides to target antigens in vivo, in particular for tumor imaging and therapy. Translation of this concept into practice has encountered numerous problems. Specifically whereas general protein radiolabeling methods are applicable to antibodies, immunological properties of the antibodies are often compromised resulting in reduced in-vivo specificity for the target antigens. The bifunctional chelating agent approach shows the most promise, however, development of other agents will be necessary for widespread usefulness of this technique. The effects of labeling chemistry on the in-vivo behavior of several monoclonal antibodies are described. 30 refs., 4 figs., 10 tabs

  19. 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

  20. Radiolabelled peptides for oncological diagnosis

    Energy Technology Data Exchange (ETDEWEB)

    Laverman, Peter; Boerman, Otto C.; Oyen, Wim J.G. [Radboud University Nijmegen Medical Centre, Department of Nuclear Medicine, Nijmegen (Netherlands); Sosabowski, Jane K. [Queen Mary University of London, Centre for Molecular Oncology, Barts Cancer Institute, London (United Kingdom)

    2012-02-15

    Radiolabelled receptor-binding peptides targeting receptors (over)expressed on tumour cells are widely under investigation for tumour diagnosis and therapy. The concept of using radiolabelled receptor-binding peptides to target receptor-expressing tissues in vivo has stimulated a large body of research in nuclear medicine. The {sup 111}In-labelled somatostatin analogue octreotide (OctreoScan trademark) is the most successful radiopeptide for tumour imaging, and was the first to be approved for diagnostic use. Based on the success of these studies, other receptor-targeting peptides such as cholecystokinin/gastrin analogues, glucagon-like peptide-1, bombesin (BN), chemokine receptor CXCR4 targeting peptides, and RGD peptides are currently under development or undergoing clinical trials. In this review, we discuss some of these peptides and their analogues, with regard to their potential for radionuclide imaging of tumours. (orig.)

  1. 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)

  2. 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.

  3. Radiopharmaceutical development of radiolabelled peptides

    Energy Technology Data Exchange (ETDEWEB)

    Fani, Melpomeni; Maecke, Helmut R. [University Hospital Freiburg, Department of Nuclear Medicine, Freiburg (Germany)

    2012-02-15

    Receptor targeting with radiolabelled peptides has become very important in nuclear medicine and oncology in the past few years. The overexpression of many peptide receptors in numerous cancers, compared to their relatively low density in physiological organs, represents the molecular basis for in vivo imaging and targeted radionuclide therapy with radiolabelled peptide-based probes. The prototypes are analogs of somatostatin which are routinely used in the clinic. More recent developments include somatostatin analogs with a broader receptor subtype profile or with antagonistic properties. Many other peptide families such as bombesin, cholecystokinin/gastrin, glucagon-like peptide-1 (GLP-1)/exendin, arginine-glycine-aspartic acid (RGD) etc. have been explored during the last few years and quite a number of potential radiolabelled probes have been derived from them. On the other hand, a variety of strategies and optimized protocols for efficient labelling of peptides with clinically relevant radionuclides such as {sup 99m}Tc, M{sup 3+} radiometals ({sup 111}In, {sup 86/90}Y, {sup 177}Lu, {sup 67/68}Ga), {sup 64/67}Cu, {sup 18}F or radioisotopes of iodine have been developed. The labelling approaches include direct labelling, the use of bifunctional chelators or prosthetic groups. The choice of the labelling approach is driven by the nature and the chemical properties of the radionuclide. Additionally, chemical strategies, including modification of the amino acid sequence and introduction of linkers/spacers with different characteristics, have been explored for the improvement of the overall performance of the radiopeptides, e.g. metabolic stability and pharmacokinetics. Herein, we discuss the development of peptides as radiopharmaceuticals starting from the choice of the labelling method and the conditions to the design and optimization of the peptide probe, as well as some recent developments, focusing on a selected list of peptide families, including somatostatin

  4. 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

  5. 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)

  6. Extraction, radiolabeling and in vivo biological evaluation of {sup 131}I labeled egonol glycosides extract

    Energy Technology Data Exchange (ETDEWEB)

    Akguel, Yurdanur; Pazar, Erdinc [Ege Univ., Izmir (Turkey). Chemistry Dept.; Yilmaz, Habibe; Sanlier, Senay Hamarat [Ege Univ., Izmir (Turkey). Biochemistry Dept.; Lambrecht, Fatma Yurt [Ege Univ., Izmir (Turkey). Dept. of Nuclear Applications; Yilmaz, Osman [Dokuz Eyluel Univ., Izmir (Turkey). Dept. of Lab. Animal Science

    2015-09-01

    Crude extract of S. officinalis L. was found to have suspending agent, hemolytic, antitumor, antioxidant and antimicrobial activities. Its major components benzofurans and benzofuran glycosides have antifungal, anticancer, antibacterial and anticomplement activities and display acetylcholinesterase-cyclooxygenase inhibitory and cytotoxic properties. Recently, it has been reported that egonolgentiobioside is a valuable target for structural modification and warrants further investigation for its potential as a novel pharmaceutical tool for the prevention of estrogen deficiency induced diseases. The aim of the current study is to perform in vivo biological evaluation of a glycosides extract, which was isolated from the fruits endocarp of Styrax officinalis L, identified as egonolgentiobioside and homoegonolgentiobioside and labeled with {sup 131}I. The radiolabeled glycosides extract was labeled with {sup 131}I with high yield. The labeled obtained radiolabeled compound was found to be quite stable and lipophilic. In order to determine its tissue distribution, an in vivo study was performed using healthy female Albino Wistar rats injected by {sup 131}I-glycosides. The biodistribution results showed that clearance of the radiolabeled compound is through the hepatobiliary pathway. The experimental study indicated that the radiolabeled glycosides extract accumulated in the large intestine. Therefore, the potential of {sup 131}I-glycosides might be evaluated in colon cancer cell lines and this might be a promising of tumor-imaging agent.

  7. Cancer imaging with radiolabeled antibodies

    International Nuclear Information System (INIS)

    Goldenberg, D.M.

    1990-01-01

    This book presents a perspective of the use of antibodies to target diagnostic isotopes to tumors. Antibodies with reasonable specificity can be developed against almost any substance. If selective targeting to cancer cells can be achieved, the prospects for a selective therapy are equally intriguing. But the development of cancer detection, or imaging, with radiolabeled antibodies has depended upon advances in a number of different areas, including cancer immunology and immunochemistry for identifying suitable antigen targets and antibodies to these targets, tumor biology for model systems, radiochemistry for he attachment of radionuclides to antibodies, molecular biology for reengineering the antibodies for safer and more effective use in humans, and nuclear medicine for providing the best imaging protocols and instrumentation to detect minute amounts of elevated radioactivity against a background of considerable noise. Accordingly, this book has been organized to address the advances that are being made in many of these areas

  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. Comparison of the chemical behaviour of humanized ACMS VS. Human IGG radiolabeled with 99mTc

    International Nuclear Information System (INIS)

    Rivero Santamaria, Alejandro; Zayas Crespo, Francisco; Mesa Duennas, Niurka; Castillo Vitloch, Adolfo J.

    2003-01-01

    The purpose of this work is to compare the chemical behaviour of humanized AcMs vs. human IgG radiolabeled with 99 mTc. to this end, 3 immunoglobulins were analyzed, the IgG (human), the humanized monoclonal antibody R3 (Acm-R3h) and the humanized monoclonal antibody T1. The results obtained reveal slight differences as regards the behaviour of theses immunoglobulins before the labelling with 99T c, which shows differences in the chemical behaviour of these proteins. Although in theory the modifications that are made to the AcMs in order to humanize them must not affect their chemical behaviour, the obtained data indicate that the conditions for their radiolabelling should not be extrapolated from other proteins; on the contrary, particular procedures should be elaborated for each AcM-h

  10. Bystander responses in three-dimensional cultures containing radiolabelled and unlabelled human cells

    International Nuclear Information System (INIS)

    Pinto, M.; Azzam, E. I.; Howell, R. W.

    2006-01-01

    Research on the radiation-induced bystander effect has been carried out mainly in 2-D tissue culture systems. This study uses a 3-D model, wherein apparently normal human diploid fibroblasts (AG1522) are grown in a carbon scaffold, to investigate the induction of a G 1 checkpoint in bystander cells present alongside radiolabelled cells. Cultures were simultaneously pulse-labelled with 3 H-deoxycytidine ( 3 HdC) to selectively irradiate a minor fraction of cells, and bromodeoxyuridine (BrdU) to identify the radiolabelled cells. After thorough washing of cultures, iododeoxyuridine (IdU) was administered to detect proliferating bystander cells. The cultures were harvested at various times thereafter, and cells were reacted with two monoclonal antibodies specific to IdU/BrdU or BrdU, respectively, stained with propidium iodide, and subjected to multi-parameter flow cytometry. Cell-cycle progression was followed in radiolabelled cells (BrdU + ) that were chronically irradiated by low energy beta particles emitted by DNA-incorporated 3 H, and in unlabelled bystander cells (BrdU - ) by a flow cytometry based cumulative labelling index assay. As expected, radiolabelled cells were delayed, in a dose-dependent manner, in G 2 and subsequently G 1 . No delay occurred in progression of bystander cells through G 1 , when the labelled cells were irradiated at dose rates up to 0.32 Gy h -1 . (authors)

  11. Reactivity comparison of biological material after radiolabeling with avidin-biotin system

    International Nuclear Information System (INIS)

    Fan Wo; Qian Jianhua; Zhu Benxing

    2003-01-01

    To find a method for determining the immunoreactivity of monoclonal antibodies after radiolabeling avidin is unlabeled and labeled with Rodamine, 131 I and 188 Re, respectively. The affinities and half-desorbed amounts of biotin and four kinds of avidin are determined by the biotin columns plus non-labeled avidin (cold avidin). The affinities of biotin and avidin unlabeled and labeled with Rodamine, 188 Re and 131 I are decreased in turn. Their half-desorbed amounts from biotin are 21.9, 19.5, 25.7 and 47.9 μg of cold avidin. Two kinds of radiolabeled avidin have lower affinity with biotin than that of avidin unlabeled and labeled with Rodamine. There is a possibility to evaluate the reactivity of biological materials with different labeling methods by avidin-biotin system

  12. Advance of apoptosis imaging with radiolabeled annexin V in tumor research

    International Nuclear Information System (INIS)

    Huang Daijuan

    2003-01-01

    One of the most important reasons that cause tumor is decrease or complete absence of apoptosis of tumor cells. Conversely successful anti-tumor therapy is correlated with the introduction of apoptosis into tumor cells. Radiolabeled annexin V is used to image in vivo the phosphatidylserine (PS) that explode on the outer surface of cell membrane after apoptosis so that apoptosis can be detected on the early stage. This imaging method can be introduced into the research of tumor in order to help direct the choose of tumor therapy, inspect the effect and evaluate the prognosis

  13. Localization of tumors by radiolabelled antibodies

    International Nuclear Information System (INIS)

    Hansen, H.J.; Primus, F.J.

    1975-01-01

    A method of utilizing radiolabelled antibodies to carcinoembryonic antigens for determining the site of tumors which produce or are associated with carcinoembryonic antigen is disclosed. 3 claims, no drawings

  14. Radiolabeled peptides: experimental and clinical applications

    International Nuclear Information System (INIS)

    Thakur, M.L.; Pallela, V.R.

    1998-01-01

    Radiolabeled receptor specific biomolecules hold unlimited potential in nuclear medicine. During the past few years much attention has been drawn to the development radiolabeled peptides for a variety of diagnostic applications, as well as for therapy of malignant tumors. Although only one peptide, In-111-DTPA-(D)-Phe 1 -octreotide, is available commercially for oncologic imaging, many more have been examined in humans with hematological disorders, and the early results appear to be promising. Impetus generated by these results have prompted investigators to label peptides with such radionuclides as Tc-99m, I-123, F-18, Cu-64, and Y-90. This review is intended to highlight the qualities of peptides, summarize the clinical results, and address some important issues associated with radiolabeling of highly potent peptides. While doing so, various methods of radiolabeling have been described, and their strengths and weaknesses have also been discussed. (author)

  15. 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

  16. 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…

  17. Three-site sandwich radioimmunoassay with monoclonal antibodies for a sensitive determination of human alpha-fetoprotein

    International Nuclear Information System (INIS)

    Nomura, M.; Imai, M.; Takahashi, K.; Kumakura, T.; Tachibana, K.; Aoyagi, S.; Usuda, S.; Nakamura, T.; Miyakawa, Y.; Mayumi, M.

    1983-01-01

    Utilizing monoclonal antibodies against human alpha-fetoprotein, 3 distinct antigenic determinants were identified. These antigenic determinants, provisionally designated a, b and c, were arranged in such a manner that the binding of one determinant with the corresponding antibody did not inhibit, or only barely inhibited the binding of antibodies directed to the other 2 determinants. Monoclonal antibodies with 3 different specificities were, therefore, applied to develop a sandwich-type solid-phase radioimmunoassay of the antigen in which wells were coated with anti-a, and radiolabeled anti-b together with radiolabeled anti-c was employed to detect the bound antigen. The 3-site sandwich radioimmunoassay involving 3 different determinants gave a higher sensitivity than 2-site assays in which only anti-b or anti-c was employed as a radiolabeled reagent, because the radioactivity of the 2 labeled antibodies was added on the antigen bound to immobilized anti-a. (Auth.)

  18. 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

  19. 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

  20. A review: radiolabeled synthesis of pesticides

    International Nuclear Information System (INIS)

    Li Juying; Han Ailiang; Wang Haiyan; Wang Wei; Ye Qingfu

    2010-01-01

    Isotope tracer technique has been widely applied in studies of metabolism, mode action, fate and environmental behavior of pesticides. In such studies, the key point is to obtain suitable radiolabelled compounds. However, the radiotracers, especially the labelled pesticides which are novel compounds with complex structures and longer synthesis routes, are usually unavailable from domestic and /or foreign markets. Therefore, it is essential to explore the synthesis methods of radiolabelled pesticides, which are quite different from the conventional nonradiosynthesis, and are requested to obtain higher yield. This article is a review on current status of choosing the available radionuclide and labelled position, the main synthesis methods and problems in the process of preparing radiolabelled pesticides. (authors)

  1. Radiolabelled RGD peptides for imaging and therapy

    Energy Technology Data Exchange (ETDEWEB)

    Gaertner, F.C.; Schwaiger, M.; Beer, A.J. [Technische Universitaet Muenchen, Department of Nuclear Medicine, Klinikum rechts der Isar, Munich (Germany); Kessler, H. [Technische Universitaet Muenchen, Institute for Advanced Study and Center of Integrated Protein Science, Department of Chemistry, Garching (Germany); King Abdulaziz University, Chemistry Department, Faculty of Science, Jeddah (Saudi Arabia); Wester, H.-J. [Institute for Pharmaceutical Radiochemistry, Garching (Germany)

    2012-02-15

    Imaging of angiogenesis has become increasingly important with the rising use of targeted antiangiogenic therapies like bevacizumab (Avastin). Non-invasive assessment of angiogenic activity is in this respect interesting, e.g. for response assessment of such targeted antiangiogenic therapies. One promising approach of angiogenesis imaging is imaging of specific molecular markers of the angiogenic cascade like the integrin {alpha}{sub v}{beta}{sub 3}. For molecular imaging of integrin expression, the use of radiolabelled peptides is still the only approach that has been successfully translated into the clinic. In this review we will summarize the current data on imaging of {alpha}{sub v}{beta}{sub 3} expression using radiolabelled RGD peptides with a focus on tracers already in clinical use. A perspective will be presented on the future clinical use of radiolabelled RGD peptides including an outlook on potential applications for radionuclide therapy. (orig.)

  2. 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

  3. Composition and method for stabilizing radiolabelled compounds using thiocarbonylated diethylenetriamines

    International Nuclear Information System (INIS)

    Tzodikov, N.R.

    1984-01-01

    Radiolabelled compounds, such as amino acids, nucleosides, vitamins and drugs, are stabilised against radiolytic decomposition by adding a solution of a thiocarbonylated diethylenetriamine to a solution of the radiolabelled compound. (author)

  4. Synthesis of 14C-radiolabelled Tilmicosin

    International Nuclear Information System (INIS)

    Crouse, G.D.; Terando, N.H.

    1989-01-01

    Tilmicosin was radiolabelled with carbon-14 on the 3,5-dimethylpiperidinyl sidechain as a requirement for animal metabolism studies. A new radiosynthesis of 3,5-dimethyl-piperidine was developed for this purpose. Incorporation into the desmycosin nucleus was accomplished by a reductive amination reaction. (author)

  5. 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.)

  6. Microfluidic radiolabeling of biomolecules with PET radiometals

    International Nuclear Information System (INIS)

    Zeng Dexing; Desai, Amit V.; Ranganathan, David; Wheeler, Tobias D.; Kenis, Paul J.A.; Reichert, David E.

    2013-01-01

    Introduction: A robust, versatile and compact microreactor has been designed, fabricated and tested for the labeling of bifunctional chelate conjugated biomolecules (BFC-BM) with PET radiometals. Methods: The developed microreactor was used to radiolabel a chelate, either 1,4,7,10-Tetraazacyclododecane-1,4,7,10-tetraacetic acid (DOTA) or 1,4,7-triazacyclononane-1,4,7-triacetic acid (NOTA) that had been conjugated to cyclo(Arg-Gly-Asp-DPhe-Lys) peptide, with both 64 Cu and 68 Ga respectively. The microreactor radiolabeling conditions were optimized by varying temperature, concentration and residence time. Results: Direct comparisons between the microreactor approach and conventional methods showed improved labeling yields and increased reproducibility with the microreactor under identical labeling conditions, due to enhanced mass and heat transfer at the microscale. More importantly, over 90% radiolabeling yields (incorporation of radiometal) were achieved with a 1:1 stoichiometry of bifunctional chelate biomolecule conjugate (BFC-BM) to radiometal in the microreactor, which potentially obviates extensive chromatographic purification that is typically required to remove the large excess of unlabeled biomolecule in radioligands prepared using conventional methods. Moreover, higher yields for radiolabeling of DOTA-functionalized BSA protein (Bovine Serum Albumin) were observed with 64 Cu/ 68 Ga using the microreactor, which demonstrates the ability to label both small and large molecules. Conclusions: A robust, reliable, compact microreactor capable of chelating radiometals with common chelates has been developed and validated. Based on our radiolabeling results, the reported microfluidic approach overall outperforms conventional radiosynthetic methods, and is a promising technology for the radiometal labeling of commonly utilized BFC-BM in aqueous solutions.

  7. Microfluidic radiolabeling of biomolecules with PET radiometals.

    Science.gov (United States)

    Zeng, Dexing; Desai, Amit V; Ranganathan, David; Wheeler, Tobias D; Kenis, Paul J A; Reichert, David E

    2013-01-01

    A robust, versatile and compact microreactor has been designed, fabricated and tested for the labeling of bifunctional chelate conjugated biomolecules (BFC-BM) with PET radiometals. The developed microreactor was used to radiolabel a chelate, either 1,4,7,10-tetraazacyclododecane-1,4,7,10-tetraacetic acid (DOTA) or 1,4,7-triazacyclononane-1,4,7-triacetic acid (NOTA) that had been conjugated to cyclo(Arg-Gly-Asp-DPhe-Lys) peptide, with both ⁶⁴Cu and ⁶⁸Ga respectively. The microreactor radiolabeling conditions were optimized by varying temperature, concentration and residence time. Direct comparisons between the microreactor approach and conventional methods showed improved labeling yields and increased reproducibility with the microreactor under identical labeling conditions, due to enhanced mass and heat transfer at the microscale. More importantly, over 90% radiolabeling yields (incorporation of radiometal) were achieved with a 1:1 stoichiometry of bifunctional chelate biomolecule conjugate (BFC-BM) to radiometal in the microreactor, which potentially obviates extensive chromatographic purification that is typically required to remove the large excess of unlabeled biomolecule in radioligands prepared using conventional methods. Moreover, higher yields for radiolabeling of DOTA-functionalized BSA protein (Bovine Serum Albumin) were observed with ⁶⁴Cu/⁶⁸Ga using the microreactor, which demonstrates the ability to label both small and large molecules. A robust, reliable, compact microreactor capable of chelating radiometals with common chelates has been developed and validated. Based on our radiolabeling results, the reported microfluidic approach overall outperforms conventional radiosynthetic methods, and is a promising technology for the radiometal labeling of commonly utilized BFC-BM in aqueous solutions. Copyright © 2013 Elsevier Inc. All rights reserved.

  8. 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...

  9. Detection of inflammatory lesions with radiolabelled immunoglobulins

    International Nuclear Information System (INIS)

    Blok, D.; Rijksuniversiteit Leiden; Ogtrop, M. van; Arndt, J.W.; Camps, J.A.J.; Feitsma, R.I.J.; Pauwels, E.K.J.

    1990-01-01

    Previous reports on the use of radiolabelled immunoglobulins led us to undertake a pilot experiment in an animal model to investigate the potentials sodium pertechnate Tc 99m-immunoglobulin scintigraphy in the detection of infectious foci. Mice infected in one leg with staphylococcus infection in were injected with sodium pertechnote Tc 99m-immunoglobulin, albumin aggregated technetium Tc 99m or gallium citrate Ga 67. The results obtained by scintigraphy suggested a specific accumulation of radiolabelled immunoglobulin at the site of infection. Visualization of the infection and the image quality, especially the 6- and 24-h images, were clearly enhanced after the use of immunoglobulin preparations as compared with those labelled with gallium. (orig.)

  10. Chitosan Microspheres as Radiolabeled Delivery Devices

    International Nuclear Information System (INIS)

    Permtermsin, Chalermsin; Ngamprayad, Tippanan; Phumkhem, Sudkanung; Srinuttrakul, Wannee; Kewsuwan, Prartana

    2007-08-01

    Full text: This study optimized conditions for preparing, characterizing, radiolabeled of chitosan microspheres and the biodistribution of 99mTc-Chitosan microspheres after intravenous administration. Particle size distribution of the microspheres was determined by light scattering. Zeta potential was studied by dynamic light scattering and electrophoresis technique. Biodistribution studies were performed by radiolabeling using 99mTc. The results shown that geometric mean diameter of the microspheres was found to be 77.26?1.96 ?m. Microsphere surface charge of chitosan microspheres was positive charge and zeta potential was 25.80 ? 0.46 mV. The labeling efficiency for this condition was more than 95% and under this condition was stable for at least 6 h. Radioactivity

  11. Radiolabelled blood elements techniques and clinical applications

    International Nuclear Information System (INIS)

    Thakur, M.L.

    1992-01-01

    Over the past few years, in nuclear medicine, the diagnostic applications of radiolabelled blood elements in general, and of radiolabelled white blood cells in particular, have become increasingly popular. This is primarily due to the introduction of lipid soluble 111 In-oxine as an agent, which not only is an excellent and a reliable tracer for blood cells but also enables the investigators to study the in vivo cell kinetics and map the localization of labelled cells by external gamma scintigraphy. The tracer has the modest half life of 67 hours and decays with the emission of two gamma photons (173 and 247 keV) in high abundance. This technique has provided a powerful tool to study the in vivo cell kinetics in health and localize abnormal lesions in diseases which invoke intense focal cellular concentration

  12. Radiolabelled blood elements techniques and clinical applications

    Energy Technology Data Exchange (ETDEWEB)

    Thakur, M L

    1993-12-31

    Over the past few years, in nuclear medicine, the diagnostic applications of radiolabelled blood elements in general, and of radiolabelled white blood cells in particular, have become increasingly popular. This is primarily due to the introduction of lipid soluble {sup 111}In-oxine as an agent, which not only is an excellent and a reliable tracer for blood cells but also enables the investigators to study the in vivo cell kinetics and map the localization of labelled cells by external gamma scintigraphy. The tracer has the modest half life of 67 hours and decays with the emission of two gamma photons (173 and 247 keV) in high abundance. This technique has provided a powerful tool to study the in vivo cell kinetics in health and localize abnormal lesions in diseases which invoke intense focal cellular concentration 5 figs, 2 tabs

  13. Optimization of IGF-1R SPECT/CT Imaging Using In-111-Labeled F(ab ')(2) and Fab Fragments of Article the Monoclonal Antibody R1507

    NARCIS (Netherlands)

    Heskamp, Sandra; van Laarhoven, Hanneke W. M.; Molkenboer-Kuenen, Janneke D. M.; Bouwman, Wilbert H.; van der Graaf, Winette T. A.; Oyen, Wim J. G.; Boerman, Otto C.

    2012-01-01

    The insulin-like growth factor 1 receptor (IGF-1R) is a potential new target for the treatment of breast cancer. Patients with breast cancer lesions that express IGF-1R may benefit from treatment with anti-IGF-IR antibodies. IGF-1R expression can be visualized using radiolabeled R1507, a monoclonal

  14. Monitoring radiolabelled antacid preparations in the stomach

    International Nuclear Information System (INIS)

    May, H.A.; Wilson, C.G.; Hardy, J.G.

    1984-01-01

    Radiolabelled antacid preparations have been monitored in the stomach using gamma scintigraphy. The stomach contents were labelled with technetium-99m and two antacid preparations with indium-113m. It has been shown that the antacid containing aluminium hydroxide and magnesium oxide mixed and emptied with the other stomach contents. An alginate containing preparation tended to float on the food and emptied only slowly from the stomach. (Auth.)

  15. {sup 99m}Tc radiolabeling and biodistribution study of scorpionfish (Scorpaena plumieri) venom in Swiss mice

    Energy Technology Data Exchange (ETDEWEB)

    Soprani, Juliana; Pujatti, Priscilla B.; Santos, Raquel G. dos [Centro de Desenvolvimento da Tecnologia Nuclear(CDTN/CNEN-MG), Belo Horizonte, MG (Brazil). Lab. de Radiobiologia]. E-mail: falejs@yahoo.com.br; priscillapujatti@yahoo.com.br; santosr@cdtn.br; Figueiredo, Suely G. de [Universidade Federal do Espirito Santo (UFES), Vitoria, ES (Brazil). Depto. de Ciencias Fisiologicas]. E-mail: suelygf@gmail.com; Simal, Carlos [Universidade Federal de Minas Gerais (UFMG), Belo Horizonte, MG (Brazil). Faculdade de Medicina]. E-mail: csimal@brfree.com.br

    2007-07-01

    The use of radiotracers in research of animal venom has been scarce, although it allows an excellent approach to follow the process of biodistribution and kinetics of toxins, and tissue distribution studies are very important for clinical use. Our group has demonstrated that Scorpaena plumieri venom (SP) possess high antitumoral activity and can be a source of template molecules for the development of antitumoral drugs. The purpose of this study was to radiolabel SP with 99mTc and investigate its biodistribution profile. High labeling yield was obtained and the results suggest that [99mTc]SP can be an useful tool for in vivo studies. The analysis indicated that SP is excreted manly by the kidneys with a slow clearance rate. The significant [99mTc]SP uptake in the heart and lungs may explain, at least partially, the pulmonary edema and effect cardiac observed by the envenoming. (author)

  16. Preparation of radiolabeled bioactive asbestos fibers

    Energy Technology Data Exchange (ETDEWEB)

    Tewson, T J; Francsechini, M P; Scheule, R K; Holian, A [Texas Univ., Houston, TX (USA). Health Science Center

    1991-01-01

    We have developed an efficient procedure to radiolabel asbestos fibers while retaining the bioactivity of the fibers. The fibers are labeled with {sup 68}Ge. The {sup 68}Ge decays into {sup 68}Ga, which then can be detected by its characteristic positron emission. Both chrysotile and crocidolite asbestos, a serpentine and an amphibole, respectively, were radiolabeled successfully. Mild reaction conditions and short reaction times were found under which {similar to}90% of the added {sup 68}Ge and {sup 68}Ga bound to the fibers. The radiolabel was retained even after washing the fibers extensively with physiologic buffers. The effects of the labeling on the bioactivity of the fibers were evaluated in an in vitro assay using guinea pig alveolar macrophages as a target cell. Labeled chrysotile fibers were found to retain >95% of their ability to stimulate these cells. The labeling procedure described in this study should be useful in preparing labeled fibers to investigate both in vitro and in vivo phenomena. (author).

  17. 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

  18. Predicting the biodistribution of radiolabeled cMORF effector in MORF-pretargeted mice

    International Nuclear Information System (INIS)

    Liu, Guozheng; Dou, Shuping; He, Jiang; Liu, Xinrong; Rusckowski, Mary; Hnatowich, Donald J.

    2007-01-01

    Pretargeting with phosphorodiamidate morpholino oligomers (MORFs) involves administration of a MORF-conjugated anti-tumor antibody such as MN14 as a pretargeting agent before that of the radiolabeled complementary MORF (cMORF) as the effector. The dosages of the pretargeting agent and effector, the pretargeting interval, and the detection time are the four pretargeting variables. The goal of this study was to develop a semiempirical description capable of predicting the biodistribution of the radiolabeled effector in pretargeted mice and then to compare predictions with experimental results from pretargeting studies in tumored animals in which the pretargeting interval and the detection time were both fixed but the dosages of both the effector and the pretargeting agent were separately varied. Pretargeting studies in LS174T tumored mice were performed using the anti-CEA antibody MN14 conjugated with MORF and the cMORF radiolabeled with 99m Tc. A description was developed based on our previous observations in the same mouse model of the blood and tumor levels of MORF-MN14, accessibility of MORF-MN14 to labeled cMORF, the tumor accumulation of labeled cMORF relative to MORF-MN14 levels therein, and the kidney accumulation of labeled cMORF. The predicted values were then compared with the experimental values. The predicted biodistribution of the radiolabeled effector and the experimental data were in gratifying agreement in normal organs, suggesting that the description of the pretargeting process was reliable. The tumor accumulations occasionally fell outside two standard deviations of that predicted, but after tumor size correction, good agreement between predicted and experimental values was observed here as well. A semiempirical description of the biodistribution of labeled cMORF was capable of predicting the biodistribution of the radiolabeled effector in the pretargeted tumored mouse model, demonstrating that the underlying pretargeting concepts are correct. We

  19. SPECT assay of radiolabeled monoclonal antibodies. Final performance report, March 1992--November 1995

    International Nuclear Information System (INIS)

    Jaszczak, R.J.

    1995-12-01

    Research is described in the following areas: development and evaluation quantitatively of reconstruction algorithms with improved compensations for attenuation, scatter, and geometric collimator response; evaluation of single photon emission computed tomography (SPECT) quantification of iodine 123 and astatine 211; and the development and evaluation of SPECT pinhole imaging for low and medium energy photons

  20. SPECT assay of radiolabeled monoclonal antibodies. Final performance report, March 1992--November 1995

    Energy Technology Data Exchange (ETDEWEB)

    Jaszczak, R.J.

    1995-12-01

    Research is described in the following areas: development and evaluation quantitatively of reconstruction algorithms with improved compensations for attenuation, scatter, and geometric collimator response; evaluation of single photon emission computed tomography (SPECT) quantification of iodine 123 and astatine 211; and the development and evaluation of SPECT pinhole imaging for low and medium energy photons.

  1. Preclinical evaluation of radiolabelled nimotuzumab, a promising monoclonal antibody targeting the epidermal growth factor receptor

    Czech Academy of Sciences Publication Activity Database

    Bárta, P.; Lázníčková, A.; Lázníček, M.; Beckford, Denis R.; Beran, Miloš

    2013-01-01

    Roč. 56, č. 5 (2013), s. 280-288 ISSN 0362-4803 Grant - others:GA ČR(CZ) GAP304/10/1738 Institutional support: RVO:61389005 Keywords : radiopharmaceutical * 177Lu * 131I * nimotuzumab * EGFR * preclinical biodistribution Subject RIV: FR - Pharmacology ; Medidal Chemistry Impact factor: 1.187, year: 2013

  2. Developing the 186 Re radiolabelling procedures of peptides and monoclonal antibodies

    International Nuclear Information System (INIS)

    Lungu, V.; Mihailescu, G.

    1999-01-01

    Mono and poli-clonal antibodies are the most recent candidate molecules for the radiopharmaceutical preparation used in radioimmunotherapy and radiodiagnostic. Our study presents results in 186 Re direct labelling of HIgG (Human Immunoglobulin G) poli-clonal antibody. The steps in labelling process are: 1. pre-reduction -S-S- bridges of HIgG molecule with ascorbic acid in pH = 3.5 - 4.5; 2. preparation of the reducing system for 186 ReO 4 - in presence of Sn 2+ ions excess and 3. coupling 186 Re (red) to -SH groups of biomolecules. The specific reactions of each step above are controlled by: incubation time and temperature, pH, molar ratio 186 Re: HIgG. 186 Re-HIgG samples were purified by gel elution chromatography method and the quality control was performed by chromatography techniques. To labelled of HIgG we effected the pre-reduction of -S-S- bridges of biomolecules to sulfhydryls using the following reducing agents: ascorbic acid, cysteine, active hydrogen, 2,3 dimercaptopropanol. The pre-reduction reactions are controlled by mass ratios of reduction agent/biomolecule, pH, temperature and time of incubation. HIgG was the biomolecule used in the pre-reduction reactions. The specific parameters for each systems are presented. The stannous chloride was used as reducing agent in two systems, SnCl 2 : 0.05 N HCl and SnCl 2 : 20 mg/ml citric acid. The coupling reaction of 186 Re (red) with the biomolecule has been controlled by time and incubation temperature and the influence of pH regarding the binding of 186 Re to the biomolecule. 186 Re-HIgG was obtained by: i) incubation at the room temperature, 1 hour time of HIgG in thiol form and 186 Re in reducing form and ii) incubation of HIgG in thiol form, at 37 deg C and 22 hours time, with adding after pre-reduction of SnCl 2 and Na 186 ReO 4 . Quality control was effected by chromatography techniques (paper and gel chromatography) on labelled biomolecule before and after purification. The elution gel chromatography was spectrophotometrically monitored at 280 nm. At the same time the radioactivity of elution samples was measured using a gamma counter. The radiochemical purity of 186 Re - HIgG was determined by Whatman 1 paper chromatography in the following solvents: acetone, ethanol and ethanol: NH 3 : H 2 O (2: 1: 5). Good results were obtained for 186 Re - HIgG prepared in pre-reduction conditions with 1) ascorbic acid and 2) Sn : citric acid at 4 and 3.5 pH. (authors)

  3. Radiolabelled peptides: New radiopharmaceuticals for targeted therapy

    International Nuclear Information System (INIS)

    Chinol, M.

    2001-01-01

    Radiolabelled peptides have been the focus of an increasing interest by the nuclear medicine community within the last few years. This has mainly been due to successful development of one of these peptides, somatostatin, as a tool to visualise various pathologic conditions known to express a high number of somatostatin receptors. Somatostatin receptors have been identified in different tumours such as neuroendocrine tumours, tumours of the central nervous system, breast, lung and lymphatic tissue. These observations served as the biomolecular basis for the clinical use of radiolabelled somatostatin analogs, which are at present of great interest for diagnostic and therapeutic applications. A promising somatostatin analogue, DOTA-D-Phe 1 -Ty 3 -octreotide, named DOTATOC, has shown favourable biodistribution and high affinity binding to SSTR2 and SSTR5, high hydrophilicity and ease of labelling and stability with 111 In and 90 Y. A clinical trial aimed at evaluating the biodistribution and dosimetry of DOTATOC radiolabelled with 111 In, in anticipation of therapy trials with 90 Y-DOTATOC in patients was undertaken. 111 In-DOTATOC showed favourable pharmacokinetics (fast blood clearance and urinary excretion) and biodistribution, and high affinity to tumours expressing somatostatin receptors (thus, a high residence time in tumour). These results are promising for therapy trials with 90 Y-DOTAOC, for which radiation dosimetry appears acceptable for normal organs (including the red marrow). Moreover, labelling conditions of DOTATOC with 90 Y has been optimised in order to achieve labelling yields of more than 98% and specific activities of greater than 60 GBq (1.6 Ci)/μmol. (author)

  4. Radiolabeling Of Albumin Particles With Yttrium-90

    International Nuclear Information System (INIS)

    Nguyen Thi Thu; Nguyen Thi Khanh Giang; Bui Van Cuong, Vo Thi Cam Hoa

    2011-01-01

    This paper presents the process of the radiolabeling of microaggregated albumin particles with radionuclide Yttrium-90 using the directed method. The albumin microsphere kit was prepared in sodium phosphate buffer. The original solution includes 2 mg albumin particle and 0.5 mg stannous chloride dihydrate. The albumin particles size was ranged from 5 ?m to 30 ?m. The mixture was washed three times with phosphate buffer saline, pH 7.2 by centrifugation and suspended in 0.5 M sodium acetate buffer, pH 6. Yttrium - 90 in 1.0 M acetic acid was collected from 90 Sr/ 90 Y generator. The labeling of the particles with Y-90 (185 MBq) was performed at pH 5.5 in acetate buffer with agitating for 60 min at room temperature. The labeled albumin suspensions were centrifuged at 3000 rpm for 15 min. Labeling yields was calculated using centrifugation, filtration and compared with paper chromatography, which is developed in the Tris Acetic EDTA. In this system, the unbound of Y-90 migrates to an R f of 0.9-1.0 and the radiolabeled albumin particles remains at the point of origin (R f = 0). The size of 90 Y-albumin particles was compared with the albumin particles in the original solution to be sure that they did not change during the labeling treatment. The radiolabeling yields were more than 80%. The labeled compound was dialysis in phosphate buffer. The radiochemical purity was 98%. The 90 Y- albumin is an ideal radiopharmaceutical for potential use in malignant cancer treatment as brachytherapy. (author)

  5. Breast cancer imaging using radiolabelled somatostatin analogues

    International Nuclear Information System (INIS)

    Dalm, Simone U.; Melis, Marleen; Emmering, Jasper; Kwekkeboom, Dik J.; Jong, Marion de

    2016-01-01

    Imaging and therapy using radiolabelled somatostatin analogues are methods successfully used in patients with somatostatin receptor (SSTR)-expressing neuroendocrine tumours. Since these techniques were first introduced, many improvements have been made. SSTR expression has also been reported on breast cancer (BC). Currently mammography, magnetic resonance imaging and ultrasound are the most frequent methods used for BC imaging. Since SSTR expression on BC was demonstrated, clinical studies examining the feasibility of visualizing primary BC using SSTR radioligands have been performed. However, to date SSTR-mediated nuclear imaging is not used clinically in BC patients. The aim of this review is to assess whether recent improvements made within nuclear medicine may enable SSTR-mediated imaging to play a role in BC management. For this we critically analysed results of past studies and discussed the potential of the improvements made within nuclear medicine on SSTR-mediated nuclear imaging of BC. Seven databases were searched for publications on BC imaging with SSTR radioligands. The papers found were analysed by 3 individual observers to identify whether the studies met the pre-set inclusion criteria defined as studies in which nuclear imaging using radiolabelled SST analogues was performed in patients with breast lesions. Twenty-four papers were selected for this review including studies on SSTR-mediated nuclear imaging in BC, neuroendocrine BC and other breast lesions. The analysed studies were heterogeneous with respect to the imaging method, imaging protocol, patient groups and the radiolabelled SST analogues used. Despite the fact that the analysed studies were heterogeneous, sensitivity for primary BC ranged from 36–100%. In a subset of the studies LN lesions were visualized, but sensitivity was lower compared to that for primary tumours. A part of the studies included benign lesions and specificity ranged from 22–100%. Furthermore, false negatives and

  6. Embolus radiolabelling in a new canine model

    International Nuclear Information System (INIS)

    Kaufman, H.H.; Huchton, J.D.; Woo, J.; Cannon, D.C.; Anderson, J.H.

    1980-01-01

    Embolus radiolabelling with 131 I fibrinogen was studied in a canine model of internal carotid artery embolization. The dog was chosen as the experimental animal because of its maxillocarotid artery which permits collateral flow round the occlusion and helps to prevent strokes. Clot was prepared by incubating blood at room temperature to inactivate plasminogen activators and then refrigerating it to promote clot retraction. Emboli persisting 48 hours were seen in 80% of animals. Major strokes were not seen when 0.25 to 0.30 cm 3 were used. Autoradiography and well counting revealed uptake of isotope. The test, when refined, should provide a tool for the investigation of thromboemboli. (author)

  7. Radiolocalization of bovine lymphosarcoma cells in athymic mice, using a monoclonal antibody against tumor-associated antigens

    International Nuclear Information System (INIS)

    Aida, Y.; Ochiai, K.; Ito, K.; Onuma, M.; Fujimori, F.; Fujimoto, Y.; Izawa, H.

    1987-01-01

    Mouse monoclonal antibody c 143 was purified and F(ab')2 fragments were generated by pepsin digestion and then radiolabeled with 125 I. The 125 I-labeled c 143 F(ab')2 fragments were injected into athymic mice bearing bovine lymphoid tumor cells. The fragments became preferentially localized in tumor tissues, but not in normal tissues, as determined by differential counting of tissue radioactivity. The fragments became localized specifically in those tumors that were reactive with c 143 in vitro, but did not become localized in unrelated tumors. Localization of labeled F(ab')2 fragments of a monoclonal antibody of the same isotype directed against Taka virus (a variant of Newcastle disease virus) was not observed in athymic mice bearing bovine lymphoid tumor cells. Tumors were detectable by radioimmunoscintigraphy, using radiolabeled c 143 F(ab')2 fragments, without background subtraction, and by use of silver-grain scattering in light microscopic autoradiography

  8. Radiolabeling of anti-CD20 with Re0-188: liquid kit

    Energy Technology Data Exchange (ETDEWEB)

    Dias, Carla Roberta; Osso Junior, Joao Alberto [Instituto de Pesquisas Energeticas e Nucleares (IPEN/CNEN-SP), Sao Paulo, SP (Brazil)]. E-mail: carlarobertab@yahoo.com.br; jaosso@ipen.br

    2007-07-01

    Radioimmunotherapy uses the targeting features of monoclonal antibody to deliver radiation from an attached radionuclide. The radionuclide {sup 188}Re is currently produced from the father nuclide {sup 188}W through a transportable generator system. Because of its easy availability and suitable nuclear properties (E{sub {beta}}{sub MAX} =2.1 MeV, t{sub 1/2}=16.9 h, E{sub {gamma}}=155 keV), this radionuclide is considered an attractive candidate for application as therapeutic agents and could be conveniently utilized for imaging and dosimetric purposes. The objective of this work is the optimization of radiolabeling of anti-CD20 with {sup 188}Re using a liquid formulation. Anti-CD20 was reduced by incubation with 2-ME and purified over a PD-10 column. The number of resulting free SH was assayed with Ellman's reagent. Optimization of radiolabeling was achieved by varying parameters: antibody mass, reducing agent, reaction time and {sup 188}Re volume in the liquid kit. Radiochemical purity of {sup 188}Re-anti-CD20 was evaluated. An average of 12 SH groups per mol in the reductions was found. The best labeling efficiency (> 93%) was achieved in the following conditions: 1 mg anti-CD20; 82.8 mg sodium tartrate; 1 mg SnCl{sub 2}; 0.25 mg gentisic acid, 1 mL {sup 188}Re and reaction time of 1 hour at room temperature. (author)

  9. Radiolabeling of anti-CD20 with Re0-188: liquid kit

    International Nuclear Information System (INIS)

    Dias, Carla Roberta; Osso Junior, Joao Alberto

    2007-01-01

    Radioimmunotherapy uses the targeting features of monoclonal antibody to deliver radiation from an attached radionuclide. The radionuclide 188 Re is currently produced from the father nuclide 188 W through a transportable generator system. Because of its easy availability and suitable nuclear properties (E βMAX =2.1 MeV, t 1/2 =16.9 h, E γ =155 keV), this radionuclide is considered an attractive candidate for application as therapeutic agents and could be conveniently utilized for imaging and dosimetric purposes. The objective of this work is the optimization of radiolabeling of anti-CD20 with 188 Re using a liquid formulation. Anti-CD20 was reduced by incubation with 2-ME and purified over a PD-10 column. The number of resulting free SH was assayed with Ellman's reagent. Optimization of radiolabeling was achieved by varying parameters: antibody mass, reducing agent, reaction time and 188 Re volume in the liquid kit. Radiochemical purity of 188 Re-anti-CD20 was evaluated. An average of 12 SH groups per mol in the reductions was found. The best labeling efficiency (> 93%) was achieved in the following conditions: 1 mg anti-CD20; 82.8 mg sodium tartrate; 1 mg SnCl 2 ; 0.25 mg gentisic acid, 1 mL 188 Re and reaction time of 1 hour at room temperature. (author)

  10. Intravenous avidin chase improved localization of radiolabeled streptavidin in intraperitoneal xenograft pretargeted with biotinylated antibody

    International Nuclear Information System (INIS)

    Zhang Meili; Sakahara, Harumi; Yao Zhengsheng; Saga, Tsuneo; Nakamoto, Yuhi; Sato, Noriko; Nakada, Hiroshi; Yamashina, Ikuo; Konishi, Junji

    1997-01-01

    In the present study, we examined the effect of avidin administered intravenously (i.v.) on the biodistribution of radiolabeled streptavidin in mice bearing intraperitoneal (IP) xenografts pretargeted with biotinylated antibody. Tumors were established in nude mice by IP inoculation of LS180 human colon cancer cells. Monoclonal antibody MLS128, which recognizes Tn antigen on mucin, was biotinylated and injected IP into the IP tumor-bearing mice. Radioiodinated streptavidin was administered IP or i.v. 48 h after pretargeting of biotinylated antibody. Avidin was administered i.v. 30 min prior to streptavidin injection. The localization of radioiodinated streptavidin in the tumor pretargeted with biotinylated antibody was significantly higher than that without pretargeting and that of radioiodinated MLS128 by the one-step method. Avidin administration significantly accelerated the clearance of radioiodinated streptavidin in blood and other normal tissues and increased the tumor-to-blood radioactivity ratio regardless of administration route of streptavidin. The i.v. avidin chase improved tumor localization of radiolabeled streptavidin in the IP xenografts pretargeted with biotinylated antibody

  11. Localization of 111In- and 125I-labeled monoclonal antibody in guinea pigs bearing line 10 hepatocarcinoma tumors

    International Nuclear Information System (INIS)

    Bernhard, M.I.; Hwang, K.M.; Foon, K.A.

    1983-01-01

    A murine monoclonal antibody (D3) with demonstrated specificity for the guinea pig line 10 hepatocarcinoma (L10) was radiolabeled with either 125 I or 111 In and used to image dermal tumors in vivo. In one set of experiments, L10 tumors were established middorsally in one group of animals, and the similarly derived, antigenically distinct line 1 tumor was established in another group of animals. In spite of background imaging of liver, kidney, and spleen, L10 tumors were visualized clearly. Incorporation of radiolabel was demonstrated to predominate in the L10 tumor. In a separate set of experiments, L10 and line 1 tumors were established in contralateral thighs in the same animals. L10 tumors were visualized clearly, and tissue uptake of radiolabel was demonstrated to reside predominantly in the L10 tumor

  12. Positron emission tomographic imaging of tumors using monoclonal antibodies. Progress report, April 15, 1992--October 31, 1992

    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.

  13. 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...

  14. Radiolabeled amino acids : Basic aspects and clinical applications in oncology

    NARCIS (Netherlands)

    Jager, PL; Vaalburg, W; Pruim, J; de Vries, EGE; Langen, KJ; Piers, DA

    As the applications of metabolic imaging are expanding, radiolabeled amino acids may gain increased clinical interest, This review first describes the basic aspects of amino acid metabolism, then continues with basic aspects of radiolabeled amino acids, and finally describes clinical applications,

  15. Application of 99mTc-labeled chimeric Fab fragments of monoclonal antibody A7 for radioimmunoscintigraphy of pancreatic cancer

    International Nuclear Information System (INIS)

    Matsumura, Hiroomi

    1999-01-01

    Pancreatic cancer is one of the most lethal diseases and its prognosis is still poor. To improve the survival rate, it is essential to develop new technologies for early and definitive diagnosis. In this study, chimeric Fab fragments of monoclonal antibody A7 were successfully radio-labeled with 99m Tc, preventing depression of the antigen-binding activity. 99m Tc-labeled monoclonal antibody A7, 99m Tc-labeled chimeric Fab fragments of monoclonal antibody A7, 99m Tc-labeled normal mouse IgG and 99m Tc-labeled Fab fragments of normal mouse IgG were injected intravenously into nude mice bearing human pancreatic cancer xenografts and the radioactivity was subsequently measured. The tumor accumulation was significantly higher with labeled monoclonal antibody A7 than with normal mouse IgG, and higher with chimeric Fab fragments of monoclonal antibody A7 than with Fab fragments of normal mouse IgG. The tumor/blood ratio of radioactivity increased rapidly over time with chimeric Fab fragments of monoclonal antibody A7. These results suggest that chimeric Fab fragments of monoclonal antibody A7 may be useful for diagnosing pancreatic cancer by means of radioimmunoscintigraphy. (author)

  16. 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

  17. Monoclonal antibodies reactive with human breast or ovarian carcinoma: In vivo applications

    International Nuclear Information System (INIS)

    Thor, A.D.; Edgerton, S.M.

    1989-01-01

    Monoclonal antibodies (MoAbs) are unique and useful bioprobes that allow in vivo targeting of membrane-associated or circulating antigens. Most of the clinical trials to date have used low dosages of radiolabeled MoAb given in a single dose. Newer studies have included antibody fragments, repeated injections, intraperitoneal (IP) administration, and other labels such as 90Y. Clinical MoAb trials are often arduous, expensive, and time-consuming to perform. Before human use, animal studies and extensive MoAb characterization are required. The production of pharmaceutical grade, radiolabeled MoAb is technically difficult and costly. Clinical trials require administrative and patient consent as well as extensive written protocols. These studies necessitate interdepartmental and intradepartmental cooperation and coordination. Furthermore, the use of in vivo radiolabeled probes impacts many levels of health care providers from janitorial, nursing, and technical staff to laboratories and physicians. Simple blood tests or disposal of body excretions may concern nursing or technical staff with the possibility of radiation exposure. The responsibility for study design, personnel involvement, and prospective use in patients without a definitive cancer diagnosis ultimately rests with the physician. While many issues have been addressed, additional clinical trials, consideration of safety issues, and standardization between institutions will be necessary before the use of radiolabeled MoAb for diagnosis, management, or therapy of human tumors becomes routine. Continued cooperation and funding should ensure its achievement. 136 references

  18. Mycobacterium leprae antigens involved in human immune responses. I. Identification of four antigens by monoclonal antibodies

    Energy Technology Data Exchange (ETDEWEB)

    Britton, W.J.; Hellqvist, L.; Basten, A.; Raison, R.L.

    1985-12-01

    Four distinct antigens were identified in soluble sonicates of Mycobacterium leprae by using a panel of 11 monoclonal antibodies. Cross-reactivity studies with other mycobacterial species were conducted by using ELISA and immunoblot assays, and demonstrated that determinants on two of the antigens were present in many mycobacteria, whereas the other two were limited in distribution. Competitive inhibition experiments with radiolabeled monoclonal antibodies showed cross-inhibition between antibodies identifying two of the four antigenicbands. These two bands, of M/sub tau/ 4.5 to 6 KD and 30 to 40 KD, were resistant to protease treatment after immunoblotting. In contrast the two other bands of 16 and 70 KD were protease-sensitive. Although all four bands reacted with some human lepromatous leprosy sera in immunoblots, the 4.5 to 6 KD and 30 to 40 KD bands were most prominent. Lepromatous leprosy sera also inhibited the binding of radiolabeled monoclonal antibodies to each of the four antigens, with the mean titer causing 50% inhibition being higher for antibodies reacting with the 4.5 to 6 KD and 30 to 40 KD bands. These findings indicated that all four antigens were involved in the human B cell response to M. leprae.

  19. Mycobacterium leprae antigens involved in human immune responses. I. Identification of four antigens by monoclonal antibodies

    International Nuclear Information System (INIS)

    Britton, W.J.; Hellqvist, L.; Basten, A.; Raison, R.L.

    1985-01-01

    Four distinct antigens were identified in soluble sonicates of Mycobacterium leprae by using a panel of 11 monoclonal antibodies. Cross-reactivity studies with other mycobacterial species were conducted by using ELISA and immunoblot assays, and demonstrated that determinants on two of the antigens were present in many mycobacteria, whereas the other two were limited in distribution. Competitive inhibition experiments with radiolabeled monoclonal antibodies showed cross-inhibition between antibodies identifying two of the four antigenicbands. These two bands, of M/sub tau/ 4.5 to 6 KD and 30 to 40 KD, were resistant to protease treatment after immunoblotting. In contrast the two other bands of 16 and 70 KD were protease-sensitive. Although all four bands reacted with some human lepromatous leprosy sera in immunoblots, the 4.5 to 6 KD and 30 to 40 KD bands were most prominent. Lepromatous leprosy sera also inhibited the binding of radiolabeled monoclonal antibodies to each of the four antigens, with the mean titer causing 50% inhibition being higher for antibodies reacting with the 4.5 to 6 KD and 30 to 40 KD bands. These findings indicated that all four antigens were involved in the human B cell response to M. leprae

  20. Anti-CD20 Immunoglobulin G Radiolabeling with a 99mTc-Tricarbonyl Core: In Vitro and In Vivo Evaluations.

    Directory of Open Access Journals (Sweden)

    Hélène Carpenet

    Full Text Available In recent years, the diagnostic and therapeutic uses of radioisotopes have shown significant progress. Immunoglobulin (Ig appears to be a promising tracer, particularly due to its ability to target selected antigens. The main objective of this study is to optimize and assess an Ig radiolabeling method with Technetium 99m (99mTc, an attractive radioelement used widely for diagnostic imaging. Monoclonal anti-CD20 IgG was retained to study in vitro and in vivo radiolabeling impact. After IgG derivatization with 2-iminothiolane, IgG-SH was radiolabeled by an indirect method, using a 99mTc-tricarbonyl core. Radiolabeling stability was evaluated over 24h by thin-layer chromatography. IgG integrity was checked by sodium dodecyl sulfate-polyacrylamide gel electrophoresis coupled with Western blot and autoradiography. The radiolabeled Ig's immunoaffinity was assessed in vitro by a radioimmunoassay method and binding experiments with cells (EL4-hCD20 and EL4-WT. Biodistribution studies were performed in normal BALB/c mice. Tumor uptake was assessed in mice bearing EL4-hCD20 and EL4-WT subcutaneous xenografts. With optimized method, high radiolabeling yields were obtained (95.9 ± 3.5%. 99mTc-IgG-SH was stable in phosphate-buffered saline (4°C and 25°C and in serum (37°C, even if important sensitivity to transchelation was observed. IgG was not degraded by derivatization and radiolabeling, as shown by Western blot and autoradiography results. 99mTc-anti-CD20 IgG-SH immunoaffinity was estimated with Kd = 35 nM by both methods. In vivo biodistribution studies for 48h showed significant accumulation of radioactivity in plasma, liver, spleen, lungs and kidneys. Planar scintigraphy of mice bearing tumors showed a significant uptake of 99mTc-anti-CD20 IgG-SH in CD20+ tumor versus CD20- tumor. Radiolabeling of derivatized IgG with 99mTc-tricarbonyl was effective, stable and required few antibody amounts. This attractive radiolabeling method is "antibody safe

  1. 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

  2. Possible therapeutic use of radiolabeled cisplatin

    Energy Technology Data Exchange (ETDEWEB)

    Leal, Alexandre S.; Bernardes, Felipe D.; Gonçalves, Natalia A.Z., E-mail: asleal@cdtn.br [Centro de Desenvolvimento da Tecnologia Nuclear (CDTN/CNEN-MG), Belo Horizonte, MG (Brazil)

    2017-07-01

    The cisplatin, cis-diamminedichloroplatinum (II), (NH{sub 3}){sub 2}PtCl{sub 2} or (CDDP) is a very common chemotherapeutical agent used in the treatment of ovary, lungs, testicle, head and neck carcinoma. It has been used for treatment of numerous human cancers including bladder, head and neck, lung, ovarian, and testicular cancers. However, because of the drug resistance and numerous undesirable side effects, a lot of work involving new formulations or administration of the CDDP has been done. In this work, we present a preliminary discussion about the possibilities of using the radiolabeled CDDP or CDDP⁎, as new alternative therapy. The works based on previous very positive in-vitro results of using the CDDP⁎ compared to CDDP in the cytotoxic effect of some kind of tumor cells. The preparation and characterization of the CDDP⁎ as well as the dose of CDDP⁎ required are presented and discussed. (author)

  3. Possible therapeutic use of radiolabeled cisplatin

    International Nuclear Information System (INIS)

    Leal, Alexandre S.; Bernardes, Felipe D.; Gonçalves, Natalia A.Z.

    2017-01-01

    The cisplatin, cis-diamminedichloroplatinum (II), (NH 3 ) 2 PtCl 2 or (CDDP) is a very common chemotherapeutical agent used in the treatment of ovary, lungs, testicle, head and neck carcinoma. It has been used for treatment of numerous human cancers including bladder, head and neck, lung, ovarian, and testicular cancers. However, because of the drug resistance and numerous undesirable side effects, a lot of work involving new formulations or administration of the CDDP has been done. In this work, we present a preliminary discussion about the possibilities of using the radiolabeled CDDP or CDDP⁎, as new alternative therapy. The works based on previous very positive in-vitro results of using the CDDP⁎ compared to CDDP in the cytotoxic effect of some kind of tumor cells. The preparation and characterization of the CDDP⁎ as well as the dose of CDDP⁎ required are presented and discussed. (author)

  4. Autodecomposition of radiolabeled human growth hormone

    International Nuclear Information System (INIS)

    Baumann, G.; Amburn, K.

    1986-01-01

    Human growth hormone (hGH) was radiolabeled with 125 I, using a gentle lactoperoxidase technique. The stability and decomposition products of this tracer were studied by frequent periodic analysis by Sephadex G-100 chromatography on a long column. Monomeric 125 I-hGH showed an exponential decline, with a half-life of 61 days. The main radioactive degradation product was iodide, which appeared with a fractional appearance rate of 0.01136 per day. Secondary degradation products were a series of radioactive oligomers of hGH, which appeared with an overall fractional rate of 0.00525 per day. The kinetic data obtained should provide guidelines for the shelf-life and repurification schedule of radioiodinated polypeptides

  5. 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

  6. Development of a stable radioiodinating reagent to label monoclonal antibodies for radiotherapy of cancer

    International Nuclear Information System (INIS)

    Wilbur, D.S.; Hadley, S.W.; Hylarides, M.D.; Abrams, P.G.; Beaumier, P.A.; Morgan, A.C.; Reno, J.M.; Fritzberg, A.R.

    1989-01-01

    A method of radioiodinating monoclonal antibodies such that the labeled antibodies do not undergo in vivo deiodination has been studied. The method utilizes conjugation of succinimidyl para-iodobenzoate to the antibody. The iodobenzoate was radiolabeled by using an organometallic intermediate to facilitate the reaction. Thus, succinimidyl para-tri-n-butylstannylbenzoate was radiolabeled in 60-90% radiochemical yield and subsequently conjugated to the antibody in 80-90% yield. Animal biodistribution studies were carried out with two separate anti-melanoma antibodies (9.2.27 and NR-M1-05) labeled by this method, and examined in nude mice bearing human melanoma tumor xenografts. Very large differences in the localization of radioactivity were observed in the thyroids and stomachs of mice when the iodobenzoyl-labeled antibodies were compared with the same antibodies labeled using the chloramine-T method of radioiodination. Few other significant differences in the tissue distribution of the radioiodinated antibodies were seen

  7. 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

  8. Preparation and biodistribution of radiolabeled fullerene C60 nanocrystals

    International Nuclear Information System (INIS)

    Nikolic, Nadezda; Vranjes-Duric, Sanja; Jankovic, Drina; Dokic, Divna; Mirkovic, Marija; Bibic, Natasa; Trajkovic, Vladimir

    2009-01-01

    The present study describes for the first time a procedure for the radiolabeling of fullerene (C 60 ) nanocrystals (nanoC 60 ) with Na 125 I, as well as the biodistribution of radiolabeled nanoC 60 ( 125 I-nanoC 60 ). The solvent exchange method with tetrahydrofuran was used to make colloidal water suspensions of radiolabeled nanoC 60 particles. The radiolabeling procedure with the addition of Na 125 I to tetrahydrofuran during dissolution of C 60 gave a higher radiochemical yield of radiolabeled nanoC 60 particles in comparison to the second option, in which Na 125 I was added after C 60 was dissolved. Using photon correlation spectroscopy and transmission electron microscopy, 125 I-nanoC 60 particles were found to have a crystalline structure and a mean diameter of 200-250 nm. The 125 I-nanoC 60 had a particularly high affinity for human serum albumin, displaying 95% binding efficiency after 1 h. Biodistribution studies of 125 I-nanoC 60 in rats indicated significant differences in tissue accumulation of 125 I-nanoC 60 and the radioactive tracer Na 125 I. The higher accumulation of radiolabeled nanoC 60 was observed in liver and spleen, while accumulation in thyroid, stomach, lungs and intestines was significantly lower in comparison to Na 125 I. In addition to being useful for testing the biological distribution of nanoC 60 , the described radiolabeling procedure might have possible applications in cancer radiotherapy.

  9. System for exposing animals to radiolabeled diesel exhaust

    International Nuclear Information System (INIS)

    Lopez, J.A.; Wolf, I.; Wolff, R.K.; Sun, J.D.; Mokler, B.V.

    1981-01-01

    One approach to determining the deposition and fate of inhaled diesel particles is the conduct of inhalation exposure studies with radiolabeled diesel fuel. A system was designed, constructed and tested for the simultaneous exposure of animals to radiolabeled diesel exhaust and collection of large quantities of radiolabeled diesel exhaust particles from a single cylinder diesel engine. The system performance was characterized and evaluated over a range of operating conditions: 0 to 1800 watts of engine load, 1000 to 2500 rpm and dilution air rates of 1:2 and 1:10. The exposure system met required design and operating criteria for safety, portability, space and flexibility

  10. 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...

  11. 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)

  12. 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.)

  13. Enhancement by gamma-interferon of in vivo tumor radiolocalization by a monoclonal antibody against HLA-DR antigen

    International Nuclear Information System (INIS)

    Rowlinson, G.; Balkwill, F.; Snook, D.; Hooker, G.; Epenetos, A.A.

    1986-01-01

    Athymic nu/nu (nude) mice bearing s.c. human breast tumors were treated systemically with recombinant human gamma-interferon. These tumors were phenotypically negative for HLA-DR prior to therapy, but after 4 days of treatment, 80% of the cells expressed this antigen in vivo as assessed by immunoperoxidase (F. R. Balkwill et al., Eur. J. Cancer Clin. Oncol., in press, 1986). A radioiodine-labeled murine monoclonal antibody (TAL-1B5) against HLA-DR specifically localized to the tumors in recombinant human gamma-interferon-treated but not in control mice. An isotype-identical murine monoclonal antibody that did not react with control or recombinant human gamma-interferon-treated tumors did not show any specific localization. These results demonstrate that specific localization to tumors of radio-labeled monoclonal antibodies to HLA-DR can be facilitated by systemic therapy with gamma-interferon

  14. The role of radiolabelled compounds in preclinical drug development

    International Nuclear Information System (INIS)

    Hawkins, D.R.

    1988-01-01

    The role of radiolabelled compounds in the development of new drugs is discussed, with particular reference to their use in toxicological, metabolic and pharmacokinetic studies for the pre-clinical safety evaluation of new drugs. (U.K.)

  15. A new technique for radiolabelling of humic substances

    Energy Technology Data Exchange (ETDEWEB)

    Franke, K.; Patt, J.T.; Patt, M.; Kupsch, H.; Steinbach, J. [Inst. of Interdisciplinary Isotope Research, Leipzig (Germany)

    2004-07-01

    A new method of radiolabelling of humic substances (HS) in the aqueous phase has been developed. Radiolabelling with the short-lived positron-emitter {sup 18}F was carried out via diazonium coupling to electron-rich aromatic residues of the humic substances. Labelling yields of up to 75% were obtained after optimization of the synthetic procedure. Introductory experimental steps were performed for testing the labelling stability of the humic substances with ultrafiltration, electrophoretic and chromatographic methods. (orig.)

  16. A new technique for radiolabelling of humic substances

    International Nuclear Information System (INIS)

    Franke, K.; Patt, J.T.; Patt, M.; Kupsch, H.; Steinbach, J.

    2004-01-01

    A new method of radiolabelling of humic substances (HS) in the aqueous phase has been developed. Radiolabelling with the short-lived positron-emitter 18 F was carried out via diazonium coupling to electron-rich aromatic residues of the humic substances. Labelling yields of up to 75% were obtained after optimization of the synthetic procedure. Introductory experimental steps were performed for testing the labelling stability of the humic substances with ultrafiltration, electrophoretic and chromatographic methods. (orig.)

  17. Radiolabelling of RC-160: preliminary results

    International Nuclear Information System (INIS)

    Verdera, E.S.; Balter Binsky, H.S.; Robles, A.M.; Rodriguez, G.; Souto, B.; Laiz, J.; Oliver, P.; Leon, E.

    1998-01-01

    Vapreotide (RC-160) was labelled with 125 I using Chloramine-T and Iodogen methods and with 99m Tc by a direct method with sodium ditionite as reducing agent in the presence of ascorbic acid. Several methods of purification and quality control were evaluated. Yields of the reactions and of purification steps were calculated. The results obtained for the radioiodination reactions showed higher yields when limiting Chloramine-T method was used. Labelling of RC-160 with 99m Tc indicated better yields when high radioactivity concentration of the radionuclide was used. Stability of the products obtained was assessed at different post-labelling times by selected quality control methods: Sep-Pak cartridge as purification method and chromatography by RP-HPLC and ITLC-SG using saline solution as solvent. It was demonstrated that I-125-RC-160 and Tc-99m-RC-160 were stable during five weeks (at -20 deg. C) and 6 hours (at room temperature) respectively. Preliminary biodistribution of Tc-99m-RC-160 in normal rats and mice were done showing different biological behaviour compared with control animals injected with pertechnetate. In conclusion, RC-160 was successfully labelled with both radionuclides, with radiochemical purity higher than 95%. These results encourage further research work in animal models as well as to investigate the biochemical behaviour of radiolabelled peptide. (author)

  18. Research co-ordination meeting on labelling, quality control and clinical evaluation of monoclonal antibodies for scintigraphy, Kuala Lumpur, Malaysia, 9-13 September 1991

    International Nuclear Information System (INIS)

    1991-09-01

    The Co-ordinated Research Programme (CRP) on ''Labelling, quality control and clinical evaluation of monoclonal antibodies for scintigraphy'' arose from the deliberations at an IAEA Consultants' Meeting (CM) on ''Radiolabelling techniques of monoclonal antibodies'' held in Vienna on 22-24 August 1988. The following is a brief description of the relevant recommendations arising from said meeting. A more detailed description of the proceedings may be found in the summary report issued on 8 December 1989. This report incorporates the results of the first Research Co-ordination Meeting (RCM) of subject CRP held in Kuala Lumpur, Malaysia on 9-13 September 1991. 9 refs

  19. 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.

  20. 99mTc-rituximab radiolabelled by photo-activation: a new non-Hodgkin's lymphoma imaging agent

    International Nuclear Information System (INIS)

    Gmeiner Stopar, T.; Fettich, J.; Hojker, S.; Mlinaric-Rascan, I.; Mather, S.J.

    2006-01-01

    Rituximab was the first chimeric monoclonal antibody to be approved for treatment of indolent B-cell non-Hodgkin's lymphoma (NHL). It is directed against the CD20 antigen, which is expressed by 95% of B-cell NHLs. The aim of this study was to explore the possibility of radiolabelling rituximab with 99m Tc for use as an imaging agent in NHL for early detection, staging, remission assessment, monitoring for metastatic spread and tumour recurrence, and assessment of CD20 expression prior to (radio)immunotherapy. Rituximab was purified from Mabthera solution (Roche), photo-activated at 302 nm by UV irradiation and radiolabelled with 99m Tc. The effectiveness of the labelling method was evaluated by determination of the number of free thiol groups per photoreduced antibody, radiochemical purity and in vitro stability of 99m Tc-rituximab. On average, 4.4 free thiol groups per photoreduced antibody were determined. Radiolabelling yields greater than 95% were routinely observed after storage of the photo-activated antibody at -80 C for 195 days. The direct binding assay showed preserved ability of 99m Tc-rituximab to bind to CD20, with an average immunoreactive fraction of 93.3%. The internalisation rate was proven to be low, with only 5.3% of bound 99m Tc-rituximab being internalised over 4 h at 37 C. Our results demonstrate that 99m Tc-rituximab of high radiochemical purity and with preserved binding affinity for the antigen can be prepared by photoreduction and that the method shows good reproducibility. 99m Tc-rituximab will be further explored as an imaging agent applicable in NHL for the purposes mentioned above. (orig.)

  1. Chemical radiolabeling of carboxyatractyloside by [14C]acetic anhydride

    International Nuclear Information System (INIS)

    Block, M.R.; Pougeois, R.; Vignais, P.V.

    1980-01-01

    The authors report the synthesis and biological properties of a radiolabeled derivative of CAT obtained with acetylation of the primary alcohol of CAT with radiolabeled acetic anhydride. They also investigate the question of mutual exclusion of CAT and BA for binding to the mitochondrial ADP/ATP carrier in double labeling experiments based on the use of [ 3 H]BA and [ 14 C]Ac-CAT. The results are consistent with the view that the ADP/ATP carrier possesses two separate interacting binding sites for AT (or CAT) and for BA. (Auth.)

  2. Positron Emission Tomography Imaging Using Radiolabeled Inorganic Nanomaterials

    Science.gov (United States)

    Sun, Xiaolian; Cai, Weibo; Chen, Xiaoyuan

    2015-01-01

    CONSPECTUS Positron emission tomography (PET) is a radionuclide imaging technology that plays an important role in preclinical and clinical research. With administration of a small amount of radiotracer, PET imaging can provide a noninvasive, highly sensitive, and quantitative readout of its organ/tissue targeting efficiency and pharmacokinetics. Various radiotracers have been designed to target specific molecular events. Compared with antibodies, proteins, peptides, and other biologically relevant molecules, nanoparticles represent a new frontier in molecular imaging probe design, enabling the attachment of different imaging modalities, targeting ligands, and therapeutic payloads in a single vector. We introduce the radiolabeled nanoparticle platforms that we and others have developed. Due to the fundamental differences in the various nanoparticles and radioisotopes, most radiolabeling methods are designed case-by-case. We focus on some general rules about selecting appropriate isotopes for given types of nanoparticles, as well as adjusting the labeling strategies according to specific applications. We classified these radiolabeling methods into four categories: (1) complexation reaction of radiometal ions with chelators via coordination chemistry; (2) direct bombardment of nanoparticles via hadronic projectiles; (3) synthesis of nanoparticles using a mixture of radioactive and nonradioactive precursors; (4) chelator-free postsynthetic radiolabeling. Method 1 is generally applicable to different nanomaterials as long as the surface chemistry is well-designed. However, the addition of chelators brings concerns of possible changes to the physicochemical properties of nanomaterials and detachment of the radiometal. Methods 2 and 3 have improved radiochemical stability. The applications are, however, limited by the possible damage to the nanocomponent caused by the proton beams (method 2) and harsh synthetic conditions (method 3). Method 4 is still in its infancy

  3. Radiolabeled antibody imaging in the management of colorectal cancer. Results of a multicenter clinical study

    International Nuclear Information System (INIS)

    Doerr, R.J.; Abdel-Nabi, H.; Krag, D.; Mitchell, E.

    1991-01-01

    Presurgical colorectal cancer patients (n = 116) received single intravenous infusions of 1 mg of CYT-103 (OncoScint CR103), an immunoconjugate of monoclonal antibody B72.3, radiolabeled with 111In. Following gamma camera imaging, 103 patients underwent an operative procedure: 92 had primary or recurrent colorectal carcinoma, 1 patient evaluated for recurrence of colorectal cancer had a second primary malignancy (small cell lung), and 10 patients had no demonstrable evidence of malignancy. 111In-CYT-103 immunoscintigraphic findings were consistent with the pathologic diagnoses for 70% of patients with colorectal cancer and 90% of disease-free patients. Antibody imaging contributed to surgical decision making through the detection of occult disease (12% of patients) and the confirmation of localized, potentially resectable disease without regional or metastatic spread. Seven patients (6%) experienced adverse effects, primarily fevers and itching, and 33% of patients developed antibodies to murine immunoglobulin after administration of 111In-CYT-103. The results of this study suggest that 111In-CYT-103 is a useful diagnostic tool for the presurgical evaluation of colorectal cancer patients

  4. Radiolabelled aptamers for tumour imaging and therapy

    International Nuclear Information System (INIS)

    Perkins, A.C.; Missailidis, S.

    2005-01-01

    Full text: The growth in biotechnology has led to new techniques for the design, selection and production of ligands capable of molecular recognition. One promising approach is the production of specific receptor binding molecules based on specific nucleic acid sequences that are capable of recognising a wide array of target molecules. These oligonuclide ligands are known as aptamers. The technology that allows production of aptamer molecules is known as systematic evolution of ligands by exponential enrichment (SELEX). We have used combinatorial chemistry techniques coupled with polymerase chain reaction (PCR) to rapidly select aptamers from degenerate libraries that bind with high affinity and specificity to the protein core of the MUC1 antigen, a tumour marker previously extensively used in tumour imaging and therapy. MUC1 is widely expressed by normal glandular epithelial cells, however this expression is dramatically increased when the cells become malignant. This has been well documented for breast and ovarian cancer, as well as some lung, pancreatic and prostate cancers. Recently it has also been shown that MUC1 is a valuable marker for bladder and has been used for the imaging and targeted therapy of bladder cancer. The aptamer selection process was performed on affinity chromatography matrices. After ten rounds of selection and amplification, aptamers were cloned and sequenced. Post SELEX amino modifications have been used to confer nuclease resistance and coupling potential. The aptamers bound to MUC1 antigen with a Kd of 5nm and high specificity, demonstrated by fluorescent microscopy on MUC1-expressing tumour cells. Using peptide coupling reactions, we have successfully attached chelators for Tc-99m radiolabelling. Two of the constructs tested were based on mono-aptamer chelator complexes, one with commercially available MAG3 and one with a novel designed cyclen-based chelator. The other two constructs were based on the use of multi-aptamer complexes

  5. Innovations that influence the pharmacology of monoclonal antibody guided tumor targeting

    International Nuclear Information System (INIS)

    Schlom, J.; Hand, P.H.; Greiner, J.W.; Colcher, D.; Shrivastav, S.; Carrasquillo, J.A.; Reynolds, J.C.; Larson, S.M.; Raubitschek, A.

    1990-01-01

    Tumor targeting by monoclonal antibodies (MAbs) can be enhanced by (a) increasing the percentage of injected dose taken up by the tumor and/or (b) increasing the tumor:nontumor ratios. Several groups have demonstrated that one can increase tumor to nontumor ratios by the use of antibody fragments or the administration of second antibodies. Several other modalities are also possible: (a) the use of recombinant interferons to up-regulate the expression of specific tumor associated antigens such as carcinoembryonic antigen or TAG-72 on the surface of carcinoma cells and thus increase MAb tumor binding has proved successful in both in vitro and in vivo studies; (b) the intracavitary administration of MAbs. Recent studies have demonstrated that when radiolabeled B72.3 is administered i.p. to patients with carcinoma of the peritoneal cavity, it localizes tumor masses with greater efficiency than does concurrent i.v. administered antibody. Studies involving the comparative pharmacology of intracavitary administration of radiolabeled MAb in patients and several animal models will be discussed; (c) it has been reported that prior exposure of hepatoma to external beam radiation will increase radiolabeled MAb tumor targeting. We and others have not been able to duplicate this phenomenon with a human colon cancer xenograft model and radiolabeled MAbs to two different colon carcinoma associated antigens. The possible reasons for these differences will be discussed; (d) the cloning and expression of recombinant MAbs with human constant regions and subsequent size modification constructs will also undoubtedly alter the pharmacology of MAb tumor binding in both diagnostic and therapeutic applications. 66 references

  6. 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

  7. Rhenium–platinum antitumor systems

    Directory of Open Access Journals (Sweden)

    A. V. Shtemenko

    2017-04-01

    Full Text Available This review provides an overlook of design (in short, antitumor and other biological activity of quadruple-bonded cluster dirhenium(III compounds and their synergism with cisplatin. In particular, we describe the work of the rhenium-platinum antitumor system (introduction of rhenium and platinum compounds. Among known metal-based anticancer drugs and drug candidates dirhenium(III compounds differ profoundly due to their strong antiradical and antioxidant properties determined by quadruple bond unsaturation. Such advantages of metal complexes as more expressed redox chemical propertie should be exploited for creating more efficient anticancer drugs. Combination of drugs leads to synergistic effects and/or to lowe­ring toxicity of platinides and is very promising in cancer chemotherapy. The review covers the follo­wing items: design of quadruple bonded dirhenium(III clusters, their spectral and antiradical properties (in short; interaction of the dirhenium(III compounds with lipids and formation of liposomes; interaction of the dirhenium(III compounds with erythrocytes and their antihemolytic activity in the models of hemolytic anemia; anticancer activity of dirhenium clusters and work of the rhenium-platinum antitumor system; antianemic and antioxidant properties of the dirhenium(III compounds in the model of tumor growth; interaction of the dirhenium(III compounds with nucleobases and DNA. Some modern trends in the field of bioinorganic and medicinal chemi­stry are also considered regarding their connection to the rhenium-platinum system efficiency: use of combinational therapy and nanomaterials; involvement of some biologically active ligands and redox-activation strategy, etc.

  8. DOTA-functionalized polylysine: a high number of DOTA chelates positively influences the biodistribution of enzymatic conjugated anti-tumor antibody chCE7agl.

    Science.gov (United States)

    Grünberg, Jürgen; Jeger, Simone; Sarko, Dikran; Dennler, Patrick; Zimmermann, Kurt; Mier, Walter; Schibli, Roger

    2013-01-01

    Site-specific enzymatic reactions with microbial transglutaminase (mTGase) lead to a homogenous species of immunoconjugates with a defined ligand/antibody ratio. In the present study, we have investigated the influence of different numbers of 1,4,7,10-tetraazacyclododecane-N-N'-N''-N'''-tetraacetic acid (DOTA) chelats coupled to a decalysine backbone on the in vivo behavior of the chimeric monoclonal anti-L1CAM antibody chCE7agl. The enzymatic conjugation of (DOTA)1-decalysine, (DOTA)3-decalysine or (DOTA)5-decalysine to the antibody heavy chain (via Gln295/297) gave rise to immunoconjugates containing two, six or ten DOTA moieties respectively. Radiolabeling of the immunoconjugates with (177)Lu yielded specific activities of approximately 70 MBq/mg, 400 MBq/mg and 700 MBq/mg with increasing numbers of DOTA chelates. Biodistribution experiments in SKOV3ip human ovarian cancer cell xenografts demonstrated a high and specific accumulation of radioactivity at the tumor site for all antibody derivatives with a maximal tumor accumulation of 43.6±4.3% ID/g at 24 h for chCE7agl-[(DOTA)-decalysine]2, 30.6±12.0% ID/g at 24 h for chCE7agl-[(DOTA)3-decalysine]2 and 49.9±3.1% ID/g at 48 h for chCE7agl-[(DOTA)5-decalysine)]2. The rapid elimination from the blood of chCE7agl-[(DOTA)-decalysine]2 (1.0±0.1% ID/g at 24 h) is associated with a high liver accumulation (23.2±4.6% ID/g at 24 h). This behavior changed depending on the numbers of DOTA moieties coupled to the decalysine peptide with a slower blood clearance (5.1±1.0 (DOTA)3 versus 11.7±1.4% ID/g (DOTA)5, pDOTA)3 versus 5.8±0.7 (DOTA)5, pDOTA-substituted decalysine ((DOTA)5-decalysine) to an anti-tumor antibody leads to the formation of immunoconjugates with high specific activity and excellent in vivo behavior and is a valuable option for radioimmunotherapy and potentially antibody-drug conjugates (ADCs).

  9. DOTA-functionalized polylysine: a high number of DOTA chelates positively influences the biodistribution of enzymatic conjugated anti-tumor antibody chCE7agl.

    Directory of Open Access Journals (Sweden)

    Jürgen Grünberg

    Full Text Available Site-specific enzymatic reactions with microbial transglutaminase (mTGase lead to a homogenous species of immunoconjugates with a defined ligand/antibody ratio. In the present study, we have investigated the influence of different numbers of 1,4,7,10-tetraazacyclododecane-N-N'-N''-N'''-tetraacetic acid (DOTA chelats coupled to a decalysine backbone on the in vivo behavior of the chimeric monoclonal anti-L1CAM antibody chCE7agl. The enzymatic conjugation of (DOTA1-decalysine, (DOTA3-decalysine or (DOTA5-decalysine to the antibody heavy chain (via Gln295/297 gave rise to immunoconjugates containing two, six or ten DOTA moieties respectively. Radiolabeling of the immunoconjugates with (177Lu yielded specific activities of approximately 70 MBq/mg, 400 MBq/mg and 700 MBq/mg with increasing numbers of DOTA chelates. Biodistribution experiments in SKOV3ip human ovarian cancer cell xenografts demonstrated a high and specific accumulation of radioactivity at the tumor site for all antibody derivatives with a maximal tumor accumulation of 43.6±4.3% ID/g at 24 h for chCE7agl-[(DOTA-decalysine]2, 30.6±12.0% ID/g at 24 h for chCE7agl-[(DOTA3-decalysine]2 and 49.9±3.1% ID/g at 48 h for chCE7agl-[(DOTA5-decalysine]2. The rapid elimination from the blood of chCE7agl-[(DOTA-decalysine]2 (1.0±0.1% ID/g at 24 h is associated with a high liver accumulation (23.2±4.6% ID/g at 24 h. This behavior changed depending on the numbers of DOTA moieties coupled to the decalysine peptide with a slower blood clearance (5.1±1.0 (DOTA3 versus 11.7±1.4% ID/g (DOTA5, p<0.005 at 24 h and lower radioactivity levels in the liver (21.4±3.4 (DOTA3 versus 5.8±0.7 (DOTA5, p<0.005 at 24 h. We conclude that the site-specific and stoichiometric uniform conjugation of the highly DOTA-substituted decalysine ((DOTA5-decalysine to an anti-tumor antibody leads to the formation of immunoconjugates with high specific activity and excellent in vivo behavior and is a valuable option for

  10. Recent progress of diagnostic and therapeutic approach to cancers using polyclonal or monoclonal antibodies

    International Nuclear Information System (INIS)

    Koji, Toshihiko

    1982-01-01

    Among the major topics of interest in cancer immunology, immunodiagnosis and immunotherapy with the antibodies are summarized historically and prospectively. The concept of injecting anti-tumor cell antibodies to localize tumors was first introduced in experimental systems by Pressman (1957). Since then, various trials have been achieved with human tumors using specific or nonspecific tumor-localizing antibodies diagnostically or therapeutically. In 1970's, successes in immunodiagnosis with the antibodies to oncofetal proteins also have been reported. Recently, there are numerous papers dealed with a series of external scanning or serotherapeutic trials by the use of monoclonal antibodies that bind selectively to tumor cells. Various relevant problems with them are discussed. (author)

  11. Clearance of 131I-labeled murine monoclonal antibody from patients' blood by intravenous human anti-murine immunoglobulin antibody

    International Nuclear Information System (INIS)

    Stewart, J.S.; Sivolapenko, G.B.; Hird, V.; Davies, K.A.; Walport, M.; Ritter, M.A.; Epenetos, A.A.

    1990-01-01

    Five patients treated with intraperitoneal 131I-labeled mouse monoclonal antibody for ovarian cancer also received i.v. exogenous polyclonal human anti-murine immunoglobulin antibody. The pharmacokinetics of 131I-labeled monoclonal antibody in these patients were compared with those of 28 other patients receiving i.p.-radiolabeled monoclonal antibody for the first time without exogenous human anti-murine immunoglobulin, and who had no preexisting endogenous human anti-murine immunoglobulin antibody. Patients receiving i.v. human anti-murine immunoglobulin antibody demonstrated a rapid clearance of 131I-labeled monoclonal antibody from their circulation. The (mean) maximum 131I blood content was 11.4% of the injected activity in patients receiving human anti-murine immunoglobulin antibody compared to 23.3% in patients not given human anti-murine immunoglobulin antibody. Intravenous human anti-murine immunoglobulin antibody decreased the radiation dose to bone marrow (from 131I-labeled monoclonal antibody in the vascular compartment) 4-fold. Following the injection of human anti-murine immunoglobulin antibody, 131I-monoclonal/human anti-murine immunoglobulin antibody immune complexes were rapidly transported to the liver. Antibody dehalogenation in the liver was rapid, with 87% of the injected 131I excreted in 5 days. Despite the efficient hepatic uptake of immune complexes, dehalogenation of monoclonal antibody was so rapid that the radiation dose to liver parenchyma from circulating 131I was decreased 4-fold rather than increased. All patients developed endogenous human anti-murine immunoglobulin antibody 2 to 3 weeks after treatment

  12. Iodogen-mediated radiolabeling of Bevacizumab with I-123 for clinical applications

    International Nuclear Information System (INIS)

    Lemps, R. de; Desruet, M.; Bacot, S.; Ahmadi, M.; Ghezzi, C.; Desruet, M.; Fagret, D.; Berger, F.

    2014-01-01

    Bevacizumab is a monoclonal antibody, directed against vascular endothelial growth factor (VEGF), and is currently used in various types of cancers (breast, lung, colorectal). In order to administer to humans glioblastomas, we developed its iodine 123 radiolabeling for in vitro and in vivo studies subsequent. The aim of the study is to choose the best radioiodination conditions based on feasibility in a hospital radiopharmacy: Quick one step method under mild condition, reproducible, using materials for pharmaceutical use and in a closed-system. Method Bevacizumab was radiolabeled with "1"2"3I using Iodogen, the most widely used oxidants in direct labelling techniques for tyrosyl residues-containing compounds. We have been explored two crucial parameters for clinical transfer: the amount of oxidant required (50μg and 100μg) and the choice of the purification column (size exclusion column or anion exchange resin), respectively. Quality control was performed before and after purification of each condition in order to evaluate the radiochemical purity (RCP) and purification efficiency. The stability of the radiolabeled molecule is evaluated over time and also when the solution is diluted with unlabeled bevacizumab. Moreover, the in vitro stability of "1"2"3I-bevacizumab was determined in presence of human blood at 15, 30, 60 and 120 min. Labeling yield before purification was 96.5% for the first condition (50μg Iodogen) and 95.5% for the second one (100μg Iodogen). The radiochemical purity was 99.5% after purification on a size exclusion column and 99% after purification on anion exchange resin. The purification yield with size exclusion column is 75%, compared with 81% of the anionic exchange resin. The stability in the labeling medium of "1"2"3I-bevacizumab at 3, 6, 24 and 30 h after labeling showed a RCP at 100%, 93%, 99.8% and 99.8% for condition 1 so that it was found to be 99.2%, 100%, 99.3%, 99.5% for condition 2, respectively. In vitro incubation with

  13. Radiolabeling as a tool to study uptake pathways in plants

    Energy Technology Data Exchange (ETDEWEB)

    Schymura, Stefan; Hildebrand, Heike; Franke, Karsten [Helmholtz-Zentrum Dresden-Rossendorf e.V., Dresden (Germany). Reactive Transport; Fricke, T. [Vita34 BioPlanta, Leipzig (Germany)

    2017-06-01

    The identification of major uptake pathways in plants is an important factor when evaluation the fate of manufactured nanoparticles in the environment and the associated risks. Using different radiolabeling techniques we were able to show a predominantly particulate uptake for CeO{sub 2} nanoparticles (NPs) in contrast to a possible uptake in the form of ionic cerium.

  14. Current status and future developments in radiolabelled immunoassays

    International Nuclear Information System (INIS)

    Edwards, R.

    1998-01-01

    Radioisotopes are used extensively in medical practice and their use in RIA or IRMA usually represent a small proportion of the total. Radiolabelled immunoassays based on 125 I constitute a simple didactic, cost effective and robust technology which is still regarded as the reference method in many clinical applications. The IAEA has implemented many successful programmes using the ''bulk reagent'' approach, involving 68 countries in all the different regions. The main achievements have been in technology transfer with self sufficiency in production for some countries; training of large numbers of staff; quality control and quality assurance schemes; devolution of screening programmes for neonatal congenital hypothryoidism. Alternatives to the use of radioisotopic tracers are constrained by many factors and are often only available in restricted commercial packages. They are often not suitable for technology transfer programmes and often lack any didactic component in addition to a relative high cost. The production of radiolabels using 125 I is both simple and adaptable. In addition expertise in their preparation and purification is widespread even in developing countries. Together with the ease of producing antibodies, the facts have made 125 I-radiolabelled immunoassays ideal for investigative procedures for many research activities (30,31) particularly in the medical context where radioisotopes are commonly used. In conclusion, even a superficial examination of public health statistics for various countries throughout the continents indicates a need for a simple, inexpensive and robust analytical tool. In this light, there is a predicted continuing role for radiolabelled immunoassays. (author)

  15. Synthesis of sup 14 C-radiolabelled Tilmicosin

    Energy Technology Data Exchange (ETDEWEB)

    Crouse, G D; Terando, N H [Lilly (Eli) and Co., Indianapolis, IN (USA). Lilly Research Labs.

    1989-04-01

    Tilmicosin was radiolabelled with carbon-14 on the 3,5-dimethylpiperidinyl sidechain as a requirement for animal metabolism studies. A new radiosynthesis of 3,5-dimethyl-piperidine was developed for this purpose. Incorporation into the desmycosin nucleus was accomplished by a reductive amination reaction. (author).

  16. A novel method of 18F radiolabeling for PET.

    NARCIS (Netherlands)

    McBride, W.J.; Sharkey, R.M.; Karacay, H.; D'Souza, C.A.; Rossi, E.A.; Laverman, P.; Chang, C.H.; Boerman, O.C.; Goldenberg, D.M.

    2009-01-01

    Small biomolecules are typically radiolabeled with (18)F by binding it to a carbon atom, a process that usually is designed uniquely for each new molecule and requires several steps and hours to produce. We report a facile method wherein (18)F is first attached to aluminum as Al(18)F, which is then

  17. Radiolabeled antibodies and RGD-peptides for the treatment of ovarian cancer.

    NARCIS (Netherlands)

    Janssen, M.L.H.

    2004-01-01

    In this thesis, preclinical studies on new treatment modalities for ovarian cancer are descibed, applying radiolabeled antibodies and radiolabeled RGD-peptides. In chapter 2 a study is described comparing the therapeutic efficacy of the antibody HMFG1 radiolabeled with several beta-emitting

  18. Development of Radiolabeled compounds using reactor-produced radionuclides

    International Nuclear Information System (INIS)

    Choi, Sun Ju; Park, K. B.; Park, S. H.

    2007-06-01

    To establish a robust technology for radiopharmaceutical development, we focused on the configuration of fundamental development of radiolabeled compounds for radioimmunotherapy and drug delivery as well as the development of bifunctional chelating agents and radiolabeling methods for the radiopharmaceuticals with highly specific activity to deliver sufficient number of radionuclides to the target site. In this project, we aim to improve the quality of life and the public welfare by fostering the medical application of radioisotopes for the effective treatment of malignant diseases and by developing efficient radiolabeling methods of specific bio-active materials with radioisotopes and new candidates for radiopharmaceutical application. We have established the procedure for the preparation of radiolabeled antibody and biotin with radioisotopes such as 166 Ho, 131 I, 90 Y and 111 In for tumour targeting. In the future, these technologies will be applicable to development of radioimmunotherapeutic drug. The combination treatment of radioisotope with anti-cancer agents or chemotherapeutic agents may produce a synergistic static effects in the tumour and this synergism would be exerted via gene level through the activation of a cell death pathway. The combination therapy may be very beneficial for cancer treatment and this can overcome not only the hazards of unnecessary exposure to high radiation level during therapy, but also the tendency for drug resistance caused by chemotherapy. To develop new drug delivery system suitable for CT imaging agent, a chitosan derivative and radiolabed Folate-targeted polymer with 131 I were synthesized. We also carried out the development of DTPA derivatives for CT imaging agent, radiolabeled precursor, and established a highly efficient radiolabeling methodology with lanthanide nuclide. In order to develop neuroreceptor targeting compounds, we synthesized WAY-100635 compound and 99m Tc(CO) 3 precursor from Chrysamine G derivatives

  19. Radioimmunoimaging in malignant melanoma with 111In-labeled monoclonal antibody 96.5

    International Nuclear Information System (INIS)

    Murray, J.L.; Rosenblum, M.G.; Sobol, R.E.

    1985-01-01

    A radiolabeled monoclonal antibody (96.5) reactive with an Mr 97,000 antigen found on over 80% of melanoma cell lines and tissue extracts was examined for its ability to detect malignant melanoma metastases in vivo. For imaging purposes, it was conjugated with diethyltriaminepentaacetic acid and subsequently labeled with 111 In by chelation. Thirty-one patients with metastatic melanoma received single injections of monoclonal antibody 96.5 at concentrations ranging from 0.5 to 20 mg and at specific activities of 111 In ranging from 0.125 to 4 mCi/mg. Total-body scans were performed at various time intervals following administration. No serious side effects were observed. Of a total of 100 previously documented metastatic sites, 50 imaged for a specificity of 50%. The number of sites imaged increased significantly as the amount of antibody administered increased relative to the average radiation dose. Considerable background uptake of isotope was observed in blood pool and other organs with gradual acquisition of label in tumor sites by 48 to 72 h. Hence, tumor imaging of melanoma using 111 In-labeled monoclonal antibody 96.5 appeared feasible, especially at antibody doses above 2 mg

  20. 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

  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. 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...

  3. Antitumoral activity of marine organism

    International Nuclear Information System (INIS)

    Valdes Iglesias, O; Perez Gil, R; Colom, Y

    2010-01-01

    The study of the natural products from marine organism constitute a relatively recent scientific researcher field with high potentialities tanking in consideration that the oceans cover the three of the four parts of the earth. Poryphera and Bryozoans have been the Phylum more studied owning to the vulnerability, their soft body, their habitat on rocks, their slow movement and bright colors, for these reason these organisms are able to produce chemical substances as defense methods against depredators. Same mechanism is exhibit by the seaweeds with the production of secondary metabolites . In the present communication are exposed the main results obtained on the world a Cuba until the present in the looking for of substances with antitumor action from marine organism

  4. Antitumor effects of radioiodinated antisense oligonucleotide mediated by VIP receptor

    International Nuclear Information System (INIS)

    Ou Xiaohong; Tan Tianzhi; Li Yunchun; Kuang Anren

    2004-01-01

    Purpose: we had constructed a targeting delivery system based on intestinal peptide (VIP) for antisense oligonucleotide (ASON) transfer into VIP receptor-positive cells in previous study. The aims of present studies are to observe the antitumor effect of VIP-131I-ASON in HT29 human colon adenocarcinoma xenografts. Methods: A 15-met phosphorothioate ASON, which was complementary to the translation start region of the C-myc oncogene mRNA, was labeled with 131I and the labelled compound was linked to the VIP bound covalently 'to a polylysine chain so as to deliver oligonucleotide into tumor cells. Distribution experiments for evaluating the radiolabeled antisense complexe uptake in tumor tissue were performed in BALB/c nude mice bearing with HT29 tumor xenografts. Nude mice beating HT29 tumor xenografts were adminstered VIP-131I-ASON (3.7,7.4 MBq) or 131I-ASON (3.7 MBq), 131I labeled control sense and nosense DNA (3.7 MBq), or saline. Antitumor effects were assessed using endpoints of tumor growth delay. C-myc-encoded protein expression of tumor was measured by immunocytohistochemical staining. Results: Distribution experiment performed with athymic mice bearing human colon tumor xenografts revealed maximal accumulation of conjugated ASON in the tumor tissue 2 h after administration and significantly higher than that in nude mice injected unconjngated ASON [(5.89±1.03)%ID/g and(1.56±0.31)%ID/g, respectively; t=7.7954 P<0.001]. The radioratio of tumor to muscle was peaked 4h after administration. VIP-131I-ASON exhibited strong antitumor effects against HT29 xenografts, decreasing their growth rate 7-fold compare with that in saline-treated mice(tumor growth delay, 25.4±0.89 day). The antitumor effects of unconjugated 131I-ASON were much less profound than VIP-131I-ASON (tumor growth delay, 3.2±1.3 and 25.4±0.89 day, respectively; q=51.4126 P<0.01). Sense, nosense control ON with VIP carder caused no therapeutic effect. There was no progressive weight loss or

  5. 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.

  6. Method for radiolabeling proteins with technetium-99m

    International Nuclear Information System (INIS)

    Crockford, D.R.; Rhodes, B.A.

    1984-01-01

    In accordance with this invention, a substrate to be radiolabeled with technetium-99m is admixed with a buffered stannous chloride composition having a pH between about 4.5 and about 8.5 wherein the stannous chloride is produced from a non-oxidized tin source, the buffered stannous chloride is purged of oxygen and the buffer comprises a mixture of alkali metal biphthalate and an alkali metal tartrate. Alternatively, the buffer may include alkali metal borate or gentisate. The stannous chloride solution is admixed with the buffer and the resultant mixture is neutralized with sodium hydroxide. The neutralized solution then is admixed with the substrate eventually to be radiolabeled with technetium-99m. This solution is allowed to incubate for several hours (usually over 15 hours) in the absence of oxygen and at room temperature

  7. Quantitation of radiolabeled compounds eluting from the HPLC system

    International Nuclear Information System (INIS)

    Kessler, M.J.

    1982-01-01

    Three techniques are compared for the quantitation of various radiolabeled compounds eluting in the high performance liquid chromatography system. The first technique requires fraction-collecting the effluent from the HPLC, removing an aliquot to scintillation vials, and counting each fraction in a liquid scintillation counter. The second uses direct interface of the HPLC effluent to a flow-through radioactivity detector. The third involves quantitation of various radiolabeled compounds (proteins, steroids, and nucleotides) by splitting the effluent from the HPLC with an electronic steam splitter, thus diverting a present portion to the fraction collector for further chemical characterization and the remainder to the radioactivity flow detector for direct quantitation. A direct comparison of the chromatograms and the radioactivity counting efficiencies of these three techniques is presented

  8. Radiolabeled microsphere measurements of alveolar bone blood flow in dogs

    International Nuclear Information System (INIS)

    Kaplan, M.L.; Jeffcoat, M.K.; Goldhaber, P.

    1978-01-01

    Radiolabeled microspheres were injected into the left cardiac ventricle in healthy adult dogs to quantify blood in maxillary and mandibular alveolar bone. Heart rate, arterial blood pressure and pulse contour were monitored throughout each experiment. Blood flow in maxillary alveolar bone was more than 30 % greater (p<.001) than in mandibular alveolar bone. Alveolar bone blood flow (mean +- S.D.) measured as ml/min per gram was 0.12 +- .02 in the maxilla compared to 0.09 +- .02 in the mandible. The cardiovascular parameters monitored were constant immediately prior to the injection of microspheres and remained unchanged during and following injection. It is possible that radiolabeled microspheres can be used to quantify the circulatory changes in alveolar bone during the development of destructive periodontal disease in dogs. (author)

  9. Development of a new radiolabel (lead-203) and new chelating agents for labeling monoclonal anntibodies for imaging

    International Nuclear Information System (INIS)

    Srivastava, S.C.; Mease, R.C.; Meinken, G.E.; Mausner, L.F.; Steplewski, Z.

    1988-01-01

    High liver uptake and slow body clearance presently limit the usefulness of 111 In labeled antibodies for tumor imaging. We have investigated 203 Pb as an alternate and better antibody label. The DTPA and cyclohexyl EDTA (CDTA) conjugates of an anticolon carcinoma antibody, 17-1A were labeled (bicyclic anhydride method) with 203 Pb and 111 In with 60 and 90% labeling yields, respectively. The biodistribution of 203 Pb-17-1A conjugates was compared with the corresponding 111 In-labeled preparations and with 203 Pb-DTPA, 203 Pb-nitrate and nonrelevant antibody controls in normal and human tumor (SW948) xenografted nude mice at 24, and 96 hr. Lead-203-labeled CDTA and DTPA antibody conjugates gave similar in vivo distributions. Even though the lead bound to these chelate-antibody conjugates was more labile in serum and in vivo, compared to indium, it cleared much faster from the liver and the whole body. A new series of chelating agents based on the incorporation of a trans-1,2- diaminocyclohexane moiety into the carbon backbone of polyaminocarboxylates is being synthesized. These are expected to provide stronger complexing ability for lead and produce greater in vivo stability. These ligands are also expected to be superior to EDTA and DTPA for labeling antibodies with other radiometals, including indium. 32 refs., 3 tabs

  10. Radiolabeled Monoclonal Antibody and Combination Chemotherapy Before Stem Cell Transplant in Treating Patients With High-Risk Lymphoid Malignancies

    Science.gov (United States)

    2017-08-23

    Recurrent B-Cell Non-Hodgkin Lymphoma; Recurrent Hodgkin Lymphoma; Recurrent Mantle Cell Lymphoma; Recurrent T-Cell Non-Hodgkin Lymphoma; Refractory B-Cell Non-Hodgkin Lymphoma; Refractory Hodgkin Lymphoma; Refractory Mantle Cell Lymphoma; Refractory T-Cell Non-Hodgkin Lymphoma

  11. Localisation and mechanism of renal retention of radiolabelled somatostatin analogues

    Energy Technology Data Exchange (ETDEWEB)

    Melis, Marleen; Krenning, Eric P.; Bernard, Bert F.; Jong, Marion de [Erasmus MC, Department of Nuclear Medicine, Rotterdam (Netherlands); Barone, Raffaella [UCL, Centre of Nuclear Medicine and Laboratory of PET, Brussels (Belgium); Visser, Theo J. [Erasmus MC, Department of Internal Medicine, Rotterdam (Netherlands)

    2005-10-01

    Radiolabelled somatostatin analogues, such as octreotide and octreotate, are used for tumour scintigraphy and radionuclide therapy. The kidney is the most important critical organ during such therapy owing to the reabsorption and retention of radiolabelled peptides. The aim of this study was to investigate in a rat model both the localisation and the mechanism of renal uptake after intravenous injection of radiolabelled somatostatin analogues. The multi-ligand megalin/cubilin receptor complex, responsible for reabsorption of many peptides and proteins in the kidney, is an interesting candidate for renal endocytosis of these peptide analogues. For localisation studies, ex vivo autoradiography and micro-autoradiography of rat kidneys were performed 1-24 h after injection of radiolabelled somatostatin analogues and compared with the renal anti-megalin immunohistochemical staining pattern. To confirm a role of megalin in the mechanism of renal retention of [{sup 111}In-DTPA]octreotide, the effects of three inhibitory substances were explored in rats. Renal ex vivo autoradiography showed high cortical radioactivity and lower radioactivity in the outer medulla. The distribution of cortical radioactivity was inhomogeneous. Micro-autoradiography indicated that radioactivity was only retained in the proximal tubules. The anti-megalin immunohistochemical staining pattern showed a strong similarity with the renal [{sup 111}In-DTPA]octreotide ex vivo autoradiograms. Biodistribution studies showed that co-injection of positively charged d-lysine reduced renal uptake to 60% of control. Sodium maleate reduced renal [{sup 111}In-DTPA]octreotide uptake to 15% of control. Finally, cisplatin pre-treatment of rats reduced kidney uptake to 70% of control. Renal retention of [{sup 111}In-DTPA]octreotide is confined to proximal tubules in the rat kidney, in which megalin-mediated endocytosis may play an important part. (orig.)

  12. Novel strategies for microdose studies using non-radiolabeled compounds.

    Science.gov (United States)

    Maeda, Kazuya; Sugiyama, Yuichi

    2011-06-19

    Microdose studies using non-radiolabeled compounds enable assessment of the clinical pharmacokinetics of drug candidates in humans without the need to synthesize radiolabeled compounds. We have demonstrated that the quantification limits of many drugs measured by LC-MS/MS are low enough to allow estimation of their pharmacokinetic parameters following administration of a microdose. Our previous microdose studies with LC-MS/MS demonstrated the linear pharmacokinetics of fexofenadine between microdoses and therapeutic doses. We also obtained time profiles of plasma concentrations of nicardipine and its multiple metabolites following administration of a microdose. A significant advantage of using non-radiolabeled compounds is the ability to perform cassette microdose studies. By administering multiple drug candidates to the same subject, we can select compounds with appropriate pharmacokinetic properties simultaneously. We can also clarify major factors dominating the pharmacokinetics of drug candidates by cocktail microdosing of the test compounds and probe substrates with or without specific inhibitors for enzymes/transporters. Copyright © 2011 Elsevier B.V. All rights reserved.

  13. Radiolabelling of autologous leucocytes: technique and clinical application

    International Nuclear Information System (INIS)

    Strobl-Jaeger, E.; Kolbe, H.; Ludwig, H.; Sinzinger, H.

    1988-01-01

    Gamma-camera imaging after injection of radiolabelled autologous leucocytes can be very helpful in the diagnosis, localization and further clinical treatment of inflammatory diseases. We present a technique allowing sterile separation of white blood cells and labelling with 99m Tc-phytate or -oxine and with 111 In-oxine, -oxine sulphate or -tropolone. The method is non-invasive and the radiation dose amounts to less than 80 mrad using 100 μCi 111 Indium. The use of radiolabelled granulocytes is of particular diagnostic value in patients with septicaemia of unknown origin. Whole body scanning allows not only visualization of enhanced splenic uptake in septicaemia, but also localization of an inflammatory process. Preferential indications for a diagnostic approach using radiolabelled granulocytes are inflammatory abdominal processes which cannot easily be documented by means of other non-invasive techniques, such as inflammatory bowel disease (Crohn's diseases and ulcerative colitis), arthritic processes and abscesses of the liver and spleen, as well as subphrenic and retroperitoneal abscesses. Untreated osteomyelitis can be located with the help of labelled granulocytes, but in patients treated with antibiotics a false negative result is obtained in approximately 50 % of cases for as yet unknown reasons, even in the presence of a still active osteomyelitic process. (Authors)

  14. Radiolabeling, biodistribution and tumor imaging of stealth liposomes containing methotrexate

    International Nuclear Information System (INIS)

    Subramanian, N; Arulsudar, N; Chuttani, K; Mishra, P; Sharma, R.K; Murthy, R.S.R

    2003-01-01

    To study the utility of sterically stabilized liposomes (stealth liposomes) in tumor scintigraphy by studying its biodistribution and accumulation in target tissue after radiolabeling with Technetium-99m (99mTC). Conventional and Stealth liposomes were prepared by lipid film hydration method using methotrexate as model anticancer drug. Radiolabeling of the liposomes was carried out by direct labeling using reduced 99mTc. Experimental conditions for maximum labeling yield were optimized. The stability studies were carried out to check binding strength of the radiolabeled complexes. The blood kinetic study was carried out in rabbits after giving the labeled complex by intravenous administration through ear vein. The biodistribution studies were carried out in the Ehrlich ascites tumor (EAT) bearing mice after intravenous administration through tail vein, showed prolonged circulation in blood and significant increase in the accumulation in tumor for the sterically stabilized liposomes compared to the conventional liposomes. The gamma scintigraphic image shows the distribution of the stealth liposomes in liver, spleen, kidney and tumor. The study gives precise idea about the use of stealth liposomes in tumor scintigraphy and organ distribution studies (Au)

  15. Monoclonal antibodies to DNA modified with cis- or trans-diamminedichloroplatinum(II)

    International Nuclear Information System (INIS)

    Sundquist, W.I.; Lippard, S.J.; Stollar, B.D.

    1987-01-01

    Murine monoclonal antibodies that bind selectively to adducts formed on DNA by the antitumor drug cis-diamminedichloroplatinum(II), cis-DDP, or to the chemothrapeutically inactive trans isomer trans-DDP were elicited by immunization with calf thymus DNA modified with either cis- or trans-DDP at ratios of bound platinum per nucleotide, (D/N)/sub b/, of 0.06-0.08. The binding of two monoclonal antibodies to cis-DDP-modified DNA was competitively inhibited in an enzyme-linked immunosorbent assay (ELISA) by 4-6 nM concentrations of cis-DDP bound to DNA. Adducts formed by cis-DDP on other synthetic DNA polymers did not inhibit antibody binding to cis-DDP-DNA. The biologically active compounds [Pt(en)Cl 2 ], [Pt(dach)Cl 2 ], and [Pt(NH 3 ) 2 (cbdca)] (carboplatin) all formed antibody-detectable adducts on DNA, whereas the inactive platinum complexes trans-DDP and [Pt(dien)Cl]Cl (dien, diethylenetriamine) did not. The monoclonal antibodies therefore recognize a bifunctional Pt-DNA adduct with cis stereochemistry in which platinum is coordinated by two adjacent guanines or, to a lesser degree, by adjacent adenine and guanine. A monoclonal antibody raised against trans-DDP-DNA was competitively inhibited in an ELISA by 40 nM trans-DDP bound to DNA. This antibody crossreacted with unmodified, denatured DNA. The recognition of cis- or trans-DDP-modified DNAs by monoclonal antibodies thus parallels the known modes of DNA binding of these compounds and may correlate with their biological activities

  16. Radioimmunodetection of hepatocellular carcinoma with a radiolabeled antibody to alpha fetoprotein

    Energy Technology Data Exchange (ETDEWEB)

    Ishii, N; Nakata, K; Muro, T [Nagasaki Univ. (Japan). School of Medicine

    1982-03-01

    The present study was undertaken to investigate whether or not radiolabeled antibody to Alpha-fetoprotein (AFP) intravenously administered accumulates in AFP-producing tumors. Rats with subcutaneously transplanted hepatoma or with heptoma produced in liver by 3'-Me-DAB, and 12 patients with hepatocellular carcinoma (HCC) were studied. In animal experiments, the tumor localization was clearly demonstrated by total body scintigraphy 48 to 168 hours after the injection of the radioiodinated antibody. The rats were sacrificed and radioactivity in tissues was counted. Tumor tissues showed the highest counts. In patients with HCC, the imaging was made with a gamma camera usually 24 and 48 hours after injection of I-131-labeled antibody. In order to make the contrast of tumor image clear, nonspecific background images obtained by administration of Tc-99m-labeled serum albumin were subtracted from the images obtained by I-131 labeled antibody with a computer. In 6 of 12 patients with HCC, the tumor location could successfully demonstrated. However, tumor with sizes below 2 cm in diameter which were able to be detected by the celiac angiography were not detectable. Interestingly the images were more clear in patients with relatively higher serum AFP levels. In the blood of patient given injection of AFP radioantibody, both immune complex and free antibody were able to be detected at least for 120 hours so that the presence of free antigen (AFP) did not appear to prevent tumor radioimmunodetection. The information obtained concerning the biochemical factors which influence antibody localization in the tumor would provide better method for radioimmunodetection with antitumor antibodies.

  17. Radioimmunodetection of hepatocellular carcinoma with a radiolabeled antibody to alpha fetoprotein

    International Nuclear Information System (INIS)

    Ishii, Nobuko; Nakata, Keisuke; Muro, Toyokichi

    1982-01-01

    The present study was undertaken to investigate whether or not radiolabeled antibody to Alpha-fetoprotein (AFP) intravenously administered is accumulate in AFP-producing tumors. Rats with subcutaneously transplanted hepatoma or with heptoma produced in liver by 3'-Me-DAB, and 12 patients with hepatocellular carcinoma (HCC) were studied. In animal experiments, the tumor localization was clearly demonstrated by total body scintigraphy 48 to 168 hours after the injection of the radioiodinated antibody. The rats were sacrificed and radioactivity in tissues was counted. Tumor tissues showed the highest counts. In patients with HCC, the imaging was made with a gamma camera usually 24 and 48 hours after injection of I-131-labeled antibody. In order to make the contrast of tumor image clear, nonspecific background images obtained by administration of Tc-99m-labeled serum albumin were subtracted from the images obtained by I-131 labeled antibody with a computer. In 6 of 12 patients with HCC, the tumor location could successfully demonstrated. However, tumor with sizes below 2 cm in diameter which were able to be detected by the celiac angiography were not detectable. Interes tingly the images were more clear in patients with relatively higher serum AFP levels. In the blood of patient given injection of AFP radioantibody, both immune complex and free antibody were able to be detected at least for 120 hours so that the presence of free antigen (AFP) did not appear to prevent tumor radioimmunodetection. The information obtained concerning the biochemical factors which influence antibody localization in the tumor would provide better method for radioimmunodetection with antitumor antibodies. (author)

  18. 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)

  19. Topographic antigenic determinants recognized by monoclonal antibodies on human choriogonadotropin beta-subunit

    International Nuclear Information System (INIS)

    Bidart, J.M.; Troalen, F.; Salesse, R.; Bousfield, G.R.; Bohuon, C.J.; Bellet, D.H.

    1987-01-01

    We describe a first attempt to study the antibody-combining sites recognized by monoclonal antibodies raised against the beta-subunit of human choriogonadotropin (hCG). Two groups of antibodies were first defined by their ability to recognize only the free beta-subunit or the free and combined subunit. Antibodies FBT-11 and FBT-11-L bind only to hCG beta-subunit but not to hCG, whereas antibodies FBT-10 and D1E8 bind to both the beta-subunit and the hormone. In both cases, the antigenic determinants were localized to the core of the protein (residues 1-112), indicating the weak immunogenicity of the specific carboxyl-terminal extension of hCG-beta. Nine synthetic peptides spanning different regions of hCG-beta and lutropin-beta were assessed for their capacity to inhibit antibody binding. A synthetic peptide inclusive of the NH2-terminal region (residues 1-7) of the hCG beta-subunit was found to inhibit binding to the radiolabeled subunit of a monoclonal antibody specific for free hCG-beta (FBT-11). Further delineation of the antigenic site recognized by this antibody provided evidence for the involvement of fragment 82-92. Moreover, monoclonal antibody FBT-11 inhibited the recombination of hCG-beta to hCG-alpha, indicating that its antigenic determinant might be located nearby or in the hCG-beta portion interacting with the alpha-subunit. Binding of monoclonal antibody FBT-10, corresponding to the second antigenic determinant, was weakly inhibited by fragment 82-105 and did not impair the recombination of the hCG beta-subunit to the hCG alpha-subunit. Its combining site appeared to be located in a region of the intact native choriogonadotropin present at the surface of the hormone-receptor complex

  20. 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.

  1. Novel approaches to cancer targeting using epitope-binding properties that mimic monoclonal antibodies

    International Nuclear Information System (INIS)

    1998-01-01

    The investigators have extensive experience in all of the techniques required for this project including: animal models of tumors, quantitative autoradiography, radiochemistry, peptide synthesis, organic synthesis, molecular biology, kinetic modeling and radionuclide imaging both with single photon and PET agents. Preliminary results and progress in the following areas are presented: (1) Establishment of an in vivo tumor model and successful targeting of this tumor using monoclonal antibodies raised to p185 erbB2 , (2a) Screening of a synthetic peptide combinatorial library, (2b) Screening of a phage display peptide library, (3) Determination of the epitope recognized by ICR12, (4) Radiolabeling with 99m Tc, 18 F and * I (radioiodines), (5) High resolution positron emission tomography (PET) studies of tumors, and (6) Development of a high resolution (∼mm) PET camera

  2. Radioimmunoguided surgery using the monoclonal antibody B72.3 in colorectal tumors

    International Nuclear Information System (INIS)

    Sickle-Santanello, B.J.; O'Dwyer, P.J.; Mojzisik, C.

    1987-01-01

    The authors have developed a hand-held gamma-detecting probe (GDP) for intraoperative use that improves the sensitivity of external radioimmunodetection. Radiolabeled monoclonal antibody (MAb) B72.3 was injected in six patients with primary colorectal cancer and 31 patients with recurrent colorectal cancer an average of 16 days preoperatively. The GDP localized the MAb B72.3 in 83 percent of sites. The technique, known as a radioimmunoguided surgery (RIGS) system did not alter the surgical procedure in patients with primary colorectal cancer but did alter the approach in 26 percent (8/31) of patients with recurrent colorectal cancer. Two patients avoided unnecessary liver resections and two underwent extraabdominal approaches to document their disease. The RIGS system may influence the short-term morbidity and mortality of surgery for colorectal cancer. Larger series and longer follow-up are needed to determine whether the RIGS system confers a survival advantage to the patient with colorectal cancer

  3. 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.).

  4. 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.)

  5. Use of radiolabeled antibodies as diagnostic imaging agents

    International Nuclear Information System (INIS)

    Wang, T.S.T.; Seldin, D.; Fawwaz, R.A.; Srivastava, S.; Olvwole, S.

    1989-01-01

    Recent advances in hybridoma technology have led to the development of monoclonal antibodies to a variety of antigens. The high degree of specificity of such reagents coupled with refinements in instrumentation and production of new radionuclides has rekindled interest in the application of radioimmunoscintigraphy in the diagnosis of various diseases. Although much of the work with monoclonal antibodies has been devoted to the diagnosis and treatment of tumors, increasing use is being made of these agents for the study of nontumor related disorders. This chapter focuses on the application of radioimmunoscintigraphy in the diagnosis of malignancies with a discussion on the other uses, notably those related to the vascular system

  6. Radiolabeling of anti-CD20 with Re-188 for treatment of Non-Hodgkin's lymphoma: radiochemical control

    International Nuclear Information System (INIS)

    Dias, C.R.; Osso Junior, J.A.

    2008-01-01

    Radioimmunotherapy (RIT) uses target-specific monoclonal antibodies or fragments labeled with a radioactive isotope to combine humoral and radiolytic functions and has the advantage of targeting not only the cell to which the antibody is bound but also the surrounding tumor cells and microenvironment. The most successful clinical studies of RIT in patients with Non-Hodgkin's Lymphoma (NHL) have targeted CD20+ Bcell tumors. Antibody therapy directed against the CD20 antigen on the surface of B-cells is considered one of the first successful target-specific therapies in oncology. The radionuclide rhenium-188 ( 188 Re) is currently produced from the father nuclide 188 W through a transportable generator system. Because of its easy availability and suitable nuclear properties (E βMAX = 2.1 MeV, t1/2 = 16.9 h, E γ = 155 keV), this radionuclide is considered an attractive candidate for application as therapeutic agent and could be conveniently utilized for imaging and dosimetric purposes. The objective of this work is the optimization of direct radiolabeling method of anti-CD20 with 188 Re using a liquid formulation. Anti-CD20 was reduced by incubation with 2-mercaptoethanol at room temperature. The number of resulting free sulphydryl groups was assayed with Ellman's reagent. Optimization of radiolabeling was achieved by varying parameters: antibody mass, reducing agent mass, tartrate mass, stability and reaction time, 188 Re volume and activity. Radiochemical purity of 188 Re-anti-CD20 was evaluated using instant thin layer chromatography-silica gel (ITLC-SG). Quality control methods for evaluation of radiochemical purity showed good labeling yield of the antibody but further studies will be carried out in order to improve the labeling yields and consequently the specific activity of the product. (author)

  7. 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

  8. Endobronchial administration of iodine-131 B72.3 monoclonal antibody in patients with lung cancer

    International Nuclear Information System (INIS)

    Del Vecchio, S.; Mansi, L.; Petrillo, A.; Camera, L.; Salvatore, M.; Sofia, M.; Marra, A.; Carratu, L.

    1991-01-01

    We tested the feasibility of endobronchial administration of radiolabelled monoclonal antibodies (MoAbs) and the biodistribution of the radiotracer. Ten patients with histological confirmed adenocarcinoma or squamous cell carcinoma were studied. Nine received 470 μCi (103 μg) of 131 I-B72.3, a monoclonal antibody reacting against TAG 72 antigen, while one patient received 502 μCi (291 μg) of 131 I-4C4, an indifferent antibody used for comparison in a negative control study. The radiolabelled antibody was administered through a flexible fiberoptic bronchoscope and placed on the tumour mass under visual monitoring. Scans with a large field-of-view gamma-camera showed retention of 131 I-B72.3 at the tumour site up to 6-9 days in six of eight patients. No other organs were visualized with the exception of faint activity in the gastrointestinal tract, bladder and thyroid. On the contrary, the indifferent antibody 131 I-4C4 was not retained at the tumour site 6 days after MoAbs administration, and more prominent activity was found in the gastrointestinal tract. In one patient the study was not technically adequate because of failure of the delivery system. The vascular compartment contained less than 3% of the administered dose. We conclude that endobronchial administration is a feasible technique and allows stable and specific targetting of bronchial tumours. Furthermore, the low activity found in the plasma and other organs suggests that this approach may be used to deliver therapeutic doses of MoAbs to lung cancers. (orig.)

  9. Use of an anti-platelet monoclonal antibody F (ab')2 fragment for imaging thrombus

    International Nuclear Information System (INIS)

    Loutfi, I.; Stuttle, A.W.J.; Peters, A.M.; George, P.; Lavender, J.P.; Lumley, P.

    1990-01-01

    Ten patients with suspected thrombus have been studied using 111 In-labelled F (ab')2 fragments of P256, a monoclonal antibody which recognizes an epitope on the platelet membrane glycoprotein IIb/IIIa complex. The F (ab')2 fragment was radiolabelled with 111 In via diethylenetri-aminepentamacetic acid to give a specific activity of up to 190 MBq (5mCi) mg - 1 without impairment of immunoreactivity. In vitro platelet aggregation studies showed that the F (ab')2 fragment caused less platelet aggregation than the whole antibody on a molar ratio and was without significant effect upon the sensitivity of platelets to a range of aggregating agents. Platalets were labelled in ten patients by intravenous injection of approximately 100 μg P256 F (ab')2. Of the ten patients studies, six showed localization of activity consistent with platelet accumulation. Localization was clearly seen when associated with thrombus of the lower limbs (three patients: deep vein thrombosis; one patient: aortofemoral graft), and was apparent although less marked in two other cases, one of aortic aneurysm and one of carotid stenosis. Use of radiolabelled P256 F (ab')2 offers a means of non-invasive detection of thrombus which, from in vitro studies, would appear to have less direct effect of platelet behaviour than the whole antibody. (author). 9 refs. 8 figs. 1 tab

  10. AL amyloid imaging and therapy with a monoclonal antibody to a cryptic epitope on amyloid fibrils.

    Directory of Open Access Journals (Sweden)

    Jonathan S Wall

    Full Text Available The monoclonal antibody 2A4 binds an epitope derived from a cleavage site of serum amyloid protein A (sAA containing a -Glu-Asp- amino acid pairing. In addition to its reactivity with sAA amyloid deposits, the antibody was also found to bind amyloid fibrils composed of immunoglobulin light chains. The antibody binds to synthetic fibrils and human light chain (AL amyloid extracts with high affinity even in the presence of soluble light chain proteins. Immunohistochemistry with biotinylated 2A4 demonstrated positive reaction with ALκ and ALλ human amyloid deposits in various organs. Surface plasmon resonance analyses using synthetic AL fibrils as a substrate revealed that 2A4 bound with a K(D of ∼10 nM. Binding was inhibited in the presence of the -Glu-Asp- containing immunogen peptide. Radiolabeled 2A4 specifically localized with human AL amyloid extracts implanted in mice (amyloidomas as evidenced by single photon emission (SPECT imaging. Furthermore, co-localization of the radiolabeled mAb with amyloid was shown in biodistribution and micro-autoradiography studies. Treatment with 2A4 expedited regression of ALκ amyloidomas in mice, likely mediated by the action of macrophages and neutrophils, relative to animals that received a control antibody. These data indicate that the 2A4 mAb might be of interest for potential imaging and immunotherapy in patients with AL amyloidosis.

  11. Kinetics of platelets in dogs with thrombocytopenia induced by antiglycoprotein IIb/IIIa receptor monoclonal antibody

    International Nuclear Information System (INIS)

    Hosono, Makoto; Sone, Naoaki; Endo, Keigo; Saga, Tsuneo; Kobayashi, Hisataka; Hosono, Masako N.; Sakahara, Harumi; Yasunaga, Kojiro; Konishi, Junji

    1995-01-01

    To experimentally assess the kinetics of platelets in thrombocytopenia, we constructed a canine model using 111 In-oxine labeled autologous platelets and an intact antiplatelet monoclonal antibody (MAb) NNKY2-11 (IgG2a). With the infusion of radiolabeled autologous platelets into dogs, the peripheral platelet count and blood radioactivity level were examined, and the radioactivity in the liver, spleen and heart was determined with scintigraphic analysis. Thereafter, i.v. injection of 100 μg/kg of NNKY2-11 had no effect on platelet counts or the biodistribution of radiolabeled platelets. However, 200 and 300 μg/kg of MAb reduced the platelets, and the radioactivity of the liver and spleen augmented clearly after injection of MAb. Platelet radioactivity in serum, which had decreased after MAb infusion, did not recover, even when peripheral platelet counts returned to the normal levels, indicating that these new platelets might be derived from the platelet-storage pool or new thrombocytogenesis. This model of antiplatelet MAb induced thrombocytopenia seems to be useful for analyzing the kinetics of platelets in thrombocytopenia

  12. Radioimmunodetection of human tumor xenografts by monoclonal antibody F(ab')/sub 2/ fragments

    Energy Technology Data Exchange (ETDEWEB)

    Herlyn, D.; Munz, D.L.; Herlyn, M.; Koprowski, H.; Powe, J.; Alavi, A.; Meinken, G.E.; Srivastava, S.C.

    1986-01-01

    Procedures are described for the radiolocalization of human tumors by murine monoclonal antibodies (MAb) in animal model systems. Visualization of tumor xenografts was clearer in nude mice compared to experimentally immunosuppressed mice due to the higher tumor viability. MAb localization in tumor tissue was greatly enhanced when F(ab')/sub 2/ fragments rather than intact antibody molecules were used. Although tumors could be visualized with /sup 131/I-, /sup 123/I-or /sup 111/In-labeled MAb fragments without background subtraction, tumor-to-background ratios of radioactivity were highest for /sup 131/I-labeled fragments. /sup 131/I-labeled F(ab')/sub 2/ fragments of eight MAb against human colorectal carcinoma, melanoma or lung carcinoma localized specifically only in those tumors that bound the MAb in vitro and not in unrelated tumors. Radiolabeled fragments of MAb with other specificities (anti-hepatitis virus MAb) did not localize in tumors. All MAb that inhibited tumor growth in nude mice effectively localized these tumors by ..gamma..-scintigraphy. Some MAb were effective in localizing tumors but ineffective in inhibiting their growth. The ability of the specific radiolabeled F(ab')/sub 2/ fragments to localize in tumor grafts correlated significantly with MAb binding affinity and density of antigenic sites on tumor cells together, but not with either in vitro binding parameter alone.

  13. Direct labelling of monoclonal antibodies with 99Tcm. Assessment of labelling, stability, immunoreactivity and biodistribution

    International Nuclear Information System (INIS)

    Janoki, G.A.

    1998-01-01

    Reduction of disulfide bonds to sulfhydryl groups for direct radiolabelling of monoclonal antibodies for immunoscintigraphic application continues to be of significant interest. Reducing agents that have been used are the following: stannous ion, 2-mercaptoethanol, dithiothreitol, dithioerythriol, and ascorbic acid. The radiolabelling of the reduced and purified antibody is performed via Sn 2+ reduction of pertechnetate in the presence of an excess of a low-affinity chelating ligand. In a recent work the 2-mercaptoethanol (2-ME) reduction based method was studied by using different analytical and biological techniques. Human IgG (Sandoglobulin), anti-CEA MoAb (ior-1), and anti-granulocyte MoAb (MAK 47), were reduced with 2-ME at two different molar ratios. To determine the amount of contaminating mercaptoethanol which may have survived the gel-filtration step 14 C-ME was used. The number of the free endogenous sulfhydryl groups generated by reduction was determined by Ellman's reagent; absorbance was measured at 412 nm. Within the quality assurance procedure of the 3 freeze dried kits the labelling efficiency, stability, pH, sterility, apyrogenicity, vial yield, syringe retention, filterable activity, free SH determination and animal distribution were studied again. After receiving permission from local ethics committee pilot human studies were initiated. Study protocols were also approved

  14. 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

  15. Effect of kinase inhibitors on the therapeutic properties of monoclonal antibodies.

    Science.gov (United States)

    Duong, Minh Ngoc; Matera, Eva-Laure; Mathé, Doriane; Evesque, Anne; Valsesia-Wittmann, Sandrine; Clémenceau, Béatrice; Dumontet, Charles

    2015-01-01

    Targeted therapies of malignancies currently consist of therapeutic monoclonal antibodies and small molecule kinase inhibitors. The combination of these novel agents raises the issue of potential antagonisms. We evaluated the potential effect of 4 kinase inhibitors, including the Bruton tyrosine kinase inhibitor ibrutinib, and 3 PI3K inhibitors idelalisib, NVP-BEZ235 and LY294002, on the effects of the 3 monoclonal antibodies, rituximab and obinutuzumab (directed against CD20) and trastuzumab (directed against HER2). We found that ibrutinib potently inhibits antibody-dependent cell-mediated cytotoxicity exerted by all antibodies, with a 50% inhibitory concentration of 0.2 microM for trastuzumab, 0.5 microM for rituximab and 2 microM for obinutuzumab, suggesting a lesser effect in combination with obinutuzumab than with rituximab. The 4 kinase inhibitors were found to inhibit phagocytosis by fresh human neutrophils, as well as antibody-dependent cellular phagocytosis induced by the 3 antibodies. Conversely co-administration of ibrutinib with rituximab, obinutuzumab or trastuzumab did not demonstrate any inhibitory effect of ibrutinib in vivo in murine xenograft models. In conclusion, some kinase inhibitors, in particular, ibrutinib, are likely to exert inhibitory effects on innate immune cells. However, these effects do not compromise the antitumor activity of monoclonal antibodies in vivo in the models that were evaluated.

  16. 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)

  17. Technetium-99m radiolabeling of a recombinant dermonecrotic protein (recLiD1) from the Loxosceles venom for biodistribution study

    International Nuclear Information System (INIS)

    Valadares, D.; Felicori, L.; Olortegui, C.C.; Simal, C.; Gouvea dos Santos, R.

    2007-01-01

    In the present study the recombinant form (recLiD1) of a dermonecrotic protein present in the Brazilian brown spider Loxosceles intermedia venom was labeled with technetium-99m using stannous chloride and sodium borohydride as reducing agents. 99mTc-recLiD 1 kept its biological activity evoking dermonecrotic activity in rabbits. In vivo biodistribution in mice with the radiolabeled recLiD 1 showed high kidney uptake followed by stomach and liver uptakes. Also, we can see that 20% of toxin remaining in the skin after 120 min and once absorbed, 99mTc-recLiD 1 is rapidly cleared from the blood with long-lasting. We also observed one displacement of 99mTc-recLiD 1 by one monoclonal antibody raised against L. intermedia venom that indicates specific interaction with kidney tissue. (author)

  18. Elevated Lipoprotein(A Impairs Platelet Radiolabeling Yield

    Directory of Open Access Journals (Sweden)

    Susanne Granegger

    2015-02-01

    Full Text Available Objectives: Platelet radiolabeling in clinical routine usually results in labeling efficiencies (LE above 80%. A variety of risk factors and clinical conditions are known to impair platelet labeling yield, among them elevated triglycerides and low-density lipoproteins. The potential influence of lipoprotein(a (Lp(a, an atherogenic lipoprotein particle containing a kringle subunit, which is widely found in the proteins of fibrinolysis pathway, has never been studied. Normal Lp(a levels range below 30 mg/ dl. The exact prevalence of elevated Lp(a is unknown, most likely ranging below 10%. Even more rare is an isolated elevation despite an otherwise normal lipoprotein profile. Methods: We examined the role of isolated elevated Lp(a (> 50 mg/dl, ranging up to 440 mg/dl compared to patients with normal lipid profile. Platelets were radiolabeled with in-111-oxine at 37 °C for 5 minutes using ISORBE-consensus methodology. Results: The findings indicate that already at levels below 100 mg/dl Lp(a decreases LE. LE assessment after cross-incubation of hyper-Lp(a platelets with normal Lp(a plasma and vice versa reveals that platelets rather than the plasmatic environment are responsible for the deterioration of labeling yield. This behavior already has been reported for elevated low-density lipoproteins. Apparently, the quantitative influence of LDL and Lp(a/mg is comparable. Plotting the sum of LDL and Lp(a versus LE reveals a clear significant negative correlation. Conclusion: As extremely elevated Lp(a, particularly above 150 mg/dl, may significantly impair labeling results. We therefore recommend to include extremely elevated Lp(a into the list of parameters, which should be known before performing radiolabeling of human platelets.

  19. Gene transfer strategies for improving radiolabeled peptide imaging and therapy

    International Nuclear Information System (INIS)

    Rogers, B.E.; Buchsbaum, D.J.; Zinn, K.R.

    2000-01-01

    Utilization of molecular biology techniques offers attractive options in nuclear medicine for improving cancer imaging and therapy with radiolabeled peptides. Two of these options include utilization of phage-panning to identify novel tumor specific peptides or single chain antibodies and gene transfer techniques to increase the antibodies and gene transfer techniques to increase the number of antigen/receptor sites expressed on malignant cells. The group has focused on the latter approach for improving radiolabeled peptide imaging and therapy. The most widely used gene transfer vectors in clinical gene therapy trials include retrovirus, cationic lipids and adenovirus. It has been utilized adenovirus vectors for gene transfer because of their ability to accomplish efficient in vivo gene transfer. Adenovirus vectors encoding the genes for a variety of antigens/receptors (carcinoembryonic antigen, gastrin-releasing peptide receptor, somatostatin receptor subtype 2 (SSTr2) have all shown that their expression is increased on cancer cells both in vitro and in vivo following adenovirus infection. Of particular interest has been the adenovirus encoding for SSTr2 (AdCMVSSTr2). Various radioisotopes have been attached to somatostatin analogues for imaging and therapy of SSTr2-positive tumors both clinically and in animal models. The use of these analogues in combination with AdCMVSSTr2 is a promising approach for improving the detection sensitivity and therapeutic efficacy of these radiolabeled peptides against solid tumors. In addition, it has been proposed the use of SSTr2 as a marker for imaging the expression of another cancer therapeutic transgene (e.g. cytosine deaminase, thymidine kinase) encoded within the same vector. This would allow for non-invasive monitoring of gene delivery to tumor sites

  20. A radiolabel release microassay for phagocytic killing of Candida albicans

    International Nuclear Information System (INIS)

    Bistoni, F.; Baccarini, M.; Blasi, E.; Marconi, P.; Puccetti, P.

    1982-01-01

    The chromium-51 release technique for quantifying intracellular killing of radiolabelled Candida albicans particles was exploited in a microassay in which murine and human phagocytes acted as effectors under peculiarly simple conditions. At appropriate effector: target ratios and with a 4 h incubation, up to 50% specific chromium release could be detected in the supernatant with no need for opsonization or lysis of phagocytes. This simple microassay permits easy-to-perform, simultaneous testing of a variety of different phagocytes even if only available in limited amounts, and provides an objective measurement of intracellular killing of Candida albicans. (Auth.)

  1. Radio-labelled quaternary compounds and their diagnostic use

    International Nuclear Information System (INIS)

    Woo, D.V.

    1984-01-01

    Radio-labelled compounds having a lipophilic cation, which are quaternary ammonium, phosphonium or arsonium halides, in which the halide is a chloride, bromide or iodide, and in which the four quaternary substituents are independently selected from Csub(1-3) alkyl, phenyl and benzyl, at least two substituents being phenyl or benzyl, and one phenyl or benzyl substituent carrying a ring-substituent selected from 123 I, 125 I, 131 I, 77 Br, 82 Br and 18 F. Such compounds can be administered by injection, and a radio-image of the myocardium obtained. (author)

  2. {sup 99m}Tc-rituximab radiolabelled by photo-activation: a new non-Hodgkin's lymphoma imaging agent

    Energy Technology Data Exchange (ETDEWEB)

    Gmeiner Stopar, T.; Fettich, J.; Hojker, S. [University Medical Centre Ljubljana, Department for Nuclear Medicine, Ljubljana (Slovenia); Mlinaric-Rascan, I. [University of Ljubljana, Faculty of Pharmacy, Ljubljana (Slovenia); Mather, S.J. [St Bartholomew' s Hospital, Cancer Research UK, Department Nuclear Medicine, London (United Kingdom)

    2006-01-01

    Rituximab was the first chimeric monoclonal antibody to be approved for treatment of indolent B-cell non-Hodgkin's lymphoma (NHL). It is directed against the CD20 antigen, which is expressed by 95% of B-cell NHLs. The aim of this study was to explore the possibility of radiolabelling rituximab with {sup 99m}Tc for use as an imaging agent in NHL for early detection, staging, remission assessment, monitoring for metastatic spread and tumour recurrence, and assessment of CD20 expression prior to (radio)immunotherapy. Rituximab was purified from Mabthera solution (Roche), photo-activated at 302 nm by UV irradiation and radiolabelled with {sup 99m}Tc. The effectiveness of the labelling method was evaluated by determination of the number of free thiol groups per photoreduced antibody, radiochemical purity and in vitro stability of {sup 99m}Tc-rituximab. On average, 4.4 free thiol groups per photoreduced antibody were determined. Radiolabelling yields greater than 95% were routinely observed after storage of the photo-activated antibody at -80 C for 195 days. The direct binding assay showed preserved ability of {sup 99m}Tc-rituximab to bind to CD20, with an average immunoreactive fraction of 93.3%. The internalisation rate was proven to be low, with only 5.3% of bound {sup 99m}Tc-rituximab being internalised over 4 h at 37 C. Our results demonstrate that {sup 99m}Tc-rituximab of high radiochemical purity and with preserved binding affinity for the antigen can be prepared by photoreduction and that the method shows good reproducibility. {sup 99m}Tc-rituximab will be further explored as an imaging agent applicable in NHL for the purposes mentioned above. (orig.)

  3. 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

  4. 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.

  5. 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

  6. Radiolabeled cypoxic cell sensitizers: tracer for assessment of ischemia

    International Nuclear Information System (INIS)

    Mathias, C.J.; Welch, M.J.; Kilbourn, M.R.; Jerabek, P.A.; Patrick, T.B.; Raichle, M.E.; Krohn, K.A.; Rasey, J.S.; Shaw, D.W.

    1987-01-01

    Hypoxic, non-functional, but viable, tissue may exist in heart and brain following an arterial occlusion. Identification of such tissue in vivo is crucial to the development of effective treatment strategies. It has been suggested that certain compounds capable of sensitizing hypoxic tumor cells to killing by x-rays (i.e., misonidazole) might serve as in vivo markers of hypoxic tissue in ischemic myocardium or brain if properly radiolabeled. To this end the authors have radiolabeled two fluorinated analogs of nitroimidazole based hypoxic cell sensitizers with the 110 minute half-lived positron-emitting fluorine-18. The ability of these tracers to quantitate the presence of hypoxic tissue has been studied in a gerbil stroke model. The in vivo uptake of one of these tracers [F-18]-fluoronormethyoxymisonidazole is dependent on the extent of tissue hypoxia, and thus, appears to have potential as a diagnostic indicator of non-functional but viable tissue when the tracer is used in conjunction with positron emission tomography. 80 references, 2 figures, 1 table

  7. Production of the radioactive antitumoral cisplatin

    International Nuclear Information System (INIS)

    Leal, Alexandre S.; Junior, Alvaro D. Carvalho; Abrantes, Fabiana M.; Menezes, Maria Angela de B.C.; Ferraz, Vany; Cruz, Tamara S.; Cardoso, Valbert N.; Oliveira, Monica C. de

    2006-01-01

    This work presents the preparation of radiolabelled cis-dichlorodiammineplatinum (II), CDDP*, sealed in a cadmium capsule. The irradiation of CDDP covered by cadmium, employing exposure times longer than 2 h, demonstrated good chemical purity and high specific activity. This finding allowed a better detection of in vivo CDDP* and suggests that it may be a good tool for studies of long-term biodistribution of pharmaceutical formulations containing this drug

  8. 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.

  9. 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

  10. Radiolabeling and Preclinical Evaluation of 131I-anti-CD20 for Non-Hodgkin's Lymphomas Therapy

    International Nuclear Information System (INIS)

    Kullaprawittaya, Usa; Khongpetch, Pranom; Ngamprayad, Tippanan; Nuanchuen, Suphatphong

    2007-08-01

    Full text: In this study, a monoclonal anti-CD20 was developed for radioimmunotherapy of non-Hodgkin's B-cell lymphoma by reacting anti-CD20 with iodine-131 using iodogen procedure. It was found that radiochemical yield was > 95 % independently of incubation time and the antibody could be conjugated with iodine-131 up to 10 mCi/mg. The radiolabeled antibody exhibited excellent retention of immunoreactivity with radio incorporations >95% for 6 hr at 4 o C. In vitro stability tests showed minimal loss of iodine-131 from the conjugate in the presence of cysteine and in human serum at 37 o C. Biodistribution study in normal ICR mice showed higher uptake by the liver, kidney and intestines but lower thyroid uptake compared to 131 I -MIBG. Biodistribution studies confirmed the in vitro stability of 131 I -anti-CD20. In particular, excellent in vivo retention of iodine-131 was demonstrated by lower thyroid accumulation over 48 hr. A favorable biological distribution of 131 I -anti-CD20 suggests this radiopharmaceutical may be effectively used in the therapy of non-Hodgkin's lymphoma

  11. Monoclonal Antibodies Against Fusicoccin with Binding Characteristics Similar to the Putative Fusicoccin Receptor of Higher Plants 1

    Science.gov (United States)

    Feyerabend, Martin; Weiler, Elmar W.

    1987-01-01

    Monoclonal antibodies were raised against fusicoccin. The toxin, linked to bovine serum albumin through its t-pentenyl moiety, served as immunogen. Hybridomas secreting anti-fusicoccin antibodies were screened by radioimmunoassay employing a novel radioactive derivative, [3H]-nor-fusicoccin-alcohol of high specific activity (1.5 × 1014Bq/mole). The two monoclonal antibodies reported here are of high apparent affinity for fusicoccin (0.71 × 10−9 molar and 1.85 × 10−9 molar). This is comparable to the apparent affinity of rabbit antiserum raised against the same type of conjugate (9.3 × 10−9 molar). A method for the single step purification of the monoclonal antibodies from ascites fluid is reported. A solid-phase immunoassay, using alkaline phosphatase as enzyme, exhibits a measuring range from 0.1 to 1.5 picomoles (about 70 picograms to 1 nanogram) of fusicoccin. The displacement of [3H]-nor-fusicoccin-alcohol from the antibodies by compounds structurally related to fusicoccin exhibits similar selectivity as a microsomal binding assay with the same tracer as radiolabeled probe. Images Fig. 2 PMID:16665786

  12. Quantitative autoradiographic mapping of focal herpes simplex virus encephalitis using a radiolabeled antiviral drug

    International Nuclear Information System (INIS)

    Price, R.

    1984-01-01

    A method of mapping herpes simplex viral infection comprising administering a radiolabeled antiviral active 5-substituted 1-(2'-deoxy-2'-substituted-D-arabinofuranosyl) pyrimidine nucleoside to the infected subject, and scanning the area in which the infection is to be mapped for the radiolabel

  13. A Single Domain–Based Anti-Her2 Antibody Has Potent Antitumor Activities

    Directory of Open Access Journals (Sweden)

    Xiaoqiong Wu

    2018-04-01

    Full Text Available Human epidermal growth factor receptor 2 (HER2 is overexpressed in approximately 20% to 30% of breast cancers and various other types of cancers, which plays a vital role in the cancer progression. Monoclonal antibodies targeting Her2 are now used in the clinic to treat Her2 overexpression cancer patients. However, relapse or resistance is frequent with the current therapies. To generate a new treatment avenue against Her2, we immunized and selected a specific anti-Her2 single domain antibody C3 for further studies. The C3-Fc antibody drove antibody-dependent cell-mediated cytotoxicity against Her2-positive tumor cells in vitro and resulted in potent antitumor growth in vivo. These data suggest that the C3-Fc antibody may provide an alternative avenue for Her2-positive cancer therapy.

  14. The Role of Anti-Drug Antibodies in the Pharmacokinetics, Disposition, Target Engagement, and Efficacy of a GITR Agonist Monoclonal Antibody in Mice.

    Science.gov (United States)

    Brunn, Nicholas D; Mauze, Smita; Gu, Danling; Wiswell, Derek; Ueda, Roanna; Hodges, Douglas; Beebe, Amy M; Zhang, Shuli; Escandón, Enrique

    2016-03-01

    Administration of biologics to enhance T-cell function is part of a rapidly growing field of cancer immunotherapy demonstrated by the unprecedented clinical success of several immunoregulatory receptor targeting antibodies. While these biologic agents confer significant anti-tumor activity through targeted immune response modulation, they can also elicit broad immune responses potentially including the production of anti-drug antibodies (ADAs). DTA-1, an agonist monoclonal antibody against GITR, is a highly effective anti-tumor treatment in preclinical models. We demonstrate that repeated dosing with murinized DTA-1 (mDTA-1) generates ADAs with corresponding reductions in drug exposure and engagement of GITR on circulating CD3(+) CD4(+) T cells, due to rapid hepatic drug uptake and catabolism. Mice implanted with tumors after induction of preexisting mDTA-1 ADA show no anti-tumor efficacy when given 3 mg/kg mDTA-1, an efficacious dose in naive mice. Nonetheless, increasing mDTA-1 treatment to 30 mg/kg in ADA-positive mice restores mDTA-1 exposure and GITR engagement on circulating CD3(+) CD4(+) T cells, thereby partially restoring anti-tumor efficacy. Formation of anti-mDTA-1 antibodies and changes in drug exposure and disposition does not occur in GITR(-/-) mice, consistent with a role for GITR agonism in humoral immunity. Finally, the administration of muDX400, a murinized monoclonal antibody against the checkpoint inhibitor PD-1, dosed alone or combined with mDTA-1 did not result in reduced muDX400 exposure, nor did it change the nature of the anti-mDTA-1 response. This indicates that anti-GITR immunogenicity may not necessarily impact the pharmacology of coadministered monoclonal antibodies, supporting combination immunomodulatory strategies. Copyright © 2016 by The American Society for Pharmacology and Experimental Therapeutics.

  15. Dual antibody therapy to harness the innate anti-tumor immune response to enhance antibody targeting of tumors.

    Science.gov (United States)

    Chester, Cariad; Marabelle, Aurelien; Houot, Roch; Kohrt, Holbrook E

    2015-04-01

    Cancer immunotherapy is a rapidly evolving field that offers a novel paradigm for cancer treatment: therapies focus on enhancing the immune system's innate and adaptive anti-tumor response. Early immunotherapeutics have achieved impressive clinical outcomes and monoclonal antibodies are now integral to therapeutic strategies in a variety of cancers. However, only recently have antibodies targeting innate immune cells entered clinical development. Innate immune effector cells play important roles in generating and maintaining antitumor immunity. Antibody-dependent cell-mediated cytotoxicity (ADCC) and antibody-dependent cellular phagocytosis (ADCP) are important innate immune mechanisms for tumor eradication. These cytolytic processes are initiated by the detection of a tumor-targeting antibody and can be augmented by activating co-stimulatory pathways or blocking inhibitory signals on innate immune cells. The combination of FDA-approved monoclonal antibodies with innate effector-targeting antibodies has demonstrated potent preclinical therapeutic synergy and early-phase combinatorial clinical trials are ongoing. Copyright © 2015 Elsevier Ltd. All rights reserved.

  16. Redox cycling of potential antitumor aziridinylquinones

    NARCIS (Netherlands)

    Lusthof, Klaas J.; de Mol, Nicolaas J.; Richter, Wilma; Janssen, Lambert H.M.; Butler, John; Hoey, Brigid M.; Verboom, Willem; Reinhoudt, David

    1992-01-01

    The formation of reactive oxygen intermediates (ROI) during redox cycling of newly synthetized potential antitumor 2,5-bis (1-aziridinyl)-1,4-benzoquinone (BABQ) derivatives has been studied by assaying the production of ROI (superoxide, hydroxyl radical, and hydrogen peroxide) by xanthine oxidase

  17. Hypoxia-targeting antitumor prodrugs and photosensitizers

    International Nuclear Information System (INIS)

    Zhang Zhouen; Nishimoto, S.I.

    2006-01-01

    Tumor hypoxia has been identified as a key subject for tumor therapy, since hypoxic tumor cells show resistance to treatment of tumor tissues by radiotherapy, chemotherapy and phototherapy. For improvement of tumor radiotherapy, we have proposed a series of radiation-activated prodrugs that could selectively release antitumor agent 5-fluorouracil or 5-fluorodeoxyuridine under hypoxic conditions. Recently, we attempted to develop two families of novel hypoxia-targeting antitumor agents, considering that tumor-hypoxic environment is favorable to biological and photochemical reductions. The first family of prodrugs was derived from camptothecin as a potent topoisomerase I inhibitor and several bioreductive motifs. These prodrugs could be activated by NADPH-cytochrome P450 reductase or DT-diaphorase to release free camptothecin, and thereby showed hypoxia-selective cytotoxictiy towards tumor cells. These prodrugs were also applicable to the real-time monitoring of activation and antitumor effect by fluorometry. Furthermore, the camptothecin-bioreductive motif conjugates was confirmed to show an oxygen-independent DAN photocleaving activity, which could overcome a drawback of back electron transfer occurring in the photosensitized one-electron oxidation of DNA. Thus, these camptothecin derivatives could be useful to both chemotherapy and phototherapy for hypoxic tumor cells. The second family of prodrugs harnessed UV light for cancer therapy, incorporating the antitumor agent 5-fluorourcil and the photolabile 2-nitrobenzyl chromophores. The attachment of a tumor-homing cyclic peptide CNGRC was also employed to construct the prototype of tumor-targeting photoactiaved antitumor prodrug. These novel prodrugs released high yield of 5-fluorourcil upon UV irradiation at λ ex =365 nm, while being quite stable in the dark. The photoactivation mechanism was also clarified by means of nanosecond laser flash photolysis. (authors)

  18. Immunoscintigraphy and radioimmunotherapy in Cuba: experiences with labeled monoclonal antibodies for cancer diagnosis and treatment (1993-2013).

    Science.gov (United States)

    Peña, Yamilé; Perera, Alejandro; Batista, Juan F

    2014-01-01

    tumor response in a substantial percentage of patients. CONCLUSIONS Cuba has experience with production and radiolabeling of monoclonal antibodies, which facilitates use of these agents. Studies in Cuba conducted by the Clinical Research Center over the past 20 years have yielded satisfactory results. Evidence obtained suggests promising potential of monoclonal antibodies and nuclear medicine, with immunoscintigraphy and radioimmunotherapy techniques providing alternatives for cancer diagnosis and treatment in Cuba.

  19. Quantitation of passive cutaneous anaphylaxis (PCA) by using radiolabelled antigen

    International Nuclear Information System (INIS)

    Ring, J.; Seifert, J.; Brendel, W.

    1978-01-01

    The major problem of detecting reaginic antibody by passive cutaneous anaphylaxis (PCA) is the quantitation of the dye reaction. Radiolabelled antigen was used in an attempt to quantitate the PCA reaction (Radio-PCA). Antisera containing reaginic antibody against human serum albumin (HSA) were produced in rabbits. These antisera were injected into normal rabbit skin in different dilutions. Twentyfour hours later HSA was injected intravenously either with Evans Blue or as 125-I-HSA. Radioactivity found in antibody-containing skin was significantly higher than in control specimens containing saline or normal rabbit serum, as low as antiserum dilutions of 1:1,000. Compared with Evans Blue technique Radio-PCA was able to distinguish quantitatively between different antiserum dilutions at a higher level of statistical significance. (author)

  20. Radiolabeling of liposomes and polymeric micelles with PET-isotopes

    DEFF Research Database (Denmark)

    Jensen, Andreas Tue Ingemann

    as a revolution in modern therapeutics, especially in chemotherapy. A major reason is the ability of nanoparticles to accumulate in tumor tissue. Liposomes are the classic nanoparticle, consisting of a lipid membrane with an aqueous core. Polymeric micelles are made from amphiphilic detergent‐like copolymers......This thesis is divided into three separate chapters that can be read independently. Chapter 1 is a general introduction, touching upon liposomes and polymeric micelles and radiolabeling with 18F and 64Cu. Chapter 2 and 3 address two separate research projects, each described below. A complete......‐life only allowing up to 8 hours scans. 18F must be covalently attached to components of the liposome. By binding to a lipid, it can be stably lodged in the membrane. A glycerolipid and a cholesteryl ether were synthesized with free primary alcohols and a series of their sulphonates (Ms, Ts, Tf) were...

  1. Development of Novel Radio-labeled Materials using Research Reactor

    International Nuclear Information System (INIS)

    Choi, Sun Ju; Hong, Y. D.; Choi, K. H.

    2010-04-01

    In this project, we aim to develop the novel radiomaterials using reactor-produced radioisotope for the targeted therapy of cancer. At initial stage, we have examined the effect of beta particle-emission radionuclides on the proliferation of various types of tumor cells and found that beta particle emission radionuclides significantly inhibited the proliferation of tumor cells. We have synthesized new bifunctional chelating agents (BFCAs) for bio-conjugation with bio-active molecules, such as peptide and antibody, and radioabeling with radionuclide. For targeted radiotherapy, we have prepared target materials and radiolabeled with various radionuclides using BFCAs and obtained candidate materials for the treatment of melanoma. We have next treated melanoma-induced animals with candidate radiopharmaceuticals. The tumor growth was significantly reduced by treatment with candidates, and survival rate of the animals was prolonged, suggesting that candidate radiopharmaceuticals are promising agents for the treatment of melanoma

  2. Aspects of monitoring and quality assurance for radiolabeled antibodies

    International Nuclear Information System (INIS)

    Barber, D.E.

    1992-06-01

    This report provides an informational resource and guide for the US Nuclear Regulatory Commission (NRC) and NRC licensees who produce or use radiolabeled antibodies (RABs). Components of quality assurance programs related to the production and use of RABs are reviewed and evaluated, and recommendations are made on dosage calibrations, exposure control, monitoring, and personnel requirements. Special emphasis is placed on dose calibrators because these instruments are used extensively to measure the dosage of radiopharmaceuticals to be administered to patients. The difficulties of using dose calibrators to quantify dosages of beta- and alpha-emitters are discussed. The advantages and disadvantages of using other instruments are examined, and recommendations are made on the types of instruments to be used for different applications. 46 refs., 8 tabs

  3. Therapy with radiolabelled somatostatin analogs in neuroendocrine tumors

    International Nuclear Information System (INIS)

    Kunikowska, J.; Krolicki, L.

    2007-01-01

    In the 80's the discovery of somatostatin receptors expression on NET cells enabled the application of somatostatin analogues in diagnosis and therapy. Initially, 'cold' somatostatin analogs were used for therapeutical purpose, with overall good clinical response, but with minimal anti-proliferation effect. Furthermore, radiolabelled receptor-binding peptides have been shown to be an important class of radiopharmaceuticals for tumor diagnosis and therapy with minimal side-effects. Specific binding between receptor on tumor cell and peptide with beta emitting radionuclide act not only on tumor related symptoms but also on tumor cell via radiotoxic effect of beta radiation. Discoveries of next receptor combinations, allow the work over synthesis and applications of next receptors' analogs both in diagnosis and in therapy. Due to complex characteristics of NET's, the use therapeutic 'cocktail' containing the variety analogs may be of great importance. (author)

  4. Utilisation of radiolabeled antibiotic for the diagnosis of infectious foci

    International Nuclear Information System (INIS)

    Khammassi, Sabrine; Gharbi, Sabrine

    2009-01-01

    Nuclear imaging is a non-invasive exploration technique, used for rapid diagnostic of infectious disease .Thus, for osteoarticular infection scintigraphic techniques were proposed to ameliorate the diagnostic sensibility and the use of radiolabeled antibiotics as imaging agents of infectious loci become more and more recognized. In this work, a new sulfanil amid derivative, the N sulfanilamide-ferrocene-carboxamide was chemically synthesized then labeled with technetium-99m, with a radiochemical yield, 87 pour cent. In in-vitro studies were done with E.coli. first , the up-take of labeled molecule was estimated as 40 pour cent. Then, the bacteriostatic al effect of the molecule was de terminated by considering the Optical Density at 600 nm. The obtained results, encourage us to do more, with biodistribution on normal and infected mice; with Staphylococcus aureus. Then to carry out scintigraphic imaging with gamma camera to check out the potentiality of the molecule as an infectious imaging agent. (Author)

  5. Optimized procedures for manganese-52: Production, separation and radiolabeling

    DEFF Research Database (Denmark)

    Fonslet, Jesper; Tietze, Sabrina; Jensen, Andreas Tue Ingemann

    2017-01-01

    ±0.4×105. An additional AG 1-X8 column was used to remove copper, iron, cobalt and zinc impurities from the prepared 52Mn in 8M HCl. The macrocyclic chelator DOTA was rapidly radiolabeled with 52Mn in aq. ammonium acetate (pH 7.5R.T.) with a radiochemical yield >99% within 1min and was stable for >2 days in bovine serum......Pressed chromium-powder cyclotron targets were irradiated with 16MeV protons, producing 52Mn with average yields of 6.2±0.8MBq/µAh. Separation by solid-phase anion exchange from ethanol-HCl mixtures recovered 94.3±1.7% of 52Mn and reduced the chromium content by a factor of 2.2...

  6. Tissue distribution of radiolabeled phosphatidylserine-containing liposome in mice

    Energy Technology Data Exchange (ETDEWEB)

    Borborema, Samanta E.T.; Nascimento, Nanci do [Instituto de Pesquisas Energeticas e Nucleares (IPEN/CNEN-SP), Sao Paulo, SP (Brazil). Centro de Biotecnologia], e-mail: samanta@usp.br, e-mail: nnascime@ipen.br; Andrade Junior, Heitor F. de [Instituto de Medicina Tropical de Sao Paulo (IMTSP), Sao Paulo, SP (Brazil)], e-mail: hfandrad@usp.br; Osso Junior, Joao A. [Instituto de Pesquisas Energeticas e Nucleares (IPEN/CNEN-SP), Sao Paulo, SP (Brazil). Centro de Radiofarmacia], e-mail: jaosso@ipen.br

    2009-07-01

    Liposomes are used as drug delivery systems to modify pharmacokinetic of drugs and also to improve their action in target cells. Liposomes containing phosphatidylserine are efficiently eliminated from the blood by cells of the mononuclear phagocytic system (MPS), predominantly Kupffer cells in the liver. In this way, this is a valuable approach to treat infectious diseases involving MPS, especially leishmaniasis. Leishmaniasis is a severe parasitic disease, caused by intramacrophage protozoa Leishmania sp., and is fatal if left untreated. Leishmania resides mainly in the liver and the spleen. Antileishmanial agents containing-liposomes showed more effective therapies with reduction of toxicity and adverse side effects. The purpose of this study was to investigate the tissue distribution of radioactive meglumine antimoniate encapsulated in phosphatidylserine-containing liposome. Meglumine antimoniate was neutron irradiated inside the IEA-R1 nuclear reactor to produce antimony radiotracers, {sup 122}Sb and {sup 124}Sb, and encapsulated in liposome. Healthy mice received a single intraperitoneal dose of the radiolabeled drug. Analysis of the mean radioactive tissue concentration-time data curves showed that liver and spleen had the highest levels of radioactivity. In addition these levels of drug remained for more than 48 hours. The dominant route of elimination was via biliary excretion with slow rate. Small fraction of the drug was found in the kidneys with very fast elimination. In conclusion, the phosphatidylserine-containing liposome showed to be a very useful tool to target antileishmanial agents to MPS and to sustain the drug levels for longer times. Besides, radiolabeled liposome is the easiest approach to perform biodistribution evaluation. (author)

  7. Tissue distribution of radiolabeled phosphatidylserine-containing liposome in mice

    International Nuclear Information System (INIS)

    Borborema, Samanta E.T.; Nascimento, Nanci do; Osso Junior, Joao A.

    2009-01-01

    Liposomes are used as drug delivery systems to modify pharmacokinetic of drugs and also to improve their action in target cells. Liposomes containing phosphatidylserine are efficiently eliminated from the blood by cells of the mononuclear phagocytic system (MPS), predominantly Kupffer cells in the liver. In this way, this is a valuable approach to treat infectious diseases involving MPS, especially leishmaniasis. Leishmaniasis is a severe parasitic disease, caused by intramacrophage protozoa Leishmania sp., and is fatal if left untreated. Leishmania resides mainly in the liver and the spleen. Antileishmanial agents containing-liposomes showed more effective therapies with reduction of toxicity and adverse side effects. The purpose of this study was to investigate the tissue distribution of radioactive meglumine antimoniate encapsulated in phosphatidylserine-containing liposome. Meglumine antimoniate was neutron irradiated inside the IEA-R1 nuclear reactor to produce antimony radiotracers, 122 Sb and 124 Sb, and encapsulated in liposome. Healthy mice received a single intraperitoneal dose of the radiolabeled drug. Analysis of the mean radioactive tissue concentration-time data curves showed that liver and spleen had the highest levels of radioactivity. In addition these levels of drug remained for more than 48 hours. The dominant route of elimination was via biliary excretion with slow rate. Small fraction of the drug was found in the kidneys with very fast elimination. In conclusion, the phosphatidylserine-containing liposome showed to be a very useful tool to target antileishmanial agents to MPS and to sustain the drug levels for longer times. Besides, radiolabeled liposome is the easiest approach to perform biodistribution evaluation. (author)

  8. Compartmental modeling approach to the radiation dosimetry of radiolabeled antibody

    International Nuclear Information System (INIS)

    Zanzonico, P.B.; Bigler, R.E.; Primus, F.J.; Alger, E.; DeJager, R.; Stowe, S.; Ford, E.; Brennan, K.; Goldenberg, D.M.

    1986-01-01

    Essential for the calculation of absorbed doses from systemically administered radiolabled antibody is the determination of the total number of nuclear transformations in specified source regions. Compartmental analysis (using biodistribution data augmented with a priori physiological information), unlike simply integrating empirical time-activity curves, may enable one to calculate the cumulated activity in unsampled as well as sampled source regions. These may include microscopic source regions (e.g. the intracellular space, cell surface, and extracellular space) important for microdosimetry calculations. Of particular importance is the interaction between the anti-tumor antibody and the tumor antigen. 30 references, 9 figures, 2 tables

  9. Golimumab and certolizumab: The two new anti-tumor necrosis factor kids on the block

    Directory of Open Access Journals (Sweden)

    Mittal Mohit

    2010-01-01

    Full Text Available Anti-tumor necrosis factor (anti-TNF agents have revolutionized treatment of psoriasis and many other inflammatory diseases of autoimmune origin. They have considerable advantages over the existing immunomodulators. Anti-TNF agents are designed to target a very specific component of the immune-mediated inflammatory cascades. Thus, they have lower risks of systemic side-effects. In a brief period of 10 years, a growing number of biological therapies are entering the clinical arena while many more biologicals remain on the horizon. With time, the long-term side-effects and efficacies of these individual agents will become clearer and help to determine which ones are the most suitable for long-term care. Golimumab (a human monoclonal anti-TNF-α antibody and Certolizumab (a PEGylated Fab fragment of humanized monoclonal TNF-α antibody are the two latest additions to the anti-TNF regimen. Here, we are providing a brief description about these two drugs and their uses.

  10. 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.

  11. Preparation and radiolabeling of human serum albumin (HSA)-coated magnetite nanoparticles for magnetically targeted therapy

    International Nuclear Information System (INIS)

    Zhang Chunfu; Cao Jinquan; Yin Duanzhi; Wang Yongxian; Feng Yanlin; Tan Jiajue

    2004-01-01

    In this paper, we describe the preparation of human serum albumin-coated magnetic particles of about 200 nm in diameter with narrow size distribution radiolabeled with 188 Re for the purpose of magnetically targeted therapy. The optimum radiolabeling conditions are: SnCl 2 ·2H 2 O 8 mg/ml, citric acid 20 mg/ml, vitamin C 8 mg/ml, labeling volume 500 μl and a reaction time of 3 h. The stability of the radiolabeled particles is suitable for in vivo study

  12. Preparation and radiolabeling of human serum albumin (HSA)-coated magnetite nanoparticles for magnetically targeted therapy

    Energy Technology Data Exchange (ETDEWEB)

    Zhang Chunfu E-mail: zchunfu@yahoo.com.cn; Cao Jinquan; Yin Duanzhi; Wang Yongxian; Feng Yanlin; Tan Jiajue

    2004-12-01

    In this paper, we describe the preparation of human serum albumin-coated magnetic particles of about 200 nm in diameter with narrow size distribution radiolabeled with {sup 188}Re for the purpose of magnetically targeted therapy. The optimum radiolabeling conditions are: SnCl{sub 2}{center_dot}2H{sub 2}O 8 mg/ml, citric acid 20 mg/ml, vitamin C 8 mg/ml, labeling volume 500 {mu}l and a reaction time of 3 h. The stability of the radiolabeled particles is suitable for in vivo study.

  13. Development of monoclonal-antibody-based products for medical research and diagnostic imaging. Technical report, 28 January 1987-31 December 1988 (Final)

    International Nuclear Information System (INIS)

    Rhodes, B.A.; Pant, K.D.; Chauhan, N.; Buckelew, J.; Budd, P.

    1989-04-01

    Two major areas of application of monoclonal antibodies were examined: the development of products to support the 'Antibody Delivery System', a parent-specific and variable antibody formula drug system for use in imaging and treatment of cancer, and the development of an antibody-based radiopharmaceutical for imaging occult abscesses and other conditions involving high concentrations of white blood cells. In development of the Antibody Delivery System components, methods for characterization and purification of monoclonal antibodies were developed and validated; a dot immunoassay test, under the name RhoDot (TM) Immunoassay, was developed for matching antibodies to putative tumor specimen: a radioimmunoassay, under the name PhoChek (TM) Quality Control Test Kit for Radiolabeled Antibodies, was developed and commercialized for measuring the immunoreactive fraction of radiolabeled antibodies specific to colorecal cancer; and a patient-specific quality control test was developed. In development of the antibody-based radiopharmaceutical for imaging occult abscesses, a candidate antibody was identified and produced under U.S. Food and Drug Administration standards preparatory to human clinical trials

  14. Evaluation of tetrazolium-based semiautomatic colorimetric assay for measurement of human antitumor cytotoxicity

    International Nuclear Information System (INIS)

    Heo, D.S.; Park, J.G.; Hata, K.; Day, R.; Herberman, R.B.; Whiteside, T.L.

    1990-01-01

    A 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide (MTT)-based colorimetric assay was developed and compared with 51Cr release from different adherent tumor cell targets (human squamous cell carcinoma lines of the head and neck established in our laboratory, melanoma, and colorectal carcinoma) using 5-7-day human lymphokine-activated killer cells and monocyte-depleted peripheral blood lymphocytes as effectors. With adherent tumor cell targets, MTT colorimetry was more sensitive than the 51Cr release assay in measuring the antitumor activity of effectors: median, 4385 (range, 988-8144) versus median, 1061 (range, 582-7294) lytic units (the number of effector cells required to lyse 20% of 5 x 10(3) targets)/10(7) effectors (P less than 0.01). Background effects (without effector cells) were comparable in 4-h assays (9% versus 10%) between MTT colorimetry and 51Cr release. In 24-h assays, MTT colorimetry showed higher antitumor activity (70-100% versus 40-60% lysis at 1:1 effector:target cell ratio) but lower background effects (6% versus 38%) than 51Cr release assay. Thus, MTT colorimetry was more sensitive, did not use radiolabeled targets, required fewer effector cells, and was easier, less expensive, and better adaptable to serial monitoring of effector cell function in cancer patients. This colorimetric assay is especially well suited to adherent tumor cell targets. The use of adherent tumor cell monolayers, as opposed to trypsinized single cell suspensions, provides an opportunity to measure interactions of effector cells with enzymatically unaltered solid tumor targets. Because of the greater sensitivity of the colorimetric assay, the transformation of MTT data into lytic units, as commonly used for 51Cr release assays, required an adjustment to avoid the extrapolation based on the exponential fit equation

  15. Antitumor and immunomodulatory activity of Inonotus obliquus

    Directory of Open Access Journals (Sweden)

    Staniszewska Justyna

    2017-06-01

    Full Text Available The article presents the antitumor and immunomodulatory activity of compounds and extracts from Inonotus obliquus. Polysaccharides isolated from sclerotium have a direct antitumor effect due to protein synthesis inhibition in tumor cells. Polysaccharides derived from the mycelium function by activating the immune system. Due to the limited toxicity of these substances, both extracts as well as isolated and purified chemicals may be a good alternative to current chemotherapy and play a role in cancer prevention. In vitro experiments have shown the inhibition of inflammation with the influence of action of I. obliquus extracts; however, in vivo experiments on animals implanted with tumor cells of different types have shown the activation of the host immune system. This led to decrease in tumor mass and prolonged survival. The immunomodulatory mechanism of action is complex and it seems that stimulation of macrophages and induction of apoptosis in cancer cells is of great importance.

  16. Antitumor Activities of Kushen: Literature Review

    Directory of Open Access Journals (Sweden)

    Mingyu Sun

    2012-01-01

    Full Text Available To discover and develop novel natural compounds with therapeutic selectivity or that can preferentially kill cancer cells without significant toxicity to normal cells is an important area in cancer chemotherapy. Kushen, the dried roots of Sophora flavescens Aiton, has a long history of use in traditional Chinese medicine to treat inflammatory diseases and cancer. Kushen alkaloids (KS-As and kushen flavonoids (KS-Fs are well-characterized components in kushen. KS-As containing oxymatrine, matrine, and total alkaloids have been developed in China as anticancer drugs. More potent antitumor activities were identified in KS-Fs than in KS-As in vitro and in vivo. KS-Fs may be developed as novel antitumor agents.

  17. Positron tomographic imaging of tumors using monoclonal antibodies. Final progress report, April 15, 1989--October 31, 1995

    International Nuclear Information System (INIS)

    Zalutsky, M.R.

    1997-02-01

    The overall objective of this research is to develop methods for utilizing positron emission tomography (PET) to increase the clinical potential of radiolabeled monoclonal antibodies (MAbs). Enhancement of MAb tumor localization by hyperthermia also was proposed. Studies were to have been performed with both 18 F and 124 I; however, the lack of its availability (until quite recently) prevented experiments with 124 I. Instead, two additional lines of inquiry were initiated in which they utilized aspects of the radiofluorination chemistries originally developed for MAbs for labeling chemotactic peptides and meta-iodobenzylguanidine (MIBG) analogues with 18 F. This final report summarizes the original specific aims and the main research accomplishments in studies of mouse, dog and human models

  18. Positron tomographic imaging of tumors using monoclonal antibodies. Final progress report, April 15, 1989--October 31, 1995

    Energy Technology Data Exchange (ETDEWEB)

    Zalutsky, M.R.

    1997-02-01

    The overall objective of this research is to develop methods for utilizing positron emission tomography (PET) to increase the clinical potential of radiolabeled monoclonal antibodies (MAbs). Enhancement of MAb tumor localization by hyperthermia also was proposed. Studies were to have been performed with both {sup 18}F and {sup 124}I; however, the lack of its availability (until quite recently) prevented experiments with {sup 124}I. Instead, two additional lines of inquiry were initiated in which they utilized aspects of the radiofluorination chemistries originally developed for MAbs for labeling chemotactic peptides and meta-iodobenzylguanidine (MIBG) analogues with {sup 18}F. This final report summarizes the original specific aims and the main research accomplishments in studies of mouse, dog and human models.

  19. Impact of antitumor therapy on nutrition

    International Nuclear Information System (INIS)

    Kokal, W.A.

    1985-01-01

    The treatment of the cancer patient by surgery, chemotherapy or radiation therapy can impose significant nutritional disabilities on the host. The nutritional disabilities seen in the tumor-bearing host from antitumor therapy are produced by factors which either limit oral intake or cause malabsorption of nutrients. The host malnutrition caused as a consequence of surgery, chemotherapy or radiation therapy assumes even more importance when one realizes that many cancer patients are already debilitated from their disease

  20. Systematic screening of bryophytes for antitumor agents

    OpenAIRE

    Spjut, Richard W.; Kingston, David G. I.; Cassady, John M.

    1992-01-01

    References are made to cytotoxic and/or antitumor compounds that have been isolated - ansamitocin P-3 from Claopodium crispifolium (Hook.) Ren. & Card. and Anomodon attenuatus Hueb., or an associated actinomycete, and ohioensins and pallidisetums from Polytrichum spp. Several hundred collections, which have been obtained from temperate regions of North America during 1990 and 1991, are currently being screened in new bioassays; active sesquiterpene lactones have been recently isolated from sp...

  1. Antitumor Immunity Is Controlled by Tetraspanin Proteins

    Directory of Open Access Journals (Sweden)

    Fleur Schaper

    2018-05-01

    Full Text Available Antitumor immunity is shaped by the different types of immune cells that are present in the tumor microenvironment (TME. In particular, environmental signals (for instance, soluble factors or cell–cell contact transmitted through the plasma membrane determine whether immune cells are activated or inhibited. Tetraspanin proteins are emerging as central building blocks of the plasma membrane by their capacity to cluster immune receptors, enzymes, and signaling molecules into the tetraspanin web. Whereas some tetraspanins (CD81, CD151, CD9 are widely and broadly expressed, others (CD53, CD37, Tssc6 have an expression pattern restricted to hematopoietic cells. Studies using genetic mouse models have identified important immunological functions of these tetraspanins on different leukocyte subsets, and as such, may be involved in the immune response against tumors. While multiple studies have been performed with regards to deciphering the function of tetraspanins on cancer cells, the effect of tetraspanins on immune cells in the antitumor response remains understudied. In this review, we will focus on tetraspanins expressed by immune cells and discuss their potential role in antitumor immunity. New insights in tetraspanin function in the TME and possible prognostic and therapeutic roles of tetraspanins will be discussed.

  2. Radiolabelled peptides and nanoparticles for specific molecular targeting in oncology

    International Nuclear Information System (INIS)

    Helbok, A.

    2011-01-01

    The aim of this thesis is the development of radiolabelled peptides and nanoparticles (NP) for specific molecular targeting in oncology. Three different types of NP were investigated in this study: lipid - based NP (liposomes and micelles), human serum albumin - based NP (albumin NP) and protamine - oligonucleotide - based NP (proticles). In a first step, radiolabelling protocols were set up for the different NP - formulations. The variety of radioisotopes used, covers the whole spectrum of applications in nuclear medicine: SPECT (111In, 99mTc), (2) PET (68Ga) and therapeutic applications (177Lu, 90Y) opening a manifold administration potential for these NP aiming towards multiple targeting and hybrid imaging strategies (combined SPECT / PET and MRI). Radiolabelling quality was analyzed by instant thin layer chromatography (ITLC). High radiochemical yields (RCY >90 %) and high specific activity (SA) were achieved. NP - formulations were derivatized with the chelating agent Diethylenetriaminepentaacetic acid (DTPA) allowing complexation of trivalent radiometals, and potentially nonradioactive metals, such as Gd3+, for MRI imaging leading to the development of multifunctionalized NP for a unified labelling approach. Furthermore, NP were derivatized with the pharmacokinetic modifier polyethylene glycol (PEG) to maintain NP with long circulating ability. Stability assessments included incubation in different media (serum, 4 mM DTPA - solution and PBS pH 7.4, at 37 o C for a period of 24 h). For the in vivo biodistribution of the NP, static and / or dynamic SPECT / PET imaging studies were performed at different time points with Lewis rats and correlated to results from quantification of tissue - uptake. Results indicate differences in stability and general pharmacokinetic behaviour depended on the NP - formulation. However, a positive influence expressed in a prolonged retention time in circulation was investigated for all different NP - formulations due to PEG

  3. 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.

  4. Radiolabeling and biodistribution of 62Cu-dithiocarbamate

    International Nuclear Information System (INIS)

    Matsumoto, Kazuya; Fujibayashi, Yasuhisa; Yokoyama, Akira; Konishi, Junji.

    1990-01-01

    The newly developed 62 Zn/ 62 Cu generator system has made available the production of the short-lived 62 Cu (T 1/2 = 9.8 min) positron radionuclide, eluted as 62 Cu-glycine. In the search for 62 Cu labeled radiopharmaceuticals for positron CT (PET) brain diagnostic studies, two ligands N,N-diethyl- and N,N-dimethyl-dithiocarbamic acid (DDC and DmDC) were selected, based on their Cu chelating abilities and the neutral lipophilic character of their copper chelates. In the present work, an in vitro study with non-radioactive Cu-glycine showed that both ligands easily formed the stable, neutral Cu-DDC and Cu-DmDC chelates (1:2 metal-ligand complexes) based on the ligand exchange reaction. Then the 62 Zn/ 62 Cu generator eluate, the 62 Cu-glycine was used for the radiolabeling of DDC and DmDC. The following HPLC analysis revealed that the ligand exchange reaction proceeded rapidly; the radiochemical purities of 62 Cu-DDC and 62 Cu-DmDC were extremely high (non-detectable 62 Cu-glycine) and both chelates were more lipophilic than 62 Cu-glycine. The mouse biodistribution of both radiolabeled compounds, 62 Cu-DDC and 62 Cu-DmDC indicated a brain accumlation of 2.8 and 5.3 times higher than 62 Cu-glycine, 15 min post injection, respectively. The brain accumulation observed with both 62 Cu-DDC and 62 Cu-DmDC might be due to their stable, neutral and lipophilic character; the latter enhanced by the presence of the methylated side chains. The gathered results indicated the applicability of dithiocarbamic acid derivatives in the production of new 62 Cu-labeled compounds using the 62 Zn/ 62 Cu generator system based on the ligand exchange reaction with 62 Cu-glycine eluate. Further studies with Cu-dithiocarbamic acid derivatives for development of new generator-produced 62 Cu positron radiopharmaceuticals can be recalled. (author)

  5. Regional and systemic distribution of anti-tumor x anti-CD3 heteroaggregate antibodies and cultured human peripheral blood lymphocytes in a human colon cancer xenograft

    International Nuclear Information System (INIS)

    Nelson, H.; Ramsey, P.S.; Kerr, L.A.; McKean, D.J.; Donohue, J.H.

    1990-01-01

    Anti-tumor antibody (317G5) covalently coupled to an anti-CD3 antibody (OKT3) produces a heteroaggregate (HA) antibody that can target PBL to lyse tumor cells expressing the appropriate tumor Ag. The i.v. and i.p. distribution of radiolabeled HA antibody 317G5 x OKT3 and of radiolabeled cultured human PBL were studied in athymic nude mice bearing solid intraperitoneal tumor established from the human colon tumor line, LS174T. Mice were injected with 125I-labeled HA antibody, 125I-labeled anti-tumor mAb, or 111In-labeled PBL, and at designated timepoints tissues were harvested and measured for radioactivity. 125I-317G5 x OKT3 localized specifically to tumor sites. Tumor radioactivity levels (percent injected dose/gram) were lower with 125I-317G5 x OKT3 HA antibody than with 125I-317G5 anti-tumor mAb, but were similar to levels reported for other anti-tumor mAb. The major difference in radioactivity levels observed between i.v. and i.p. administration of 125I-317G5 x OKT3 was an increase in hepatic radioactivity after i.v. HA antibody administration. HA antibodies produced from F(ab')2 fragments, which exhibit decreased m. w. and decreased Fc receptor-mediated binding, demonstrated improved tumor:tissue ratios as compared to intact antibody HA. 125I-317G5 F(ab')2 x OKT3 F(ab')2 antibody levels were equivalent to intact HA antibody levels in tumor, but were lower than intact HA antibody levels in the blood, bowel, and liver. Tumor:bowel ratios (20:1 at 48 h) were highest when 317G5 F(ab')2 x OKT3 F(ab')2 was injected i.p. Autoradiography confirmed that anti-tumor x anti-CD3 HA antibodies localized specifically to intraperitoneal tumor; that i.p. administered HA antibodies penetrated tumor directly; and that i.v. administered HA antibodies distributed along tumor vasculature

  6. 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

  7. 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.

  8. 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...

  9. 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

  10. 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.

  11. Radioimmunoimaging of experimental thrombi in dogs using technetium-99m-labeled monoclonal antibody fragments reactive with human platelets

    International Nuclear Information System (INIS)

    Som, P.; Oster, Z.H.; Zamora, P.O.; Yamamoto, K.; Sacker, D.F.; Brill, A.B.; Newell, K.D.; Rhodes, B.A.

    1986-01-01

    Monoclonal antibody 50H.19, which reacts with human platelets, was converted to fragments, pretinned, and made into kits for subsequent radiolabeling with /sup 99m/Tc. The antibody, which cross-reacts with dog platelets, was used to evaluate in vitro binding to blood clots and in vivo in experimental thrombi in dogs. After radiolabeling, 97.4 +/- 6.4% of the /sup 99m/Tc was antibody-associated. The preparations retained immunoreactivity, as determined by: binding studies using whole blood and determining the ratio of cell-to-plasma radioactivity (ratios of 57.6-61.2) and binding of the antibody to clots (clot/serum ratios were 57.2-74.6%). Approximately 50% of the radioactivity was cleared from the blood in 3-6 min and 18-24% was excreted in urine within 3 hr. Experimental thrombi in dogs could be visualized consistently within 2-3 hr postinjection in peripheral veins and arteries, pulmonary arteries, and the right ventricle. In addition, damage to blood vessel intima without visible thrombi could also be detected. This method has the following advantages: short and simple pre-imaging preparation, and rapid visualization of thrombi with no need for blood-pool subtraction or delayed imaging

  12. Evaluation of radiolabeled ruthenium compounds as tumor-localizing agents

    International Nuclear Information System (INIS)

    Srivastava, S.C.; Richards, P.; Meinken, G.E.; Som, P.; Atkins, H.L.; Larson, S.M.; Grunbaum, Z.; Rasey, J.S.; Clarke, M.H.; Dowling, M.

    1979-01-01

    This work introduces a new class of radiopharmaceuticals based on ruthenium-97. The excellent physical properties of Ru-97, the high chemical reactivity of Ru, the potential antitumor activity of several Ru coordination compounds, and BLIP production of Ru-97, provide a unique combination for the application of this isotope in nuclear oncology. A systematic study was undertaken on the synthesis, characterization, and evaluation of a number of ruthenium-labeled compounds. In a variety of animal tumor models, several compounds show considerable promise as tumor-localizing agents when compared to gallium-67 citrate. The compounds studied (with Ru in different oxidation states) include ionic Ru, a number of hydrophilic and lipophilic chelates, and various ammine derivatives

  13. An Efficient and Straightforward Method for Radiolabeling of Nanoparticles with {sup 64}Cu via Click Chemistry

    Energy Technology Data Exchange (ETDEWEB)

    Lee, Dong-Eun [Advanced Radiation Technology Institute, Korea Atomic Energy Research Institute, Jeongeup 580-185 (Korea, Republic of); Kim, Kwangmeyung [Center for Theragnosis, Biomedical Research Institute, Korea Institute of Science and Technology (KIST), Seoul 136-791 (Korea, Republic of); Park, Sang Hyun [Advanced Radiation Technology Institute, Korea Atomic Energy Research Institute, Jeongeup 580-185 (Korea, Republic of); Department of Radiobiotechnology and Applied Radioisotope Science, Korea University of Science and Technology, Deajeon 305-350 (Korea, Republic of)

    2015-07-01

    Recently, nanoparticles have received a great deal of interest in diagnosis and therapy applications. Since nanoparticles possess intrinsic features that are often required for a drug delivery system and diagnosis, they have potential to be used as platforms for integrating imaging and therapeutic functions, simultaneously. Intrinsic issues that are associated with theranostic nanoparticles, particularly in cancer treatment, include an efficient and straightforward radiolabeling method for understanding the in vivo biodistribution of nanoparticles to reach the tumor region, and monitoring therapeutic responses. Herein, we investigated a facile and highly efficient strategy to prepare radiolabeled nanoparticles with {sup 64}Cu via a strain-promoted azide, i.e., an alkyne cycloaddition strategy, which is often referred to as click chemistry. First, the azide (N3) group, which allows for the preparation of radiolabeled nanoparticles by copper-free click chemistry, was incorporated into glycol chitosan nanoparticles (CNPs). Second, the strained cyclooctyne derivative, dibenzyl cyclooctyne (DBCO) conjugated with a 1,4,7,10-tetraazacyclododecane- 1,4,7,10-tetraacetic acid (DOTA) chelator, was synthesized for preparing the pre-radiolabeled alkyne complex with {sup 64}Cu radionuclide. Following incubation with the {sup 64}Cu-radiolabeled DBCO complex (DBCO-PEG4-Lys-DOTA-{sup 64}Cu with high specific activity, 18.5 GBq/μ mol), the azide-functionalized CNPs were radiolabeled successfully with {sup 64}Cu, with a high radiolabeling efficiency and a high radiolabeling yield (>98%). Importantly, the radiolabeling of CNPs by copper-free click chemistry was accomplished within 30 min, with great efficiency in aqueous conditions. After {sup 64}Cu-CNPs were intravenously administered to tumor-bearing mice, the real time, in vivo biodistribution and tumor-targeting ability of {sup 64}Cu-CNPs were quantitatively evaluated by micro-PET images of tumor-bearing mice. These results

  14. New surface radiolabeling schemes of super paramagnetic iron oxide nanoparticles (SPIONs) for biodistribution studies†

    Science.gov (United States)

    Nallathamby, Prakash D.; Mortensen, Ninell P.; Palko, Heather A.; Malfatti, Mike; Smith, Catherine; Sonnett, James; Doktycz, Mitchel J.; Gu, Baohua; Roeder, Ryan K.; Wang, Wei; Retterer, Scott T.

    2016-01-01

    Nanomaterial based drug delivery systems allow for the independent tuning of the surface chemical and physical properties that affect their biodistribution in vivo and the therapeutic payloads that they are intended to deliver. Additionally, the added therapeutic and diagnostic value of their inherent material properties often provides extra functionality. Iron based nanomaterials with their magnetic properties and easily tailorable surface chemistry are of particular interest as model systems. In this study the core radius of the iron oxide nanoparticles (NPs) was 14.08 ± 3.92 nm while the hydrodynamic radius of the NPs, as determined by Dynamic Light Scattering (DLS), was between 90–110 nm. In this study, different approaches were explored to create radiolabeled NPs that are stable in solution. The NPs were functionalized with polycarboxylate or polyamine surface functional groups. Polycarboxylate functionalized NPs had a zeta potential of –35 mV and polyamine functionalized NPs had a zeta potential of +40 mV. The polycarboxylate functionalized NPs were chosen for in vivo biodistribution studies and hence were radiolabeled with 14C, with a final activity of 0.097 nCi mg–1 of NPs. In chronic studies, the biodistribution profile is tracked using low-level radiolabeled proxies of the nanoparticles of interest. Conventionally, these radiolabeled proxies are chemically similar but not chemically identical to the non-radiolabeled NPs of interest. This study is novel as different approaches were explored to create radiolabeled NPs that are stable, possess a hydrodynamic radius of <100 nm and most importantly they exhibit an identical surface chemical functionality as their non-radiolabeled counterparts. Identical chemical functionality of the radiolabeled probes to the non-radiolabeled probes was an important consideration to generate statistically similar biodistribution data sets using multiple imaging and detection techniques. The radiolabeling approach

  15. New surface radiolabeling schemes of super paramagnetic iron oxide nanoparticles (SPIONs) for biodistribution studies.

    Science.gov (United States)

    Nallathamby, Prakash D; Mortensen, Ninell P; Palko, Heather A; Malfatti, Mike; Smith, Catherine; Sonnett, James; Doktycz, Mitchel J; Gu, Baohua; Roeder, Ryan K; Wang, Wei; Retterer, Scott T

    2015-04-21

    Nanomaterial based drug delivery systems allow for the independent tuning of the surface chemical and physical properties that affect their biodistribution in vivo and the therapeutic payloads that they are intended to deliver. Additionally, the added therapeutic and diagnostic value of their inherent material properties often provides extra functionality. Iron based nanomaterials with their magnetic properties and easily tailorable surface chemistry are of particular interest as model systems. In this study the core radius of the iron oxide nanoparticles (NPs) was 14.08 ± 3.92 nm while the hydrodynamic radius of the NPs, as determined by Dynamic Light Scattering (DLS), was between 90-110 nm. In this study, different approaches were explored to create radiolabeled NPs that are stable in solution. The NPs were functionalized with polycarboxylate or polyamine surface functional groups. Polycarboxylate functionalized NPs had a zeta potential of -35 mV and polyamine functionalized NPs had a zeta potential of +40 mV. The polycarboxylate functionalized NPs were chosen for in vivo biodistribution studies and hence were radiolabeled with (14)C, with a final activity of 0.097 nCi mg(-1) of NPs. In chronic studies, the biodistribution profile is tracked using low level radiolabeled proxies of the nanoparticles of interest. Conventionally, these radiolabeled proxies are chemically similar but not chemically identical to the non-radiolabeled NPs of interest. This study is novel as different approaches were explored to create radiolabeled NPs that are stable, possess a hydrodynamic radius of <100 nm and most importantly they exhibit an identical surface chemical functionality as their non-radiolabeled counterparts. Identical chemical functionality of the radiolabeled probes to the non-radiolabeled probes was an important consideration to generate statistically similar biodistribution data sets using multiple imaging and detection techniques. The radiolabeling approach

  16. Intratumoral IL-12 and TNF-alpha-loaded microspheres lead to regression of breast cancer and systemic antitumor immunity.

    Science.gov (United States)

    Sabel, Michael S; Skitzki, Joseph; Stoolman, Lloyd; Egilmez, Nejat K; Mathiowitz, Edith; Bailey, Nicola; Chang, Wen-Jian; Chang, Alfred E

    2004-02-01

    Local, sustained delivery of cytokines at a tumor can enhance induction of antitumor immunity and may be a feasible neoadjuvant immunotherapy for breast cancer. We evaluated the ability of intratumoral poly-lactic-acid-encapsulated microspheres (PLAM) containing interleukin 12 (IL-12), tumor necrosis factor alpha (TNF-alpha), and granulocyte-macrophage colony stimulating factor (GM-CSF) in a murine model of breast cancer to generate a specific antitumor response. BALB/c mice with established MT-901 tumors underwent resection or treatment with a single intratumoral injection of PLAM containing IL-12, TNF-alpha, or GM-CSF, alone or in combination. Two weeks later, lymph nodes and spleens were harvested, activated with anti-CD3 monoclonal antibodies (mAb) and rhIL-2, and assessed for antitumor reactivity by an interferon gamma (IFNgamma) release assay. Tumor-infiltrating lymphocyte (TIL) analysis was performed on days 2 and 5 after treatment by mechanically processing the tumors to create a single cell suspension, followed by three-color fluorescence-activated cell sorter (FACS) analysis. Intratumoral injection of cytokine-loaded PLAM significantly suppressed tumor growth, with the combination of IL-12 and TNF-alpha leading to increased infiltration by polymorphonuclear cells and CD8+ T-cells in comparison with controls. The induction of tumor-specific reactive T-cells in the nodes and spleens, as measured by IFN-gamma production, was highest with IL-12 and TNF-alpha. This treatment resulted in resistance to tumor rechallenge. A single intratumoral injection of IL-12 and TNF-alpha-loaded PLAM into a breast tumor leads to infiltration by polymorphonuclear cells and CD8+ T-cells with subsequent tumor regression. In addition, this local therapy induces specific antitumor T-cells in the lymph nodes and spleens, resulting in memory immune response.

  17. Microassay for measurement of binding of radiolabelled ligands to cell surface molecules

    International Nuclear Information System (INIS)

    Woof, J.M.; Burton, D.R.

    1988-01-01

    An improved technique for measuring the binding of radiolabelled ligands to cell surface molecules has been developed by modification of a procedure using centrifugation through a water-immiscible oil to separate free and cell-bound ligand. It maximises the percentage of ligand bound since cell-bound and free ligand can be separated easily and reproducibly even when very small reaction volumes are used. This permits low levels of ligand radiolabelling and relatively low numbers of cells to be used

  18. A radiolabeled antiglobulin test for crossmatching platelet transfusions

    International Nuclear Information System (INIS)

    Kickler, T.S.; Braine, H.G.; Ness, P.M.; Koester, A.; Bias, W.

    1983-01-01

    Despite the use of HLA-matched platelets for alloimmunized recipients, transfusion failures occur. In order to reduce these failures, researchers investigated the use of a radiolabeled antiglobulin technique for platelet crossmatching. The principle of the test is that of an indirect Coombs test using 125 I labeled goat anti-human IgG. Incompatibility is determined by calculating a radioactivity antiglobulin test (RAGT) index. Using this technique, researchers performed 89 crossmatches on 19 leukemic or aplastic patients who were refractory to random donor platelets and receiving varying degrees of HLA-matched platelets. Effectiveness of the transfusion was assessed from the posttransfusion corrected platelet count increment (CCI) determined at 1 and 20 hr. When the RAGT index was 1.9 or less, the mean CCI at 1 lhr was 17,570 +/- 7003/cu mm, n . 55. When the RAGT index was 2.0 or greater, the mean CCI was 4237 +/- 4100/cu mm, n . 34. At 20 hr when the RAGT index was 1.9 or less, the mean CCI was 8722 +/- 3143/cu mm, n . 33, and when the index was 2.0 or greater, the mean CCI was 571 +/- 1286/cu mm, n . 23. Using this technique, one false negative resulted. Nine positive crossmatches with good increments at 1 hr were found; at 20 hr, however, the survival of these units was zero. These data suggest that this method is a useful adjunct in the selection of platelets in the refractory patient

  19. Radiolabeling of liposomes and polymeric micelles with PET-isotopes

    Energy Technology Data Exchange (ETDEWEB)

    Ingemann Jensen, A.T.

    2013-06-01

    This thesis is divided into three separate chapters that can be read independently. Chapter 1 is a general introduction, touching upon liposomes and polymeric micelles and radiolabeling with 18F and 64Cu. Chapter 2 and 3 address two separate research projects, each described below. A complete reference list is compiled in the end, immediately after the three chapters. This is followed by the supplementary information, divided into appropriate sections. Finally, the two first-authored manuscripts are attached as appendices. Chapter 1. The field of nanoparticulate drug delivery has been hailed as a revolution in modern therapeutics, especially in chemotherapy. A major reason is the ability of nanoparticles to accumulate in tumor tissue. Liposomes are the classic nanoparticle, consisting of a lipid membrane with an aqueous core. Polymeric micelles are made from amphiphilic detergent-like copolymers, that self-assemble in water. Therapy with nanoparticles is hampered by often poor tumor accumulation, combined with massive uptake by macrophages in the liver and spleen. For this reason, visualizing nanoparticle pharmacokinetics in-vivo is a valuable tool in the on-going research. Such visualization can be done by labeling with radio isotopes. Isotopes that emit positrons (PET-isotopes) can be detected by PET (positron emission tomography) technology, an accurate technique that has gained popularity in recent years. PET-isotopes of interest include 18F and 64Cu. In addition to being a research tool, radiolabeled nanoparticles hold promise as a radiopharmaceutical in themselves, as a means of imaging tumor tissue, aiding in diagnosis and surgery. Chapter 2. A method for labeling liposomes with 18F (97% positron decay, T = 110 min) was investigated. 18F is widely available, but is hampered by a short half-life only allowing up to 8 hours scans. 18F must be covalently attached to components of the liposome. By binding to a lipid, it can be stably lodged in the membrane. A

  20. Diagnostic and therapeutic perspectives in nuclear medicine: radiolabelled biomolecules

    International Nuclear Information System (INIS)

    Ferro F, G.; Murphy, C.A. de; Pedraza L, M.; Melendez A, L.

    2003-01-01

    From their beginning, the radiopharmaceuticals chemistry has gone to the study of the molecular chemistry. The radiopharmaceuticals are only in their capacity to detect such specific biochemical places as the receivers and the enzymes. With the recent obtaining of the complete structural sequence of the genome, it doesn't fit doubt of the importance that they have acquired the molecular images for the study from the genetic information to the alterations phenotypic in the chemistry of the human body. So, the future of the diagnostic and therapeutic nuclear medicine, practically is based in the study of protein fragments, peptide structures and chains of DNA radiolabelled for the study of the metabolism In vivo. These investigations represent a substantial change in those paradigms of the pharmaceutical development, when using the own organic capacities as source of medications, instead of considering to the organism like a simple assay tube where molecules act, like they are most of the traditional medications. The investigation of new techniques to design complex stable of Tc-99m, Re-188, Lu-177, Y-90 and Dy-166/Ho-l66 with biomolecules that don't alter the specificity and in general the molecular properties of the same ones. it is a topic of world interest in the environment of the radiopharmaceutical chemistry. In this work some achievements and perspectives are presented on those main diagnostic and therapeutic radiopharmaceuticals of third generation. (Author)

  1. Radiolabeling of liposomes and polymeric micelles with PET-isotopes

    International Nuclear Information System (INIS)

    Ingemann Jensen, A.T.

    2013-01-01

    This thesis is divided into three separate chapters that can be read independently. Chapter 1 is a general introduction, touching upon liposomes and polymeric micelles and radiolabeling with 18F and 64Cu. Chapter 2 and 3 address two separate research projects, each described below. A complete reference list is compiled in the end, immediately after the three chapters. This is followed by the supplementary information, divided into appropriate sections. Finally, the two first-authored manuscripts are attached as appendices. Chapter 1. The field of nanoparticulate drug delivery has been hailed as a revolution in modern therapeutics, especially in chemotherapy. A major reason is the ability of nanoparticles to accumulate in tumor tissue. Liposomes are the classic nanoparticle, consisting of a lipid membrane with an aqueous core. Polymeric micelles are made from amphiphilic detergent-like copolymers, that self-assemble in water. Therapy with nanoparticles is hampered by often poor tumor accumulation, combined with massive uptake by macrophages in the liver and spleen. For this reason, visualizing nanoparticle pharmacokinetics in-vivo is a valuable tool in the on-going research. Such visualization can be done by labeling with radio isotopes. Isotopes that emit positrons (PET-isotopes) can be detected by PET (positron emission tomography) technology, an accurate technique that has gained popularity in recent years. PET-isotopes of interest include 18F and 64Cu. In addition to being a research tool, radiolabeled nanoparticles hold promise as a radiopharmaceutical in themselves, as a means of imaging tumor tissue, aiding in diagnosis and surgery. Chapter 2. A method for labeling liposomes with 18F (97% positron decay, T = 110 min) was investigated. 18F is widely available, but is hampered by a short half-life only allowing up to 8 hours scans. 18F must be covalently attached to components of the liposome. By binding to a lipid, it can be stably lodged in the membrane. A

  2. Osteomyelitis diagnosis by {sup 99m}Tc radiolabeled aptamers

    Energy Technology Data Exchange (ETDEWEB)

    Santos, S.R.; Ferreira, I.M.; Andrade, A.S.R., E-mail: sararoberta7@hotmail.com, E-mail: imendesf@yahoo.com.br, E-mail: antero@cdtn.br [Centro de Desenvolvimento da Tecnologia Nuclear (CDTN/CNEN-MG), Belo Horizonte, MG (Brazil); Barros, A.L.B.; Cardoso, V.N.; Diniz, O.F., E-mail: brancodebarros@yahoo.com.br, E-mail: valbertcardoso@yahoo.com.br, E-mail: simoneodilia@yahoo.com.br [Universidade Federal de Minas Gerais (UFMG), Belo Horizonte, MG (Brazil). Faculdade de Farmacia. Departamento de Analises Clinicas e Toxicologicas

    2015-07-01

    Osteomyelitis, which is characterized by progressive inflammatory destruction and new opposition of bone, is still a difficult infection to treat. The clinical diagnosis in late stages is achieved easily, but an early diagnosis is more challenging. Staphylococcus aureus is a common agent found in osteomyelitis and bone prostheses infection. Diagnosis by scintigraphy has advantages because it is a non-invasive procedure and is able to perform an early diagnosis even before anatomic changes. Thus, nuclear medicine could contribute to an accurate diagnosis since specific radiopharmaceuticals were developed. In this study, aptamers selected to Staphylococcus aureus were labeled with {sup 99m}Tc and used for bacteria identification in an osteomyelitis experimental model. The aptamers selected to S. aureus were directly labelled with {sup 99m}Tc and were evaluated by biodistribution studies. Wistar rats with intraosseous infection in the right paw were used. A random aptamer labelled with {sup 99m}Tc was as control. Six animals were used in each group. The aptamers labeled with {sup 99m}Tc were able to identify the infection foci caused by S. aureus displaying a target/non-target ratio of 2,23 ± 0,20, after 3 h. The control group presented a target/non-target ratio 1,08 ± 0.23. The results indicated that the radiolabeled aptamers were able to identify specifically the infection foci and they should be further explored for infection diagnosis by scintigraphy. (author)

  3. Radiolabeled bivalent haptens for tumor immunodetection and radioimmunotherapy

    Energy Technology Data Exchange (ETDEWEB)

    Gruaz-Guyon, A.; Janevik-Ivanovska, E.; Raguin, O. [Hopital Saint-Antoine, Faculte' de Medecine, Paris (France); De Labriolle-Vaylet, C. [Hopital Saint-Antoine, Faculte' de Medecine, Paris (France); Hopital Saint-Antoine, Service de Medecine Nucleaire, Paris (France); Barbet, J. [Universite' de la Mediterranee, Faculte' de Medecine, Marseille (France)

    2001-06-01

    The pre targeting technique referred to as the Affinity Enhancement System (AES) uses bispecific antibodies and radiolabeled bivalent haptens that bind cooperatively to target cells in vivo. Experimental and clinical data demonstrate that DTPA bivalent haptens can deliver large radiation doses to tumor cells with high tumor to normal tissue contrast ratios and long activity residence time in tumors. Preliminary clinical results of radioimmunotherapy of medullary thyroid carcinomas and lung cancers look promising. Very encouraging results in biodistribution and radioimmunotherapy experiments in animals have been obtained with new haptens bearing two histamine-hemisuccinate suitable for {sup 131}I, {sup 99m}Tc and {sup 188}Re labeling. Targeting isotopes to double antigen positive tumor cells provides a binding enhancement that increases specificity for tumor cells as compared to single antigen targeting on normal cells. This approach may be beneficial for targeting isotopes to B type acute lymphoblastic leukemia and Burkitt lymphoma, as well as others tumors co-expressing two markers of low specificity, and might increase tumor irradiation with minimal irradiation of normal cells.

  4. Radiolabeled bivalent haptens for tumor immunodetection and radioimmunotherapy

    International Nuclear Information System (INIS)

    Gruaz-Guyon, A.; Janevik-Ivanovska, E.; Raguin, O.; De Labriolle-Vaylet, C.; Barbet, J.

    2001-01-01

    The pre targeting technique referred to as the Affinity Enhancement System (AES) uses bispecific antibodies and radiolabeled bivalent haptens that bind cooperatively to target cells in vivo. Experimental and clinical data demonstrate that DTPA bivalent haptens can deliver large radiation doses to tumor cells with high tumor to normal tissue contrast ratios and long activity residence time in tumors. Preliminary clinical results of radioimmunotherapy of medullary thyroid carcinomas and lung cancers look promising. Very encouraging results in biodistribution and radioimmunotherapy experiments in animals have been obtained with new haptens bearing two histamine-hemisuccinate suitable for 131 I, 99m Tc and 188 Re labeling. Targeting isotopes to double antigen positive tumor cells provides a binding enhancement that increases specificity for tumor cells as compared to single antigen targeting on normal cells. This approach may be beneficial for targeting isotopes to B type acute lymphoblastic leukemia and Burkitt lymphoma, as well as others tumors co-expressing two markers of low specificity, and might increase tumor irradiation with minimal irradiation of normal cells

  5. Radiolabeled Cetuximab Conjugates for EGFR Targeted Cancer Diagnostics and Therapy

    Directory of Open Access Journals (Sweden)

    Wiebke Sihver

    2014-03-01

    Full Text Available The epidermal growth factor receptor (EGFR has evolved over years into a main molecular target for the treatment of different cancer entities. In this regard, the anti-EGFR antibody cetuximab has been approved alone or in combination with: (a chemotherapy for treatment of colorectal and head and neck squamous cell carcinoma and (b with external radiotherapy for treatment of head and neck squamous cell carcinoma. The conjugation of radionuclides to cetuximab in combination with the specific targeting properties of this antibody might increase its therapeutic efficiency. This review article gives an overview of the preclinical studies that have been performed with radiolabeled cetuximab for imaging and/or treatment of different tumor models. A particularly promising approach seems to be the treatment with therapeutic radionuclide-labeled cetuximab in combination with external radiotherapy. Present data support an important impact of the tumor micromilieu on treatment response that needs to be further validated in patients. Another important challenge is the reduction of nonspecific uptake of the radioactive substance in metabolic organs like liver and radiosensitive organs like bone marrow and kidneys. Overall, the integration of diagnosis, treatment and monitoring as a theranostic approach appears to be a promising strategy for improvement of individualized cancer treatment.

  6. Radiolabeling oligo nuclieotide with 90Y and its radiolysis

    International Nuclear Information System (INIS)

    Liu Changbin; Tian Jiahe; Zhang Jinming; Yin Dayi; Guo Zhe

    2005-01-01

    Objective: To evaluate labeling Morpholinos (MORF), a DNA analogue, with 90 Y using p-isothiocyanatobenzyl-1,4,7,10-tetraazacyclododecane-1,4,7,10-tetraacetic acid (DOTA) as chelater and assess its stability and hybridization in vitro. Methods: A 25 mer MORF with a primary amine on the 3' equivalent end attached via a 10 member linker was conjugated with an isothiocyanate backbone derivative of DOTA. The conjugated product was labeled in various buffers over a different range of concentrations (0.5-2 mol/L) and pH(3-8.5). The labeled MORF was investigated for stability and hybridization in vitro. Results: By size exclusion high performance liquid chromatogram (HPLC) and instant thin layer chromatography (ITLC) analysis, the DOTA conjugated MORF was successfully radiolabeled, the labeling efficiency was (50 ± 12)%, the specific radioactivity was 5.05 x 10 6 MBq/mmol, radiochemistry purity >95%. The labeled MORF showed one sharp peak by HPLC that shifted completely to earlier retention times following addition of a polymer conjugated with the complementary MORF. In saline at room temperature and in serum at 37 degree C, the radioactivity profile of 90 Y showed a pronounced lower molecular weight peak which did not shifted and was shown due to 90 Y-DOTA resulting from radiolysis. Conclusion: MORF can be successfully labeled with 90 Y via DOTA as chelater, but care it must be taken to avoid the effect of radiolysis. (authors)

  7. 99mTc-tetrapeptides: radiolabelling and biodistribution in rats

    International Nuclear Information System (INIS)

    Laznickova, A.; Laznicek, M.; Trejtnar, F.; Mather, S.J.

    1998-01-01

    Preparation of 99m Tc-labelled tetrapeptides, namely acetyl-Gly-Gly-Cys-Gly (I), acetyl-Ser-Ser-Cys-Gly (II) and acetyl-Gly-Gly-Cys-Lys (III), analysis of their radiochemical purity and biodistribution were investigated in rats. The aim was to determine the relationship between structure and biological behaviour of 99m Tc-labelled peptides which are formed by amino-acid sequences capable of chelating technetium useful as universal chelators in ''hybrid'' peptides composed of receptor-specific part and the part chelating technetium. For labelling with 99m Tc, a conventional transchelation from 99m Tc-gluconate was used and radiolabelled peptides were purified by filtration on Whatman microfilters 12 kD. Radiochemical purity was higher than 98%. Biodistribution studies in rats showed that all agents are rapidly cleared from the body mostly via urine, but some part of administered radioactivity also in the faces was found. The later route of elimination way increased in the order III 99m Tc-MAG3. The results obtained will assist with design of optimal biocompatible tetrapeptides as chelators for formation of hybrid receptor-specific peptides. (author)

  8. Uptake of radiolabeled leukocytes in prosthetic graft infection

    International Nuclear Information System (INIS)

    Serota, A.I.; Williams, R.A.; Rose, J.G.; Wilson, S.E.

    1981-01-01

    The utility of radionuclide labeled leukocytes in the demonstration of infection within vascular prostheses was examined. The infrarenal aorta was replaced with a 3 cm Dacron graft in 12 dogs. On the third postoperative day, six of the animals received an intravenous injection of 10(8) Staphylococcus aureus. Labeled leukocyte scans were performed at postoperative days one and three, and then weekly for 8 weeks with indium-111 and technetium-99 labeled autologous leukocytes. When scans showed focal uptake of isotope in the area of prosthetic material, the grafts were aseptically excised and cultured on mannitol-salt agar. Both control and infected animals had retroperitoneal isotope activity in the immediate postoperative period that disappeared by the end of the first week. By the eighth postoperative week, all of the animals that received the bacteremic challenge had both radionuclide concentration in the region of the vascular prosthesis and S. aureus cultured subsequently from the perigraft tissues. None of the control animals had either radionuclide or bacteriologic evidence of infection at the eighth postoperative week. The radiolabeled leukocyte scan is a highly sensitive and specific technique, clinically applicable for the diagnosis of vascular prosthetic infections

  9. Synthesis and applications of radiolabelled drugs in pharmaceutical development

    International Nuclear Information System (INIS)

    Landvatter, S.W.; Heys, J.R.; Garner, K.T.; Mack, J.F.; Senderoff, S.G.; Shu, A.Y.; Villani, A.J.; Saunders, D.

    1994-01-01

    Radiolabelled drugs play a vital role in the development of new pharmaceuticals including application in drug discovery, pre-clinical development and clinical development. The synthesis of these pharmaceuticals in tritium or carbon-14 labelled form poses many challenges for the synthetic organic chemist. The actual choice of synthetic route must take into account the small scale, limited choice and high cost of labelled precursors, and the positioning of the label into a metabolically stable position. There are, however, a number of synthetic strategies available for overcoming these constraints. Although in some C-14 syntheses the requisite labelled raw material can be purchased and the existing synthesis adapted for labelling, frequently the synthetic challenge is the synthesis of a structurally simple, yet commercially unavailable, labelled precursor (e.g., γ-butyrolactone-[2- 14 C], cyclohexanone-[ 3 H], CuCN-[ 14 C], 2-furancarboxaldehyde-[ 14 C]). Another useful strategy in C-14 synthesis is the conversion of an advanced intermediate, or perhaps the unlabelled product itself, into a precursor which can then be reconverted into the labelled version of the intermediate. Occasionally, a new total synthesis must be developed. In addition to these strategies, tritium labelling can uniquely take advantage of exchange labelling techniques, synthesis and reduction of unsaturated precursors, or tritium-halogen replacement reactions. Examples of these strategies and use of the labelled products are discussed

  10. Osteomyelitis diagnosis by 99mTc radiolabeled aptamers

    International Nuclear Information System (INIS)

    Santos, S.R.; Ferreira, I.M.; Andrade, A.S.R.; Barros, A.L.B.; Cardoso, V.N.; Diniz, O.F.

    2015-01-01

    Osteomyelitis, which is characterized by progressive inflammatory destruction and new opposition of bone, is still a difficult infection to treat. The clinical diagnosis in late stages is achieved easily, but an early diagnosis is more challenging. Staphylococcus aureus is a common agent found in osteomyelitis and bone prostheses infection. Diagnosis by scintigraphy has advantages because it is a non-invasive procedure and is able to perform an early diagnosis even before anatomic changes. Thus, nuclear medicine could contribute to an accurate diagnosis since specific radiopharmaceuticals were developed. In this study, aptamers selected to Staphylococcus aureus were labeled with 99m Tc and used for bacteria identification in an osteomyelitis experimental model. The aptamers selected to S. aureus were directly labelled with 99m Tc and were evaluated by biodistribution studies. Wistar rats with intraosseous infection in the right paw were used. A random aptamer labelled with 99m Tc was as control. Six animals were used in each group. The aptamers labeled with 99m Tc were able to identify the infection foci caused by S. aureus displaying a target/non-target ratio of 2,23 ± 0,20, after 3 h. The control group presented a target/non-target ratio 1,08 ± 0.23. The results indicated that the radiolabeled aptamers were able to identify specifically the infection foci and they should be further explored for infection diagnosis by scintigraphy. (author)

  11. Clinical experience in humans with radiolabeled antibody for tumor detection

    International Nuclear Information System (INIS)

    Morrison, R.T.; Lyster, D.M.; Szasz, I.; Alcorn, L.N.; Huckell, V.F.; Rhodes, B.; Breslow, K.; Burchiel, S.

    1982-01-01

    I-131 and Tc-99m labeled polyclonal or monoclonal antibody and fragments of antibody, specific to human chorionic gonadotropin (hCG) or to a melanoma cell surface antigen (MCSA) were injected into proven cancer patients. Using standard homeostasis parameters, and scanning techniques, the safety and efficacy of each antibody was evaluated. Antibody fragments were expected to clear faster from the circulation allowing for earlier imaging and a better target-to-non-target ratio. The technetium label may perturb the antiboby's kinetics so that clearance is more rapid for both whole antibody and fragments. After a statistical evaluation of all parameters measured pre and post injection it was concluded that no acute toxicity reactions were present in any patient studied. Scan results were not acceptable for a tumor detecting procedure used in routine practice. Tumor upake was seen in less than 10% of scans

  12. Comparison of endogenous and radiolabeled bile acid excretion in patients with idiopathic chronic diarrhea

    International Nuclear Information System (INIS)

    Schiller, L.R.; Bilhartz, L.E.; Santa Ana, C.A.

    1990-01-01

    Fecal recovery of radioactivity after ingestion of a bolus of radiolabeled bile acid is abnormally high in most patients with idiopathic chronic diarrhea. To evaluate the significance of this malabsorption, concurrent fecal excretion of both exogenous radiolabeled bile acid and endogenous (unlabeled) bile acid were measured in patients with idiopathic chronic diarrhea. Subjects received a 2.5-microCi oral dose of taurocholic acid labeled with 14C in the 24th position of the steroid moiety. Endogenous bile acid excretion was measured by a hydroxysteroid dehydrogenase assay on a concurrent 72-h stool collection. Both radiolabeled and endogenous bile acid excretion were abnormally high in most patients with chronic diarrhea compared with normal subjects, even when equivoluminous diarrhea was induced in normal subjects by ingestion of osmotically active solutions. The correlation between radiolabeled and endogenous bile acid excretion was good. However, neither radiolabeled nor endogenous bile acid excretion was as abnormal as is typically seen in patients with ileal resection, and none of these diarrhea patients responded to treatment with cholestyramine with stool weights less than 200 g. These results suggest (a) that this radiolabeled bile acid excretion test accurately reflects excess endogenous bile acid excretion; (b) that excess endogenous bile acid excretion is not caused by diarrhea per se; (c) that spontaneously occurring idiopathic chronic diarrhea is often associated with increased endogenous bile acid excretion; and (d) that bile acid malabsorption is not likely to be the primary cause of diarrhea in most of these patients

  13. In vitro incorporation of radiolabeled cholesteryl esters into high and low density lipoproteins

    International Nuclear Information System (INIS)

    Terpstra, A.H.; Nicolosi, R.J.; Herbert, P.N.

    1989-01-01

    We have developed and validated a method for in vitro incorporation of radiolabeled cholesteryl esters into low density (LDL) and high density lipoproteins (HDL). Radiolabeled cholesteryl esters dissolved in absolute ethanol were mixed with LDL or HDL in the presence of lipoprotein-deficient serum (LPDS) as a source of core lipid transfer activity. The efficiency of incorporation was dependent on: (a) the core lipid transfer activity and quantity of LPDS, (b) the mass of added radiolabeled cholesteryl esters, (c) the length of incubation, and (d) the amount of acceptor lipoprotein cholesterol. The tracer incorporation was documented by repeat density gradient ultracentrifugation, agarose gel electrophoresis, and precipitation with heparin-MnCl2. The radiolabeling conditions did not affect the following properties of the lipoproteins: (1) chemical composition, (2) electrophoretic mobility on agarose gels, (3) hydrated density, (4) distribution of apoproteins on SDS gels, (5) plasma clearance rates, and (6) immunoprecipitability of HDL apoproteins A-I and A-II. Rat HDL containing radiolabeled cholesteryl esters incorporated in vitro had plasma disappearance rates identical to HDL radiolabeled in vivo

  14. Imaging with radiolabelled anti-membrane type 1 matrix metalloproteinase (MT1-MMP) antibody: potentials for characterizing atherosclerotic plaques

    Energy Technology Data Exchange (ETDEWEB)

    Kuge, Yuji [Kyoto University, Department of Patho-functional Bioanalysis, Graduate School of Pharmaceutical Sciences, Kyoto (Japan); Hokkaido University, Department of Tracer Kinetics and Bioanalysis, Graduate School of Medicine, Sapporo (Japan); Hokkaido University, Central Institute of Isotope Science, Sapporo (Japan); Takai, Nozomi; Ogawa, Yuki; Temma, Takashi; Nishigori, Kantaro; Ishino, Seigo; Kamihashi, Junko; Saji, Hideo [Kyoto University, Department of Patho-functional Bioanalysis, Graduate School of Pharmaceutical Sciences, Kyoto (Japan); Zhao, Yan [Hokkaido University, Department of Tracer Kinetics and Bioanalysis, Graduate School of Medicine, Sapporo (Japan); Kiyono, Yasushi [Kyoto University, Department of Patho-functional Bioanalysis, Graduate School of Pharmaceutical Sciences, Kyoto (Japan); University of Fukui, Biomedical Imaging Research Center, Fukui (Japan); Shiomi, Masashi [Kobe University Graduate School of Medicine, Institute for Experimental Animals, Kobe (Japan)

    2010-11-15

    Membrane type 1 matrix metalloproteinase (MT1-MMP) activates pro-MMP-2 and pro-MMP-13 to their active forms and plays important roles in the destabilization of atherosclerotic plaques. This study sought to determine the usefulness of {sup 99m}Tc-labelled monoclonal antibody (mAb), recognizing MT1-MMP, for imaging atherosclerosis in a rabbit model (WHHLMI rabbits). Anti-MT1-MMP monoclonal IgG{sub 3} and negative control IgG{sub 3} were radiolabelled with {sup 99m}Tc after derivatization with 6-hydrazinonicotinic acid (HYNIC) to yield {sup 99m}Tc-MT1-MMP mAb and {sup 99m}Tc-IgG{sub 3}, respectively. WHHLMI and control rabbits were injected with these radio-probes. The aorta was removed and radioactivity was measured at 24 h after the injection. Autoradiography and histological studies were performed. {sup 99m}Tc-MT1-MMP mAb accumulation in WHHLMI rabbit aortas was 5.4-fold higher than that of control rabbits. Regional {sup 99m}Tc-MT1-MMP mAb accumulation was positively correlated with MT1-MMP expression (r = 0.59, p < 0.0001), while {sup 99m}Tc-IgG{sub 3} accumulation was independent of MT1-MMP expression (r = 0.03, p = NS). The highest {sup 99m}Tc-MT1-MMP mAb accumulation was found in atheromatous lesions (4.8 {+-} 1.9, %ID x BW/mm{sup 2} x 10{sup 2}), followed in decreasing order by fibroatheromatous (1.8 {+-} 1.3), collagen-rich (1.6 {+-} 1.0) and neointimal lesions (1.5 {+-} 1.5). In contrast, {sup 99m}Tc-IgG{sub 3} accumulation was almost independent of the histological grade of lesions. Higher {sup 99m}Tc-MT1-MMP mAb accumulation in grade IV atheroma was shown in comparison with neointimal lesions or other more stable lesions. Nuclear imaging with {sup 99m}Tc-MT1-MMP mAb, in combination with CT and MRI, could provide new diagnostic imaging capabilities for detecting vulnerable plaques, although further investigations to improve target to blood ratios are strongly required. (orig.)

  15. Imaging with radiolabelled anti-membrane type 1 matrix metalloproteinase (MT1-MMP) antibody: potentials for characterizing atherosclerotic plaques

    International Nuclear Information System (INIS)

    Kuge, Yuji; Takai, Nozomi; Ogawa, Yuki; Temma, Takashi; Nishigori, Kantaro; Ishino, Seigo; Kamihashi, Junko; Saji, Hideo; Zhao, Yan; Kiyono, Yasushi; Shiomi, Masashi

    2010-01-01

    Membrane type 1 matrix metalloproteinase (MT1-MMP) activates pro-MMP-2 and pro-MMP-13 to their active forms and plays important roles in the destabilization of atherosclerotic plaques. This study sought to determine the usefulness of 99m Tc-labelled monoclonal antibody (mAb), recognizing MT1-MMP, for imaging atherosclerosis in a rabbit model (WHHLMI rabbits). Anti-MT1-MMP monoclonal IgG 3 and negative control IgG 3 were radiolabelled with 99m Tc after derivatization with 6-hydrazinonicotinic acid (HYNIC) to yield 99m Tc-MT1-MMP mAb and 99m Tc-IgG 3 , respectively. WHHLMI and control rabbits were injected with these radio-probes. The aorta was removed and radioactivity was measured at 24 h after the injection. Autoradiography and histological studies were performed. 99m Tc-MT1-MMP mAb accumulation in WHHLMI rabbit aortas was 5.4-fold higher than that of control rabbits. Regional 99m Tc-MT1-MMP mAb accumulation was positively correlated with MT1-MMP expression (r = 0.59, p 99m Tc-IgG 3 accumulation was independent of MT1-MMP expression (r = 0.03, p = NS). The highest 99m Tc-MT1-MMP mAb accumulation was found in atheromatous lesions (4.8 ± 1.9, %ID x BW/mm 2 x 10 2 ), followed in decreasing order by fibroatheromatous (1.8 ± 1.3), collagen-rich (1.6 ± 1.0) and neointimal lesions (1.5 ± 1.5). In contrast, 99m Tc-IgG 3 accumulation was almost independent of the histological grade of lesions. Higher 99m Tc-MT1-MMP mAb accumulation in grade IV atheroma was shown in comparison with neointimal lesions or other more stable lesions. Nuclear imaging with 99m Tc-MT1-MMP mAb, in combination with CT and MRI, could provide new diagnostic imaging capabilities for detecting vulnerable plaques, although further investigations to improve target to blood ratios are strongly required. (orig.)

  16. Pharmacokinetics of radiolabelled anti-fibrin MAb DD-3B6/22 and factors effecting its localization to thrombi

    International Nuclear Information System (INIS)

    Boniface, G.R.; Lee, F.T.; Milner, L.J.; Walker, K.Z.

    1990-01-01

    The monoclonal antibody DD-3B6/22 recognizes the D-dimer (DD) epitope of human cross-linked fibrin and is currently being investigated as a potential thrombosis imaging agent. The pharmacokinetic profiles of 99m Tc labelled intact and Fab' fragments of DD-3B6/22 were determined in rabbits and gave whole body clearance estimates of 0.06 ± 0.01 and 1.61 ± 0.24 mL/min/kg respectively. The effect of heparin, radiological contrast media and free DD antigen levels on in vitro binding of 99m Tc-DD-3B6/22 Fab' was determined by inhibition assays to immobilized antigen and human clots. No effect on binding was demonstrated with heparin or contrast media at clinically significant concentrations. DD supernata concentrations of between 8-20 μg/mL were required to inhibit the in vitro binding 99m Tc-DD-3B6/22 Fab' to immobilized antigen or blood clot by 50%. Localisation studies of 99m Tc-DD-3B6/22 Fab' in a rabbit jugular vein clot model were carried out in animals co-administered free DD antigen. Results indicated minimal inhibition of 99m Tc-DD-3B6/22 Fab' clot localization after 4 hours up to a level of 16 μg/mL DD plasma concentration. These results suggest that thrombosis imaging with radiolabelled DD-3B6/22 should be unduly affected by the co-administration of heparin or venographic contrast media in the clinical setting, whilst free antigen effect should not occur within clinically relevant titres. 21 refs., 2 tabs., 4 figs

  17. Antitumor activity of Annona squamosa seed oil.

    Science.gov (United States)

    Chen, Yong; Chen, Yayun; Shi, Yeye; Ma, Chengyao; Wang, Xunan; Li, Yue; Miao, Yunjie; Chen, Jianwei; Li, Xiang

    2016-12-04

    Custard apple (Annona squamosa Linn.) is an edible tropical fruit, and its seeds have been used to treat "malignant sore" (cancer) and other usage as insecticide. A comparison of extraction processes, chemical composition analysis and antitumor activity of A. squamosa seed oil (ASO) were investigated. The optimal extraction parameters of ASO were established by comparing percolation, soxhlet, ultrasonic and SFE-CO 2 extraction methods. The chemical composition of fatty acid and content of total annonaceous acetogenins (ACGs) of ASO was investigated by GC-MS and colorimetric assay, and anti-tumor activity of ASO was tested using H 22 xenografts bearing mice. The optimal extraction parameters of ASO were obtained as follows: using soxhlet extraction method with extraction solvent of petroleum ether, temperature of 80°C, and extraction time of 90min. Under these conditions, the yield of ASO was 22.65%. GC-MS analysis results showed that the main chemical compositions of fatty acid of ASO were palmitic acid (9.92%), linoleic acid (20.49%), oleic acid (56.50%) and stearic acid (9.14%). The total ACGs content in ASO was 41.00mg/g. ASO inhibited the growth of H 22 tumor cells in mice with a maximum inhibitory rate of 53.54% by oral administration. Furthermore, it was found that ASO exerted an antitumor effect via decreasing interleukin-6 (IL-6), janus kinase (Jak) and phosphorylated signal transducers and activators of transcription (p-Stat3) expression. The results demonstrated that ASO suppressed the H 22 solid tumor development may due to its main chemical constituents unsaturated fatty acid and ACGs via IL-6/Jak/Stat3 pathway. ASO may be a potential candidate for the treatment of cancer. Copyright © 2016 Elsevier Ireland Ltd. All rights reserved.

  18. Analyses of the peripheral immunome following multiple administrations of avelumab, a human IgG1 anti-PD-L1 monoclonal antibody

    OpenAIRE

    Donahue, Renee N.; Lepone, Lauren M.; Grenga, Italia; Jochems, Caroline; Fantini, Massimo; Madan, Ravi A.; Heery, Christopher R.; Gulley, James L.; Schlom, Jeffrey

    2017-01-01

    Background Multiple anti-PD-L1/PD-1 checkpoint monoclonal antibodies (MAb) have shown clear evidence of clinical benefit. All except one have been designed or engineered to omit the possibility to mediate antibody-dependent cell-mediated cytotoxicity (ADCC) as a second potential mode of anti-tumor activity; the reason for this is the concern of lysis of PD-L1 positive immune cells. Avelumab is a fully human IgG1 MAb which has been shown in prior in vitro studies to mediate ADCC versus a range...

  19. Radioimmunoimaging using F(ab')2 fragment of monoclonal antibodies against human alpha-fetoprotein

    International Nuclear Information System (INIS)

    Sakahara, Harumi; Endo, Keigo; Nakashima, Tetsuo; Koizumi, Mitsuru; Ohta, Hitoya; Torizuka, Kanji; Okada, Kenichiro; Yoshida, Osamu; Nishi, Shinzo.

    1985-01-01

    Using monoclonal antibodies against human α-fetoprotein (AFP), radioiodinated F(ab') 2 fragments were compared with whole IgG as a radiotracer for radioimmunoimaging of cancer. F(ab') 2 fragments were obtained by pepsin digestion of whole IgG (IgGl). IgG and F(ab') 2 were labeled with 125 I or 131 I by the chloramine-T method with almost full retention of antibody activity. F(ab') 2 fragments were cleared more rapidly from the circulation in normal mice with a half life of 6.3 hours than whole IgG with a half life of 5.5 days. Radioactivity of F(ab') 2 in various organs also decreased faster than IgG. In nude mice transplanted with AFP-producing human testicular tumor, F(ab') 2 fragments demonstrated superior scintigrams to whole IgG at 2 days after the injection, because of the fast disappearance of background radioactivity. Although absolute accumulation of 131 I labeled F(ab') 2 in the tumor was less than that of 131 I labeled IgG, tumor to other organ ratios were much higher with F(ab') 2 than those of IgG. The tumor to blood ratio of 131 I labeled F(ab') 2 was 1.04 at day 2, whereas tumor to blood ratio of 131 I labeled IgG was 0.55 at day 2 and 0.92 at day 4, respectively. These results indicated that for the radiolabeling of monoclonal antibodies, F(ab') 2 fragments would be superior to whole IgG in the radioimmunoimaging of cancer. (author)

  20. The processing and fate of antibodies and their radiolabels bound to the surface of tumor cells in vitro: A comparison of nine radiolabels

    International Nuclear Information System (INIS)

    Shih, L.B.; Thorpe, S.R.; Griffiths, G.L.; Diril, H.; Ong, G.L.; Hansen, H.J.; Goldenberg, D.M.; Mattes, M.J.

    1994-01-01

    Processing radiolabeled degradation products is the key factor affecting retention of antibodies within the cell. In this study, the authors have analyzed the processing of antibodies labeled in nine different ways. Antibodies were labeled with three different radioisotopes and seven different forms of 125 I. Eight of the radiolabels (except 188 Re) were conjugated to the same antibody, MA103, and tested on the renal carcinoma cell line SK-RC-18 and/or the ovarian carcinoma cell line SK-OV-6. Rhenium conjugation utilized the antibody RS7, the target cell line ME180 and three of the other radiolabels were also tested with this antibody-target cell combination for comparison. Iodine conjugated to antibodies by conventional methods was rapidly released from the cell after antibody catabolism. In contrast, iodinated moieties, such as dilactitol-tyramine and inulin-tyramine were retained within cells four to five times longer. The use of radiolabels that are trapped within cells after antibody catabolism can potentially increase the dose of radiation delivered to the tumor, from the same amount of radioactivity deposited by a factor of four or five. The prolonged retention of 111 In relative to 125 I is not due to deiodination of iodine conjugates, but rather to intracellular retention of catabolic products containing 111 In, perhaps within lysosomes. 45 refs., 4 figs., 1 tab

  1. Radiolabeling, characterization and preliminary studies of 90Y-octreotate

    International Nuclear Information System (INIS)

    Klementyeva, O.E.; Bruskin, A.B.; Larenkov, A.A.; Kodina, G.E.; Korsunsky, V.N.

    2015-01-01

    Full text of publication follows. Introduction: Overexpression of the somatostatin receptors in neuroendocrine tumors has become the molecular basis for the use of somatostatin analogues in diagnosis and therapy for these neoplasms. The high energy (maximum 2.2 MeV) and penetration range (R 95 5.7 mm) of β-particles from 90 Y are advantageous, with a direct killing of somatostatin receptor positive cells and a crossfire effect which hits nearby receptor-negative tumour cells [Ref. 1]. Aim: the investigation of the reaction conditions for the preparation of 90 Y-Octreotate and its in vitro characterization. Materials and methods: DOTA-Octreotate (Farm-Syntez Ltd.) and 88 YCl 3 (V/O Isotop) were used without purification. 88 Y-Octreotate was prepared in acetate buffer solution and its radiochemical purity was controlled by ITLC. In-vitro experiments were carried out with melanoma B16. Studies of internalization were performed as described in [Ref. 2]. Results: the maximal accumulation in the cells was observed after 90 min from the beginning of incubation and was about 3.9%. In our experiments, we found high level of internalization of the surface-bound 88 Y-Octreotate into B16 cells. Maximal internalization level was 80% after 60 min of incubation. Conclusion: the optimal conditions for effective labeling (> 95%) of DOTA-Octreotate were found. The results obtained using the gamma-emitting 88 Y, provide a basis for in vivo research 90 Y octreotate as radiotherapeutic agent. References: [Ref. 1] Bodei, L.; Pepe, G.; Paganelli, G.; Peptide receptor radionuclide therapy (PRRT) of neuroendocrine tumors with somatostatin analogues. Eur. Rev. Med. Pharmacol. Sci., 2010; v. 14: 347-351. [Ref. 2] Garcia Garayoa E., Allemann-Tannahill L., et al. In vitro and in vivo evaluation of new radiolabeled neurotensin (8-13) analogs with high affinity for NT1 receptors. Nucl. Med. Biol. 2001; 28: 75-84. (authors)

  2. In vitro evaluation of radiolabeled aptamers for colon carcinoma diagnosis

    Energy Technology Data Exchange (ETDEWEB)

    Correa, C.R.; Ferreira, I.M; Santos, S.R.; Faria, L.S.; Andrade, A.S.R., E-mail: crisrcorrea@gmail.com, E-mail: antero@cdtn.br [Centro de Desenvolvimento da Tecnologia Nuclear (CDTN/CNEN-MG), Belo Horizonte, MG (Brazil); Goes, A.M., E-mail: goes@icb.ufmg.br [Universidade Federal de Minas Gerais (UFMG), Belo Horizonte, MG (Brazil). Inst. de Ciencias Biologicas. Dept. de Imunologia e Bioquimica

    2013-07-01

    Cancer is a leading cause of death worldwide, representing a major public health problem worldwide. Colorectal cancers accounts around 8% of all deaths for cancer in 2008, is the fourth most lethal. Many colorectal cancer markers, such as carcinoembryonic antigen (CEA), A33, and CSA-p, have been studied as the therapeutic targets in preclinical or clinical settings. CEA is a complex intracellular glycoprotein produced by about 90% of colorectal cancers. Since its discovery in 1965, a very large number of studies have been carried out to determine the effectiveness of CEA as clinically useful tumor markers. Aptamers are short single-stranded nucleic acid oligomers (DNA or RNA) that can form specific and complex three-dimensional structures which can bind with high affinity to specific targets, they are functionally equivalent of antibodies. Aptamers have the advantage of being highly specific, relatively small size, and non-immunogenic. The aim of this study was develop anti-CEA aptamers for use as imaging agents. The aptamers are obtained through by SELEX (systematic evolution of ligands by exponential enrichment), in which aptamers are selected from a library of random sequences of synthetic DNA by repetitive binding of the oligonucleotides to target molecule. These aptamers were confirmed to have affinity and specific binding for T84 cell line (target cell), showed by fluorescence microscopic images. Individual aptamers sequences that bound T84 cells were {sup 32}P-radiolabeled and incubated at different concentrations on cell monolayers, to monitor the aptamers affinity binding. The selected aptamers can identify colon cancer cell line. This aptamers could be further developed for early disease detection as radiopharmaceuticals, as well as prognostic markers, of colorectal cancers. (author)

  3. In vitro evaluation of radiolabeled aptamers for colon carcinoma diagnosis

    International Nuclear Information System (INIS)

    Correa, C.R.; Ferreira, I.M; Santos, S.R.; Faria, L.S.; Andrade, A.S.R.; Goes, A.M.

    2013-01-01

    Cancer is a leading cause of death worldwide, representing a major public health problem worldwide. Colorectal cancers accounts around 8% of all deaths for cancer in 2008, is the fourth most lethal. Many colorectal cancer markers, such as carcinoembryonic antigen (CEA), A33, and CSA-p, have been studied as the therapeutic targets in preclinical or clinical settings. CEA is a complex intracellular glycoprotein produced by about 90% of colorectal cancers. Since its discovery in 1965, a very large number of studies have been carried out to determine the effectiveness of CEA as clinically useful tumor markers. Aptamers are short single-stranded nucleic acid oligomers (DNA or RNA) that can form specific and complex three-dimensional structures which can bind with high affinity to specific targets, they are functionally equivalent of antibodies. Aptamers have the advantage of being highly specific, relatively small size, and non-immunogenic. The aim of this study was develop anti-CEA aptamers for use as imaging agents. The aptamers are obtained through by SELEX (systematic evolution of ligands by exponential enrichment), in which aptamers are selected from a library of random sequences of synthetic DNA by repetitive binding of the oligonucleotides to target molecule. These aptamers were confirmed to have affinity and specific binding for T84 cell line (target cell), showed by fluorescence microscopic images. Individual aptamers sequences that bound T84 cells were 32 P-radiolabeled and incubated at different concentrations on cell monolayers, to monitor the aptamers affinity binding. The selected aptamers can identify colon cancer cell line. This aptamers could be further developed for early disease detection as radiopharmaceuticals, as well as prognostic markers, of colorectal cancers. (author)

  4. Technetium-99 labelling of DD-3B6/22 antifibrin monoclonal antibody fragmented Fab' for thrombus imaging

    International Nuclear Information System (INIS)

    Lee, F-T.; Boniface, G.R.; Lambrecht, R.M.; Rylatt, D.B.; Bundesen, P.G.

    1993-01-01

    The antifibrin DD-3B6/22 monoclonal antibody Fab' fragment, a murine immunoglobulin, IgG3, has been labelled with technetium-99m ( 99mTc ) via a transchelation reaction, to specific activity in excess of 30 mCi/mg protein. The radiolabelling of Fab' was dependent on time, temperature, pH, antibody concentrations and nature intermediary transchelation complex used. The resultant radioconjugate was stable in vitro and in vivo. Blood clearance of 99m Tc-Fab' in rat followed two compartment kinetics with the half time of the fast phase being 0.5 h. The main route of excretion was via the kidneys with little uptake indicated by other tissues. The results suggest that the inherent specificity of the antibody, small molecular size, rapid plasma clearance, high specific radioactivity, together with the physical properties of the 99m Tc label, combine to make this labelled monoclonal antibody (MoAb), potentially suitable as a radiopharmaceutical for the scintigraphic detection of thrombi in humans. 17 refs., 3 tabs., 5 figs

  5. [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.

  6. 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

  7. 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.

  8. Radiolabeled Antibody Fragment for Preparation of (177Lu-DOTAm-PAMAM G3.0-F(ab’2 trastuzumab as a Radiopharmaceutical for Cancer Therapy

    Directory of Open Access Journals (Sweden)

    R.D. Haryuni

    2017-06-01

    Full Text Available Several radiolabeled monoclonal antibodies (mAbs have been used as radioimmunotherapy (RIT agents for cancer therapy. The use of mAbs as RIT agents is due to their ability to carry effectors, in the form of radionuclides which emit alpha (α particles, beta (β particles, or auger electrons, and bind specifically to cancer expressed receptor. This paper reports the preparation of radiolabelled trastuzumab in form of (177Lu-DOTAm-PAMAM G3-F(ab'2-trastuzumab, which will be expected as a potential RIT agent for therapy of breast cancer overexpressed human epidermal growth factor receptor 2 (HER2. Due to its reduced molecular weight, the use of F(ab'2-trastuzumab on the aforementioned RIT agent candidate is expected to reach its target much faster compared to the intact trastuzumab. Meanwhile, the role of PAMAM G3 is to increase the specific activity of the radiotherapeutic agent of Lu-177 due to the ability of its 32 –NH2 functional groups that are able to bind many DOTAs (£ 31 which in turn can bind a large number of 177Lu. The preparation was initiated by fragmentation of trastuzumab using pepsin enzyme in 0.02 M acetic acid buffer with a pH of 4.5 to produce F(ab'2-trastuzumab with a purity of 95 % after purification with PD-10 column. The F(ab'2-trastuzumab was then reacted with succinimidyl 4-(N-maleimidomethyl cyclohexane-1-carboxylate (SMCC to produce SMCC-F(ab'2-trastuzumab. The next reaction was to conjugate SMCC-F(ab'2-trastuzumab with DOTA-PAMAM G3.0-SH, which was prepared by reaction NHS-DOTA with PAMAM G3.0 and followed by reacting it with 2-iminothiolane to give (DOTAm-PAMAM G3.0-F(ab'2-trastuzumab. Finally, the (DOTAm-PAMAM G3.0-F(ab'2-trastuzumab was radiolabelled with 177Lu to produce (177Lu-DOTAm-PAMAM G3.0-F(ab'2-trastuzumab, resulting in a radiochemical purity of 98 % after purification with PD-10 column.Received: 31 October 2015; Revised: 30 June 2016; Accepted: 25 September 2016

  9. 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

  10. 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.

  11. Anti-tumor effect of polysaccharides from rhizome of Curculigo ...

    African Journals Online (AJOL)

    The anti-tumor effect of PDC on cervical cancer was investigated in vivo in mice injected with Hela cells. The parameters measured were tumor volume and weight. In vitro anti-tumor effects of PDC were assessed by measuring expressions of caspase-3, caspase-9 and P53 proteins in Hela cells via ELISA assay. Thymus ...

  12. Smart Mesoporous Nanomaterials for Antitumor Therapy

    Directory of Open Access Journals (Sweden)

    Marina Martínez-Carmona

    2015-11-01

    Full Text Available The use of nanomaterials for the treatment of solid tumours is receiving increasing attention by the scientific community. Among them, mesoporous silica nanoparticles (MSNs exhibit unique features that make them suitable nanocarriers to host, transport and protect drug molecules until the target is reached. It is possible to incorporate different targeting ligands to the outermost surface of MSNs to selectively drive the drugs to the tumour tissues. To prevent the premature release of the cargo entrapped in the mesopores, it is feasible to cap the pore entrances using stimuli-responsive nanogates. Therefore, upon exposure to internal (pH, enzymes, glutathione, etc. or external (temperature, light, magnetic field, etc. stimuli, the pore opening takes place and the release of the entrapped cargo occurs. These smart MSNs are capable of selectively reaching and accumulating at the target tissue and releasing the entrapped drug in a specific and controlled fashion, constituting a promising alternative to conventional chemotherapy, which is typically associated with undesired side effects. In this review, we overview the recent advances reported by the scientific community in developing MSNs for antitumor therapy. We highlight the possibility to design multifunctional nanosystems using different therapeutic approaches aimed at increasing the efficacy of the antitumor treatment.

  13. Induction of antitumor immunity through xenoplacental immunization

    Directory of Open Access Journals (Sweden)

    Agadjanyan Michael G

    2006-05-01

    Full Text Available Abstract Historically cancer vaccines have yielded suboptimal clinical results. We have developed a novel strategy for eliciting antitumor immunity based upon homology between neoplastic tissue and the developing placenta. Placenta formation shares several key processes with neoplasia, namely: angiogenesis, activation of matrix metalloproteases, and active suppression of immune function. Immune responses against xenoantigens are well known to break self-tolerance. Utilizing xenogeneic placental protein extracts as a vaccine, we have successfully induced anti-tumor immunity against B16 melanoma in C57/BL6 mice, whereas control xenogeneic extracts and B16 tumor extracts where ineffective, or actually promoted tumor growth, respectively. Furthermore, dendritic cells were able to prime tumor immunity when pulsed with the placental xenoantigens. While vaccination-induced tumor regression was abolished in mice depleted of CD4 T cells, both CD4 and CD8 cells were needed to adoptively transfer immunity to naïve mice. Supporting the role of CD8 cells in controlling tumor growth are findings that only freshly isolated CD8 cells from immunized mice were capable of inducing tumor cell caspases-3 activation ex vivo. These data suggest feasibility of using xenogeneic placental preparations as a multivalent vaccine potently targeting not just tumor antigens, but processes that are essential for tumor maintenance of malignant potential.

  14. Radiolabeling Silica-Based Nanoparticles via Coordination Chemistry: Basic Principles, Strategies, and Applications.

    Science.gov (United States)

    Ni, Dalong; Jiang, Dawei; Ehlerding, Emily B; Huang, Peng; Cai, Weibo

    2018-03-20

    As one of the most biocompatible and well-tolerated inorganic nanomaterials, silica-based nanoparticles (SiNPs) have received extensive attention over the last several decades. Recently, positron emission tomography (PET) imaging of radiolabeled SiNPs has provided a highly sensitive, noninvasive, and quantitative readout of the organ/tissue distribution, pharmacokinetics, and tumor targeting efficiency in vivo, which can greatly expedite the clinical translation of these promising NPs. Encouraged by the successful PET imaging of patients with metastatic melanoma using 124 I-labeled ultrasmall SiNPs (known as Cornell dots or C dots) and their approval as an Investigational New Drug (IND) by the United States Food and Drug Administration, different radioisotopes ( 64 Cu, 89 Zr, 18 F, 68 Ga, 124 I, etc.) have been reported to radiolabel a wide variety of SiNPs-based nanostructures, including dense silica (dSiO 2 ), mesoporous silica (MSN), biodegradable mesoporous silica (bMSN), and hollow mesoporous silica nanoparticles (HMSN). With in-depth knowledge of coordination chemistry, abundant silanol groups (-Si-O-) on the silica surface or inside mesoporous channels not only can be directly used for chelator-free radiolabeling but also can be readily modified with the right chelators for chelator-based labeling. However, integrating these labeling strategies for constructing stably radiolabeled SiNPs with high efficiency has proven difficult because of the complexity of the involved key parameters, such as the choice of radioisotopes and chelators, nanostructures, and radiolabeling strategy. In this Account, we present an overview of recent progress in the development of radiolabeled SiNPs for cancer theranostics in the hope of speeding up their biomedical applications and potential translation into the clinic. We first introduce the basic principles and mechanisms for radiolabeling SiNPs via coordination chemistry, including general rules of selecting proper

  15. Studies of monoclonal antibodies IOR-CEA-1 and IOR-EGF/R3 labelled with 99mTc

    International Nuclear Information System (INIS)

    Dias, Carla Roberta de Barros Rodrigues

    2005-01-01

    Nuclear Medicine is a speciality that uses radioisotopes for the diagnosis or treatment of diseases and it is considered one of the best tools among the diagnostic modalities for detection of cancer. 99m Tc is one of the main isotopes for labelling antibodies and in Nuclear Medicine in general, due to its adequate physical properties, availability and low cost. Labelled monoclonal antibodies have shown promising results for diagnosis and therapy of cancer and their use has brought great experimental and clinical advances in the field of oncology. The main clinical applications of immunoscintigraphy with monoclonal antibodies are staging and evaluation of tumoral reappearance. The antibodies employed in this work were: OIR-CEA-1, a murine monoclonal antibody that acts directly against CEA expressed in several neoplasia in particular those from the gastrointestinal tract (colorectal cancer) and IOR-EGF/R3, a murine monoclonal antibody that binds to the external domain of EGF-R and it has been used in the diagnosis of tumors of epithelial origin. The objectives of this work were the development and optimization of the reduction and purification processes, the radiolabelling techniques and quality control procedures (radiochemical, immunoreactivity and cystein challenge) and imaging studies of monoclonal antibodies OIR-CEA-1 and IOR-EGF/R3, using the simple, fast and efficient method of direct labelling of the antibody with 99m Tc. The final results was the definition of the best conditions for the preparation of lyophilized reactive kits of OIR-CEA-1 and IOR- EGF/R3 for an efficient diagnostic application in Nuclear Medicine. The most adequate conditions for the labelling of the antibodies were: 1.0 mg Ab, 29 μL MDP, 3.0 μg Sn 2+ , 1 mL of 99m Tc and 30 min. reaction time. With these conditions the labelling yield was always higher than 95% and the maximum activity of 99m Tc was about 2220 MBq (60 mCi). The evidences of the efficiency and quality of the methods here

  16. Production of interferon-gamma by in vivo tumor-sensitized T cells: Association with active antitumor immunity

    International Nuclear Information System (INIS)

    Bursuker, I.; Pearce, M.T.

    1990-01-01

    The state of active immunity to Meth A fibrosarcoma in mice immunized with an admixture of Meth A cells and Propionibacterium acnes is associated with possession by the host of spleen cells capable of producing interferon-gamma (IFN-gamma) upon in vitro restimulation with irradiated tumor cells. The ability of spleen cells from immunized mice to produce IFN-gamma in response to irradiated Meth A cells decays as active antitumor immunity is replaced by a state of immunological memory. The IFN-producing cells are L3T4+Ly2+, cyclophosphamide-sensitive and radiosensitive T cells, as determined by their sensitivity to corresponding monoclonal antibodies and complement. The induction of IFN-gamma production by in vivo tumor-sensitized T cells is tumor specific, in that spleen cells from mice immunized against Meth A fibrosarcoma can produce IFN in response to irradiated Meth A cells but not in response to another syngeneic tumor M109 lung carcinoma

  17. 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

  18. 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

  19. 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

  20. Detection of metastatic tumor in normal-sized retroperitoneal lymph nodes by monoclonal-antibody imaging

    International Nuclear Information System (INIS)

    Moldofsky, P.J.; Sears, H.F.; Mulhern, C.B. Jr.; Hammond, N.D.; Powe, J.; Gatenby, R.A.; Steplewski, Z.; Koprowski, H.

    1984-01-01

    Detection of metastatic colon carcinoma is reported in retroperitoneal lymph nodes that were visible but normal in size (less than 1 cm) and number on CT scanning and at surgery. A case history is presented of 1 of 27 patients with colon carcinoma, metastatic or primary, evaluated with intravenously administered, radiolabeled monoclonal-antibody fragments and subsequent nuclear medicine imaging. Images of /sup 99m/Tc-labeled red cells corresponding to each [ 131 I]antibody view of the abdomen were obtained as a control, to avoid interpretation of simple blood-pool radioactivity as specific localization of antibody on tumor. Antibody images were evaluated both without and with computer blood-pool image substraction. Directed to the level of the left renal hilum by the antibody scan, the surgeon removed the largest palpable node, which measured slightly less than 1 cm in diameter and was not palpably or visibly abnormal to the surgeon until it was removed and sectioned. Pathological evaluation of frozen and permanent sections revealed microscopic foci of adenocarcinoma consistent with a colonic primary tumor. Immunoperoxidase staining for the 1083-17-1A colorectal-carcinoma antigen demonstrated the presence of the antigen in the lymph node. As a result of the detection of this metastasis outside the liver, the patient did not receive the planned hepatic-artery chemotherapy pump but instead received intravenous chemotherapy

  1. Intraperitoneal delivery of monoclonal antibodies: enhanced regional delivery advantage using intravenous unlabeled anti-mouse antibody

    International Nuclear Information System (INIS)

    Wahl, R.L.; Fisher, S.

    1987-01-01

    Radiolabeled monoclonal antibodies (MAb) delivered intraperitoneally expose cells in contact with peritoneal fluid to considerably higher levels of MAb than if the MAb dose were given intravenously. This regional delivery advantage for intact MAb is present mainly due to the relatively slow exit of MAb from the peritoneal fluid to the blood. Eventually, following i.p. injection, blood levels of MAb rise resulting in exposure of the animal to high systemic MAb levels and potential toxicity. In this series of experiments, systemic exposure was minimized by the administration of unlabeled goat polyclonal anti-mouse antibody intravenously from 1 1/2 to 6 h following i.p. MAb injection. This maneuver results in the formation of immune complexes with their subsequent clearance and dehalogenation by the reticuloendothelial system, thus minimizing systemic MAb exposure. This approach, of increasing systemic clearance of MAb, did not alter intraperitoneal MAb levels and thus significantly increased the regional delivery advantage to the peritoneal cavity by 70-100%. This approach provides an immunologic rationale for the further enhancement of MAb delivery to i.p. foci of malignant disease and may have diagnostic and therapeutic utility. (author)

  2. Analysis of monoclonal antibodies reactive with molecules upregulated or expressed only on activated lymphocytes.

    Science.gov (United States)

    Davis, W C; Naessens, J; Brown, W C; Ellis, J A; Hamilton, M J; Cantor, G H; Barbosa, J I; Ferens, W; Bohach, G A

    1996-08-01

    Monoclonal antibodies potentially specific for antigens expressed or upregulated on activated leukocytes were selected for further analysis from the panel submitted to the third international workshop on ruminant leukocyte antigens. The kinetics of expression of these activation antigens on resting peripheral mononuclear cells (PBMC) and PBMC stimulated with concanavalin A or staphylococcal superantigen SECI for 4, 24 or 96 h were compared, as well as their appearance on various subsets of cells. For some of them, a molecular mass could be determined after immunoprecipitation from radio-labeled, lectin-stimulated cells. Based on the results from the clustering, kinetic studies and biochemical data, evidence was gathered for assigning two additional mAbs to cluster BoCD25 (IL-2 receptor) and two mAbs to cluster BoCD71 (transferrin receptor). Four mAbs recognized an early activation antigen predominantly expressed on gamma delta T cells in short-term cultures. A number of other activation antigens were further characterized.

  3. Radioimmunoscintigraphy with technetium-99m labelled monoclonal antibody, 1A3, in colorectal cancer

    International Nuclear Information System (INIS)

    Granowska, M.; Britton, K.E.; Mather, S.J.; Morris, G.; Ellison, D.; Soobramoney, S.; Talbot, I.C.; Northover, J.M.A.

    1993-01-01

    This study of radioimmunoscintigraphy (RIS) was primarily undertaken to determine how the imaging results related to surgical findings. Technetium-99m radiolabelled 1A3, a monoclonal antibody against a columnar cell surface antigen, was used. No adverse effects or thyroid uptake was observed in 127 studies. The 85 primary colorectal cancers were all image positive. In the assessment of recurrent tumour in the abdomen or pelvis, the accuracy was 33/35 (94%), including true-positive findings in some whose serum carcinoembryonic antigen was normal. There was a positive predictive value for abdominal or pelvic recurrence of 92% and a negative predictive value of 100%, at a prevalence of 66%. In those patients whose liver was able to be evaluated, the accuracy was 72/79 (91%). There was a positive predictive value for liver metastases of 88% and a negative predictive value of 93%, at a prelavence of 32%. The simple procedure for labelling antibody with 99m Tc and its ready availability allow a completed report to be given within 24 h of the request. (orig.)

  4. Monoclonal antibodies to the pretargeting approach: Developments in the radiopharmaceuticals for radioimmunotherapy

    International Nuclear Information System (INIS)

    Chinol, M.

    2001-01-01

    In recent years, large experience has been accrued through the clinical application of radiolabelled monoclonal antibodies in the diagnosis and therapy of malignant disorders. While radioimmunoscintigraphy has established its role in the nuclear medicine practice, radioimmunotherapy has thus far gained limited acceptance mainly due to the low amount of radioactivity that can be targeted to the tumour and to the myelotoxicity which is typically the dose limiting factor. In an attempt to overcome the low uptake of label by the tumour and improve the tumour-to-blood ratio, various studies have examined the concept of tumour pretargeting based on the separate protocols, especially the 3-step approach, with respect to the use of directly labelled antibodies, lies in the lower toxicity observed which has allowed to administer high doses of therapeutic radionuclides, such as Y-90, without bone marrow toxicity. Pilot studies, applied to the treatment of advanced stage tumours, have shown that this approach interferes with the progression of tumours and produce tumours regression in patients no longer responsive to other conventional therapeutic modalities. The potency of pretargeting based on the avidin/biotin system may be exploited in the near future to convey a variety of cytotoxic substances, other than radioactivity, onto cancer cells. (author)

  5. A computer program for quantification of SH groups generated after reduction of monoclonal antibodies

    International Nuclear Information System (INIS)

    Escobar, Normando Iznaga; Morales, Alejo; Nunez, Gilda

    1996-01-01

    Reduction of disulfide bonds to sulfhydryl (SH) groups for direct radiolabeling of antibodies for immunoscintigraphic studies of colorectal and other cancers continues to be of considerable research interest. We have developed a general strategy and a versatile computer program for the quantification of the number of SH per molecule of antibody (Ab) generated after the treatment of monoclonal antibodies (MAbs) with reducing agents such as 2-mercaptoethanol (2-ME), stannous chloride (SnCl 2 ), dithiothreitol (DTT), dithioerythritol (DTE), ascorbic acid (AA), and the like. The program we describe here performs an unweighted least-squares regression analysis of the cysteine standard curve and interpolates the cysteine concentration of the samples. The number of SH groups per molecule of antibody in the 2-mercaptoethanol and in the other reducing agents was calculated from the cysteine standard curve using Ellman's reagent to develop the yellow color. The linear least-squares method fit the standard data with a high degree of accuracy and with the correlation coefficient r of 0.999. A program has been written for the IBM PC compatible computer utilizing a friendly menu to interact with the users. The package allows the user to change parameters of the assay, to calculate regression coefficients slope, intercept and its standard errors, to perform statistical analysis, together with detailed analysis of variance, and to produce an output of the results in a printed format

  6. A computer program for quantification of SH groups generated after reduction of monoclonal antibodies

    Energy Technology Data Exchange (ETDEWEB)

    Escobar, Normando Iznaga; Morales, Alejo; Nunez, Gilda

    1996-07-01

    Reduction of disulfide bonds to sulfhydryl (SH) groups for direct radiolabeling of antibodies for immunoscintigraphic studies of colorectal and other cancers continues to be of considerable research interest. We have developed a general strategy and a versatile computer program for the quantification of the number of SH per molecule of antibody (Ab) generated after the treatment of monoclonal antibodies (MAbs) with reducing agents such as 2-mercaptoethanol (2-ME), stannous chloride (SnCl{sub 2}), dithiothreitol (DTT), dithioerythritol (DTE), ascorbic acid (AA), and the like. The program we describe here performs an unweighted least-squares regression analysis of the cysteine standard curve and interpolates the cysteine concentration of the samples. The number of SH groups per molecule of antibody in the 2-mercaptoethanol and in the other reducing agents was calculated from the cysteine standard curve using Ellman's reagent to develop the yellow color. The linear least-squares method fit the standard data with a high degree of accuracy and with the correlation coefficient r of 0.999. A program has been written for the IBM PC compatible computer utilizing a friendly menu to interact with the users. The package allows the user to change parameters of the assay, to calculate regression coefficients slope, intercept and its standard errors, to perform statistical analysis, together with detailed analysis of variance, and to produce an output of the results in a printed format.

  7. Pharmacokinetics of 111In-labeled anti-p97 monoclonal antibody in patients with metastatic malignant melanoma

    International Nuclear Information System (INIS)

    Rosenblum, M.G.; Murray, J.L.; Haynie, T.P.; Glenn, H.J.; Jahns, M.F.; Benjamin, R.S.; Frincke, J.M.; Carlo, D.J.; Hersh, E.M.

    1985-01-01

    Twenty-eight patients with metastatic malignant melanoma received anti-p97 murine monoclonal antibody (96.5) infused over 2 h at doses between 1 and 20 mg coupled to either 2.5 or 5.0 mCi of 111 In by the bifunctional chelating agent diethyltriaminepentaacetic acid. Clearance of 111 In from plasma closely fit an open, one-compartment mathematical model (r2 greater than 0.90). The overall half-life of 111 In plasma was approximately 31 h and did not appear to be dependent on the total dose of antibody administered. The apparent volume of distribution of the 111 In label approximated the total blood volume (7.8 +/- 0.7 liters) at the 1-mg dose and decreased to 3.0 +/- 0.14 liters at the 20-mg dose, suggesting saturation of antigenic or other extravascular binding sites at higher antibody doses. The clearance of the murine monoclonal antibody itself from plasma was measured by an enzyme-linked immunosorbent assay. The pharmacokinetics for the murine antibody in plasma also fit an open, one-compartment mathematical model. All pharmacokinetic parameters for unlabeled antibody closely paralleled those found for 111 In-labeled antibody pharmacokinetics. This suggests that the 111 In radiolabel remains complexed to the monoclonal antibody after in vivo administration. The cumulative urinary excretion of the 111 In label over 48 h was between 12 and 23% of the total administered dose and is assumed to represent 111 In-labeled chelate complex unattached to antibody. Analysis of the 111 In label in spleen, liver, heart, and kidney showed that the concentration of label in liver tissue was reduced with increasing antibody doses and coincided with changes in the apparent volume of distribution

  8. Radiolabeling of anti-human prostatic specific membrane antigen antibody with 99Tcm and its biodistribution in nude mice bearing human prostate cancer

    International Nuclear Information System (INIS)

    Tu Shaohua; Shen Jiangfan; Tao Rong; Ji Xiaowen; Wang Yancheng

    2012-01-01

    Objective: To study the binding affinity of 99 Tc m labeled anti-human prostatic specific membrane antigen (PSMA) monoclonal antibody (McAb) J591 to prostate cancer cells and the biodistribution of 99 Tc m -J591 in nude mice bearing human prostate cancer. Methods: The McAb J591 was labeled with vTcm by improved Schwarz method and the labeled McAb was purified by Sephadex G-50. The binding affinity of J591 with prostate cancer cells was measured by Flow Cytometry. The nude mice bearing PSMA-positive C4-2 prostate carcinoma xenografts were served as experiment groups, mice with PSMA-negative pc3 tumors served as controls. The biodistribution of 99 Tc m -J591 were carried out in both model nude mice. Results: The radiolabeling efficiency of 99 Tc m -J591 was 78.9±6.2%, and radiochemical purity was more than 90% after purification. The 99 Tc m -J591 showed a good combination with PSMA-positive C4-2 cells and no combination with PSMA-negative PC3 cells in vitro. The biodistribution results showed that 99 Tcm-J591 was accumulated in tumor tissue during the 2-24 hours after injection in experiment groups, and no significant uptake in control group. The uptake of 99 Tcm-J591 in tumor tissue reached a maximum 15.91±5.16 % ID/g in experimental group at 12h post-injection. There was a significant difference compared with controls (P 0.05). Conclusion: The monoclonal antibody J591 exhibits an excellent immuno-reactivity and tumor targeting property, and it may be used in diagnosis and target therapy of prostate cancer. (authors)

  9. 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

  10. In vivo amyloid-β imaging in the APPPS1-21 transgenic mouse model with a 89Zr- labeled monoclonal antibody.

    Directory of Open Access Journals (Sweden)

    Ann-Marie eWaldron

    2016-03-01

    Full Text Available Introduction: The accumulation of amyloid-β is a pathological hallmark of Alzheimer’s disease and is a target for molecular imaging probes to aid in diagnosis and disease monitoring. This study evaluated the feasibility of using a radiolabeled monoclonal anti-amyloid-β antibody (JRF/AβN/25 to non-invasively assess amyloid-β burden in aged transgenic mice (APPPS1-21 with μPET imaging.Methods: We investigated the antibody JRF/AβN/25 that binds to full-length Aβ. JRF/AβN/25 was radiolabeled with a [89Zr]-desferal chelate and intravenously injected into 12-13 month aged APPPS1-21 mice and their wild-type (WT controls. Mice underwent in vivo μPET imaging at 2, 4 and 7 days post injection and were sacrificed at the end of each time point to assess brain penetrance, plaque labeling, biodistribution and tracer stability. To confirm imaging specificity we also evaluated brain uptake of a non-amyloid targeting [89Zr]-labeled antibody (Trastuzumab as a negative control, additionally we performed a competitive blocking study with non-radiolabeled Df-Bz-JRF/AβN/25 and finally we assessed the possible confounding effects of blood retention. Results: Voxel-wise analysis of μPET data demonstrated significant [89Zr]-Df-Bz-JRF/AβN/25 retention in APPPS1-21 mice at all time points investigated. With ex vivo measures of radioactivity, significantly higher retention of [89Zr]-Df-Bz-JRF/AβN/25 was found at 4 and 7 day pi in APPPS1-21 mice. Despite the observed genotypic differences, comparisons with immunohistochemistry revealed that in vivo plaque labeling was low. Furthermore, pre-treatment with Df-Bz-JRF/AβN/25 only partially blocked [89Zr]-Df-Bz-JRF/AβN/25 uptake indicative of a high contribution of non-specific binding. Conclusion: Amyloid plaques were detected in vivo with a radiolabeled monoclonal anti-amyloid antibody. The low brain penetrance of the antibodies in addition to non-specific binding prevented an accurate estimation of plaque

  11. 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...

  12. 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

  13. The human CD38 monoclonal antibody daratumumab shows antitumor activity and hampers leukemia-microenvironment interactions in chronic lymphocytic leukemia

    DEFF Research Database (Denmark)

    Matas-Céspedes, Alba; Vidal-Crespo, Anna; Rodriguez, Vanina

    2017-01-01

    Purpose: To establish a proof-of-concept for the efficacy of the anti-CD38 antibody daratumumab in the poor prognosis CD38+ chronic lymphocytic leukemia (CLL) subtype. Experimental Design: The mechanism of action of daratumumab was assessed in CLL primary cells and cell lines using peripheral blo...

  14. Assessment of radioactive residues arising from radiolabel instability in a multiple dose tissue distribution study in rats

    Energy Technology Data Exchange (ETDEWEB)

    Slatter, J.G. [Pharmacia Corp., Peapack, NJ (United States); Sams, J.P.; Easter, J.A. [Pharmacia Corp., Kalamazoo, MI (United States)] [and others

    2003-05-01

    Our study objectives were to quantitatively determine the effect of radiolabel instability on terminal phase radioactive tissue residues in a multiple dose tissue distribution study, to quantitatively compare tissue residue artifacts (non drug-related radioactivity) from two chemically-distinct radiolabel locations, and to conduct a definitive multiple dose tissue distribution study using the better of the two radiolabeled compounds. We compared the excretion and tissue distribution in rats of [{sup 14}C]linezolid, radiolabeled in two different locations, after 7 consecutive once daily [{sup 14}C] oral doses. The radiolabels were in the acetamide (two carbon) and oxazolidinone (isolated carbon) functional groups. Terminal phase tissue residue and excretion data were compared to data from rats dosed orally with [{sup 14}C]sodium acetate. Drug-related radioactivity was excreted rapidly over 24 h. After a single dose, the acetamide and oxazolidinone radiolabel sites both gave 3% of dose as exhaled {sup 14}CO{sub 2}. After 7 daily [{sup 14}C] oral doses, terminal phase radioactive tissue residues were higher from the acetamide radiolabel, relative to the oxazolidinone radiolabel, and were primarily not drug-related. In the definitive tissue distribution study, low concentrations of drug-related radioactivity in skin and thyroid were observed. We conclude that although small amounts of radiolabel instability do not significantly affect single dose tissue radioactivity C{sub max} and area under the curve (AUC), artifacts arising from radiolabel instability can prolong the apparent terminal phase half life and complicate study data interpretation. When possible, it is always preferable to use a completely stable radiolabel site. (author)

  15. Assessment of radioactive residues arising from radiolabel instability in a multiple dose tissue distribution study in rats

    International Nuclear Information System (INIS)

    Slatter, J.G.; Sams, J.P.; Easter, J.A.

    2003-01-01

    Our study objectives were to quantitatively determine the effect of radiolabel instability on terminal phase radioactive tissue residues in a multiple dose tissue distribution study, to quantitatively compare tissue residue artifacts (non drug-related radioactivity) from two chemically-distinct radiolabel locations, and to conduct a definitive multiple dose tissue distribution study using the better of the two radiolabeled compounds. We compared the excretion and tissue distribution in rats of [ 14 C]linezolid, radiolabeled in two different locations, after 7 consecutive once daily [ 14 C] oral doses. The radiolabels were in the acetamide (two carbon) and oxazolidinone (isolated carbon) functional groups. Terminal phase tissue residue and excretion data were compared to data from rats dosed orally with [ 14 C]sodium acetate. Drug-related radioactivity was excreted rapidly over 24 h. After a single dose, the acetamide and oxazolidinone radiolabel sites both gave 3% of dose as exhaled 14 CO 2 . After 7 daily [ 14 C] oral doses, terminal phase radioactive tissue residues were higher from the acetamide radiolabel, relative to the oxazolidinone radiolabel, and were primarily not drug-related. In the definitive tissue distribution study, low concentrations of drug-related radioactivity in skin and thyroid were observed. We conclude that although small amounts of radiolabel instability do not significantly affect single dose tissue radioactivity C max and area under the curve (AUC), artifacts arising from radiolabel instability can prolong the apparent terminal phase half life and complicate study data interpretation. When possible, it is always preferable to use a completely stable radiolabel site. (author)

  16. Immunotherapy with GD2 specific monoclonal antibodies

    International Nuclear Information System (INIS)

    Cheung, N.K.V.; Medof, E.M.; Munn, D.

    1988-01-01

    Targeted immunotherapy focuses anti-tumor activity of antibodies and effector cells, which are actively developed by the host or adoptively transferred, onto tumor cells and into tumor sites. Such tumor selective therapy can be more specific and efficient. The value of such an approach is evident in the classical interaction of antibodies. This paper reports that the ganglioside G D2 is an ideal antigen for specific tumor targeting because of its relative lack of heterogeneity among human neuroblastoma, its high density on tumor cells, its lack of antigen modulation upon binding to antibody, and its restricted distribution in normal tissues

  17. 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.

  18. Advances in infectious foci imaging using 99mTc radiolabelled antibiotics

    International Nuclear Information System (INIS)

    Seyedeh Fatemeh Mirshojaei

    2015-01-01

    Conventional methods of infection diagnosis, relying on experimental tests and culture of organisms from infected foci have continued to developing new technologies and automation. Nuclear medicine is a reliable diagnostic technique capable to detect infectious foci in human disease. A wide range of radiolabeled agents have been evaluated for demonstrating their ability to distinguish microbial infectious lesions. New researches continue to be made on the use of radiolabeled antibiotics which as well as being highly specific in the diagnosis of infection would be useful in monitoring of disease treatment. Here, the new approaches of infection scintigraphic imaging by radiolabeled antibiotics are thoroughly discussed in order to assess and compare their diagnostic value as targeting imaging radiopharmaceuticals. (author)

  19. Microreactor and method for preparing a radiolabeled complex or a biomolecule conjugate

    Energy Technology Data Exchange (ETDEWEB)

    Reichert, David E; Kenis, Paul J. A.; Wheeler, Tobias D; Desai, Amit V; Zeng, Dexing; Onal, Birce C

    2015-03-17

    A microreactor for preparing a radiolabeled complex or a biomolecule conjugate comprises a microchannel for fluid flow, where the microchannel comprises a mixing portion comprising one or more passive mixing elements, and a reservoir for incubating a mixed fluid. The reservoir is in fluid communication with the microchannel and is disposed downstream of the mixing portion. A method of preparing a radiolabeled complex includes flowing a radiometal solution comprising a metallic radionuclide through a downstream mixing portion of a microchannel, where the downstream mixing portion includes one or more passive mixing elements, and flowing a ligand solution comprising a bifunctional chelator through the downstream mixing portion. The ligand solution and the radiometal solution are passively mixed while in the downstream mixing portion to initiate a chelation reaction between the metallic radionuclide and the bifunctional chelator. The chelation reaction is completed to form a radiolabeled complex.

  20. Current status and future perspectives of in vivo small animal imaging using radiolabeled nanoparticles

    International Nuclear Information System (INIS)

    Loudos, George; Kagadis, George C.; Psimadas, Dimitris

    2011-01-01

    Small animal molecular imaging is a rapidly expanding efficient tool to study biological processes non-invasively. The use of radiolabeled tracers provides non-destructive, imaging information, allowing time related phenomena to be repeatedly studied in a single animal. In the last decade there has been an enormous progress in related technologies and a number of dedicated imaging systems overcome the limitations that the size of small animal possesses. On the other hand, nanoparticles (NPs) gain increased interest, due to their unique properties, which make them perfect candidates for biological applications. Over the past 5 years the two fields seem to cross more and more often; radiolabeled NPs have been assessed in numerous pre-clinical studies that range from oncology, till HIV treatment. In this article the current status in the tools, applications and trends of radiolabeled NPs reviewed.

  1. Investigation of bacterial adherence to a non-precious alloy with radiolabeling method

    International Nuclear Information System (INIS)

    Sonugelen, M.; Iyiyapici Destan, U.; Oeztuerk, B.; Yurt Lambrecht, F.

    2006-01-01

    The objective of this study was to investigate the bacterial adherence to a non-precious alloy with radiolabeling method. S. mutans, E. coliand C. albicanswere labeled with 99m Tc by using stannous chloride and their radiolabeling yields were calculated. After the labeling procedure, metal disks (3 mm x 10 mm) were treated with microorganisms. The amount of labeled microorganisms adhered on metal surfaces was determined by activity measurements. The labeling yields for S. mutans, E. coliand C. albicanswere 69.95 ± 7.58%, 78.84 ± 0.44% and 79.71 ± 10.17%, respectively. The mean values for adherence for S. mutans, E. coliand C. albicans on metal samples were 7.02 ± 2.18%, 0.96 ± 0.49% and 8.80 ± 8.24%, respectively. The radiolabeling method could be considered as safe and precise for determining the adherence of microorganisms. (author)

  2. Effector Regulatory T Cells Reflect the Equilibrium between Antitumor Immunity and Autoimmunity in Adult T-cell Leukemia.

    Science.gov (United States)

    Ureshino, Hiroshi; Shindo, Takero; Nishikawa, Hiroyoshi; Watanabe, Nobukazu; Watanabe, Eri; Satoh, Natsuko; Kitaura, Kazutaka; Kitamura, Hiroaki; Doi, Kazuko; Nagase, Kotaro; Kimura, Hiromi; Samukawa, Makoto; Kusunoki, Susumu; Miyahara, Masaharu; Shin-I, Tadasu; Suzuki, Ryuji; Sakaguchi, Shimon; Kimura, Shinya

    2016-08-01

    The regulatory T cells (Treg) with the most potent immunosuppressive activity are the effector Tregs (eTreg) with a CD45RA(-)Foxp3(++)CCR4(+) phenotype. Adult T-cell leukemia (ATL) cells often share the Treg phenotype and also express CCR4. Although mogamulizumab, a monoclonal antibody to CCR4, shows marked antitumor effects against ATL and peripheral T-cell lymphoma, concerns have been raised that it may induce severe autoimmune immunopathology by depleting eTregs. Here, we present case reports for two patients with ATL who responded to mogamulizumab but developed a severe skin rash and autoimmune brainstem encephalitis. Deep sequencing of the T-cell receptor revealed that ATL cells and naturally occurring Tregs within the cell population with a Treg phenotype can be clearly distinguished according to CADM1 expression. The onset of skin rash and brainstem encephalitis was coincident with eTreg depletion from the peripheral blood, whereas ATL relapses were coincident with eTreg recovery. These results imply that eTreg numbers in the peripheral blood sensitively reflect the equilibrium between antitumor immunity and autoimmunity, and that mogamulizumab might suppress ATL until the eTreg population recovers. Close monitoring of eTreg numbers is crucial if we are to provide immunomodulatory treatments that target malignancy without severe adverse events. Cancer Immunol Res; 4(8); 644-9. ©2016 AACR. ©2016 American Association for Cancer Research.

  3. In vitro metabolism of radiolabeled carbohydrates by protective cecal anaerobic bacteria.

    Science.gov (United States)

    Hume, M E; Beier, R C; Hinton, A; Scanlan, C M; Corrier, D E; Peterson, D V; DeLoach, J R

    1993-12-01

    Cecal anaerobic bacteria from adult broilers were cultured in media containing .25% glucose or .25% lactose. Media also contained either [14C]-labeled lactose, glucose, galactose, or lactic acid as metabolic tracers. Cultures were analyzed at 4, 8, and 12 h for pH, radiolabeled and unlabeled volatile fatty acids, and lactic acid. The pH values of cultures containing .25% lactose were significantly (P galactose, lactose > glucose. The volatile fatty acids in which radiolabel was most concentrated were acetic acid, propionic acid, or butyric acid.

  4. Progresses in optimization strategy for radiolabeled molecular probes targeting integrin αvβ3

    International Nuclear Information System (INIS)

    Chen Haojun; Wu Hua

    2012-01-01

    Tumor angiogenesis is critical in the growth, invasion and metastasis of malignant tumors. The integrins, which express on many types of tumor cells and activated vascular endothelial cells, play an important role in regulation of the tumor angiogenesis. RGD peptide, which contains Arg-Gly-Asp sequence, binds specifically to integrin α v β 3 . Therefore, the radiolabeled RGD peptides may have broad application prospects in radionuclide imaging and therapy. Major research interests include the selection of radionuclides, modification and improvement of RGD structures. In this article, we give a review on research progresses in optimization strategy for radiolabeled molecular probes targeting integrin α v β 3 . (authors)

  5. Method for radio imaging the myocardium of mammals using radio-labelled lipophil cations

    International Nuclear Information System (INIS)

    1984-01-01

    The invention relates to a method for the radio imaging of myocardia of mammals by concentrating a radiolabelled cation in myocardial tissue and by producing a radiograph using imaging techniques. According to the invention, it is found that a group of substances shows a preference to myocardial tissues upon intravenous injection in mammals. The characteristic of the invention is that radiolabelled quaternary ammonium, quaternary phosphorous or quaternary arsenic compounds with at least two aryl groups are intravenously injected. These substances provide a sufficiently high radioactivity giving an approved diagnostic image of the myocardium. (G.J.P.)

  6. Antibody complementarity-determining regions (CDRs can display differential antimicrobial, antiviral and antitumor activities.

    Directory of Open Access Journals (Sweden)

    Luciano Polonelli

    Full Text Available BACKGROUND: Complementarity-determining regions (CDRs are immunoglobulin (Ig hypervariable domains that determine specific antibody (Ab binding. We have shown that synthetic CDR-related peptides and many decapeptides spanning the variable region of a recombinant yeast killer toxin-like antiidiotypic Ab are candidacidal in vitro. An alanine-substituted decapeptide from the variable region of this Ab displayed increased cytotoxicity in vitro and/or therapeutic effects in vivo against various bacteria, fungi, protozoa and viruses. The possibility that isolated CDRs, represented by short synthetic peptides, may display antimicrobial, antiviral and antitumor activities irrespective of Ab specificity for a given antigen is addressed here. METHODOLOGY/PRINCIPAL FINDINGS: CDR-based synthetic peptides of murine and human monoclonal Abs directed to: a a protein epitope of Candida albicans cell wall stress mannoprotein; b a synthetic peptide containing well-characterized B-cell and T-cell epitopes; c a carbohydrate blood group A substance, showed differential inhibitory activities in vitro, ex vivo and/or in vivo against C. albicans, HIV-1 and B16F10-Nex2 melanoma cells, conceivably involving different mechanisms of action. Antitumor activities involved peptide-induced caspase-dependent apoptosis. Engineered peptides, obtained by alanine substitution of Ig CDR sequences, and used as surrogates of natural point mutations, showed further differential increased/unaltered/decreased antimicrobial, antiviral and/or antitumor activities. The inhibitory effects observed were largely independent of the specificity of the native Ab and involved chiefly germline encoded CDR1 and CDR2 of light and heavy chains. CONCLUSIONS/SIGNIFICANCE: The high frequency of bioactive peptides based on CDRs suggests that Ig molecules are sources of an unlimited number of sequences potentially active against infectious agents and tumor cells. The easy production and low cost of small

  7. 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.

  8. (99m)Tc-aprotinin - optimisation and validation of radiolabelling kits for routine preparation for diagnostic imaging of amyloidosis

    DEFF Research Database (Denmark)

    Denholt, Charlotte; Gillings, Nic

    2016-01-01

    Technetium-99m aprotinin was prepared from an optimised radiolabelling kit formulation containing aprotinin, alkaline buffer and stannous chloride (reducing agent) and radiolabelled using (99m) Tc-pertechnetate. The labelling was achieved within 25 min, with radiochemical purities of >98%....

  9. EFFICACY EVALUATION OF A MONOCLONAL ANTIBODY AGAINST THE EPIDERMAL GROWTH FACTORS RECEPTOR IN THE MODEL OF SUBCUTANEOUS XENOGRAFT IN IMMUNODEFICIENT MICE

    Directory of Open Access Journals (Sweden)

    Ya. Yu. Ustyugov

    2015-01-01

    Full Text Available This article presents the results of the comparative antitumor efficacy study of two test articles of therapeutic humanized monoclonal antibodies against epidermal growth factor receptor (EGFR manufactured by Russian biopharmaceutical company CJSC “Biocad” and the commercial drug “Erbitux®” (Merck, Germany in subcutaneous xenografts model using human epidermoid carcinoma A431NS cell line. EGFR overexpression in epithelial tumor cells is a commonly known fact that determines use of this receptor as a target for therapeutic monoclonal antibodies. The basic mechanism of action of such drugs is blocking of epithelial cells proliferation through competitive binding to EGFR. Evaluation of tumor growth dynamics in immunodeficient (Nu/Nu mice was performed during in vivo experiment using two parameters: tumor growth index and tumor growth inhibition (TGI, %. The results received with used study design show that antitumor effects of the test articles manufactured by CJSC “Biocad” and the commercial comparator drug “Erbitux®” estimated by values of TGI and tumor growth index are comparable.

  10. 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.

  11. 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.

  12. 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 ...

  13. 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.

  14. 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

  15. Assessment of in vitro antitumoral and antimicrobial activities of ...

    African Journals Online (AJOL)

    Assessment of in vitro antitumoral and antimicrobial activities of marine algae harvested from the eastern Mediterranean sea. ... African Journal of Biotechnology ... algal extracts obtained from the marine algae Scytosiphon lomentaria, Padina pavonica, Cystoseira mediterranea (Phaeophyceae), Hypnea musciformis and ...

  16. Effects of Androgen Ablation on Anti-Tumor Immunity

    National Research Council Canada - National Science Library

    Kast, Martin

    2004-01-01

    .... This AA induced autoimmune-like response exerts limited anti-tumor activity in a murine prostate cancer model, but could be synergistic with CTLA-4 blockade that promotes the development of autoreactive T cell...

  17. Gut microbiome can control antitumor immune function in liver

    Science.gov (United States)

    An NCI study in mice that found a connection between gut bacteria and antitumor immune responses in the liver has implications for understanding mechanisms that lead to liver cancer and for potential treatments. The study was published in Science.

  18. 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...

  19. Enhanced specificity in immunoscreening of expression cDNA clones using radiolabeled antigen overlay

    International Nuclear Information System (INIS)

    Chao, S.; Chao, L.; Chao, J.

    1989-01-01

    A highly sensitive and specific method has been developed for immunoscreening clones from an expression cDNA library. The procedures utilize a radiolabeled antigen detection method described originally for the immunoblotting of plasma proteins. Screening of rat alpha 1-antitrypsin clones was used. Comparison between Western blots of alpha 1-antitrypsin using both labeled antigen and protein A detection methods showed that the former yielded lower background and greater sensitivity than the latter. Further, this technique was shown to have a lower detection limit of less than 20 ng through Western blot analysis of varying concentrations of alpha 1-antitrypsin. The procedures are based on the expression of the protein by cDNA clones containing the DNA inserts in the correct reading frame. Following the transfer of phage proteins to nitrocellulose membranes, the bivalent antibodies bind monovalently to both nitrocellulose-bound-antigen in the phage lysates and radiolabeled antigen. The radiolabeled antigen overlay method is superior to the protein A detection method in sensitivity, specificity and reproducibility. This improved method can be applied in general for screening expression cDNA libraries, provided that the specific antiserum and radiolabeled antigen are available

  20. Partition of radiolabeled amino acids in detached wheat heads in culture

    International Nuclear Information System (INIS)

    Inwood, W.; Bernardin, J.

    1990-01-01

    The concentration of a particular amino acid supplied to a detached wheat head affected the ultimate distribution of that amino acid among the tissues of the head. Detached wheat heads (Triticum aestivum L. cv Cheyenne) were supplied with a pulse of [ 3 H]leucine in the culture medium and were chased with medium that contained glutamine as the sole nitrogen source. When the amount of radiolabel was held constant, an increasing concentration of unlabeled leucine in the pulse medium led to an increased partition of the radiolabel into the grain tissues of the head. When the concentration of unlabeled leucine was increased from zero to radiolabeled leucine was partitioned to endosperm tissue and twice as much to seedcoat tissues. An effect of amino acid concentration on radiolabel partition was also found for methionine and proline, but the effect was not as dramatic. These results suggest the existence of an amino acid transport system between the transpiration stream of the wheat head and the grain that exhibits cooperative kinetics or amino acid activation

  1. SPECT/CT imaging of radiolabeled cubosomes and hexosomes for potential theranostic applications

    DEFF Research Database (Denmark)

    Nilsson, Christa; Barrios-Lopez, Brianda; Kallinen, Annukka

    2013-01-01

    We have developed a highly efficient method for the radiolabeling of phytantriol (PHYT)/oleic acid (OA)-based hexosomes based on the surface chelation of technetium-99m ((99m)Tc) to preformed hexosomes using the polyamine 1, 12-diamino-3, 6, 9-triazododecane (SpmTrien) as chelating agent. We also...

  2. Long-circulating liposomes radiolabeled with [18F]fluorodipalmitin ([18F]FDP)

    International Nuclear Information System (INIS)

    Marik, Jan; Tartis, Michaelann S.; Zhang, Hua; Fung, Jennifer Y.; Kheirolomoom, Azadeh; Sutcliffe, Julie L.; Ferrara, Katherine W.

    2007-01-01

    Synthesis of a radiolabeled diglyceride, 3-[ 18 F]fluoro-1,2-dipalmitoylglycerol [[ 18 F]fluorodipalmitin ([ 18 F]FDP)], and its potential as a reagent for radiolabeling long-circulating liposomes were investigated. The incorporation of 18 F into the lipid molecule was accomplished by nucleophilic substitution of the p-toluenesulfonyl moiety with a decay-corrected yield of 43±10% (n=12). Radiolabeled, long-circulating polyethylene-glycol-coated liposomes were prepared using a mixture of 1,2-dipalmitoyl-sn-glycero-3-phosphocholine, cholesterol, 1,2-distearoyl-sn-glycero-3-phosphoethanolamine-N- [methoxy(polyethyleneglycol)-2000] ammonium salt (61:30:9) and [ 18 F]FDP with a decay-corrected yield of 70±8% (n=4). PET imaging and biodistribution studies were performed with free [ 18 F]FDP and liposome-incorporated [ 18 F]FDP. Freely injected [ 18 F]FDP had the highest uptake in the liver, spleen and lungs. Liposomal [ 18 F]FDP remained in blood circulation at near-constant levels for at least 90 min, with a peak concentration near 2.5%ID/cc. Since [ 18 F]FDP was incorporated into the phospholipid bilayer, it could potentially be used for radiolabeling a variety of lipid-based drug carriers

  3. Radiolabeling of VEGF(165) with Tc-99m to evaluate VEGFR expression in tumor angiogenesis

    NARCIS (Netherlands)

    Galli, Filippo; Artico, Marco; Taurone, Samanta; Manni, Isabella; Bianchi, Enrica; Piaggio, Giulia; Weintraub, Bruce D.; Szkudlinski, Mariusz W.; Agostinelli, Enzo; Dierckx, Rudi A. J. O.; Signore, Alberto

    Angiogenesis is the main process responsible for tumor growth and metastatization. The principal effector of such mechanism is the vascular endothelial growth factor (VEGF) secreted by cancer cells and other components of tumor microenvironment. Radiolabeled VEGF analogues may provide a useful tool

  4. Lymphoma: current status of clinical and preclinical imaging with radiolabeled antibodies

    Energy Technology Data Exchange (ETDEWEB)

    England, Christopher G. [University of Wisconsin School of Medicine and Public Health, Department of Medical Physics, Madison, WI (United States); Rui, Lixin [University of Wisconsin School of Medicine and Public Health, Department of Medicine, Madison, WI (United States); University of Wisconsin School of Medicine and Public Health, Carbone Cancer Center, Madison, WI (United States); Cai, Weibo [University of Wisconsin School of Medicine and Public Health, Department of Medical Physics, Madison, WI (United States); University of Wisconsin School of Medicine and Public Health, Carbone Cancer Center, Madison, WI (United States); University of Wisconsin School of Medicine and Public Health, Department of Radiology, Madison, WI (United States)

    2017-03-15

    Lymphoma is a complex disease that arises from cells of the immune system with an intricate pathology. While lymphoma may be classified as Hodgkin or non-Hodgkin, each type of tumor is genetically and phenotypically different and highly invasive tissue biopsies are the only method to investigate these differences. Noninvasive imaging strategies, such as immunoPET, can provide a vital insight into disease staging, monitoring treatment response in patients, and dose planning in radioimmunotherapy. ImmunoPET imaging with radiolabeled antibody-based tracers may also assist physicians in optimizing treatment strategies and enhancing patient stratification. Currently, there are two common biomarkers for molecular imaging of lymphoma, CD20 and CD30, both of which have been considered for investigation in preclinical imaging studies. In this review, we examine the current status of both preclinical and clinical imaging of lymphoma using radiolabeled antibodies. Additionally, we briefly investigate the role of radiolabeled antibodies in lymphoma therapy. As radiolabeled antibodies play critical roles in both imaging and therapy of lymphoma, the development of novel antibodies and the discovery of new biomarkers may greatly affect lymphoma imaging and therapy in the future. (orig.)

  5. Species specific uptake of radio-labelled phytodetritus by benthic meiofauna from the Baltic Sea

    NARCIS (Netherlands)

    Ólafsson, E.; Modig, H.; Van de Bund, W.J.

    1999-01-01

    The diatom Sheletonema costatum is one of the dominant phytoplankton species during spring in the northern Baltic Sea. We followed the uptake of radio-labelled S, costatum by all major meiofauna species in a laboratory experiment. The uptake of labelled diatom carbon varied greatly among major

  6. Progress of radiolabelled bombesin in diagnosis and treatment of prostate cancer

    International Nuclear Information System (INIS)

    Xing Yan; Zhao Jihua

    2010-01-01

    Studies show that high expression of bombesin exist in the face of many kind of tumors such as prostate cancer, so bombesin and its receptor can be used as target in radionuclide receptor imaging and targeted therapy of tumor, and become the focus of prostate cancer research. This article reviews the progress of radiolabelled bombesin in prostate cancer imaging and therapy. (authors)

  7. Studies towards the synthesis of radiolabeled R106-1(LY295337)

    International Nuclear Information System (INIS)

    Rodriguez, M.J.; Zweifel, M.J.

    1996-01-01

    A unique semisynthetic pathway has been used as a route to acquire radiolabeled material of a complex natural product, R106. The retro-aldol reaction of R106-1 gave a key intermediate R106-sarcosine that was used in a subsequent aldol reaction to incorporate acetone--[2- 14 C]. (author)

  8. Lymphoma: current status of clinical and preclinical imaging with radiolabeled antibodies

    International Nuclear Information System (INIS)

    England, Christopher G.; Rui, Lixin; Cai, Weibo

    2017-01-01

    Lymphoma is a complex disease that arises from cells of the immune system with an intricate pathology. While lymphoma may be classified as Hodgkin or non-Hodgkin, each type of tumor is genetically and phenotypically different and highly invasive tissue biopsies are the only method to investigate these differences. Noninvasive imaging strategies, such as immunoPET, can provide a vital insight into disease staging, monitoring treatment response in patients, and dose planning in radioimmunotherapy. ImmunoPET imaging with radiolabeled antibody-based tracers may also assist physicians in optimizing treatment strategies and enhancing patient stratification. Currently, there are two common biomarkers for molecular imaging of lymphoma, CD20 and CD30, both of which have been considered for investigation in preclinical imaging studies. In this review, we examine the current status of both preclinical and clinical imaging of lymphoma using radiolabeled antibodies. Additionally, we briefly investigate the role of radiolabeled antibodies in lymphoma therapy. As radiolabeled antibodies play critical roles in both imaging and therapy of lymphoma, the development of novel antibodies and the discovery of new biomarkers may greatly affect lymphoma imaging and therapy in the future. (orig.)

  9. Antitumor effects and mechanisms of Ganoderma extracts and spores oil

    OpenAIRE

    Chen, Chun; Li, Peng; Li, Ye; Yao, Guan; Xu, Jian-Hua

    2016-01-01

    Ganoderma lucidum is a popular herbal medicine used in China to promote health. Modern studies have disclosed that the active ingredients of Ganoderma can exhibit several effects, including antitumor effects and immunomodulation. The present study evaluated the antitumor effects of self-prepared Ganoderma extracts and spores oil, and investigated the possible underlying mechanisms by observing the effects of the extracts and oil on topoisomerases and the cell cycle. The results showed that Ga...

  10. 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

  11. Site-specifically {sup 89}Zr-labeled monoclonal antibodies for ImmunoPET

    Energy Technology Data Exchange (ETDEWEB)

    Tinianow, Jeff N.; Gill, Herman S.; Ogasawara, Annie; Flores, Judith E.; Vanderbilt, Alexander N.; Luis, Elizabeth; Vandlen, Richard; Darwish, Martine; Junutula, Jagath R.; Williams, Simon-P. [Genentech Research and Early Development, Genentech Inc., South San Francisco, CA 94080 (United States); Marik, Jan [Genentech Research and Early Development, Genentech Inc., South San Francisco, CA 94080 (United States)], E-mail: marik.jan@gene.com

    2010-04-15

    Three thiol reactive reagents were developed for the chemoselective conjugation of desferrioxamine (Df) to a monoclonal antibody via engineered cysteine residues (thio-trastuzumab). The in vitro stability and in vivo imaging properties of site-specifically radiolabeled {sup 89}Zr-Df-thio-trastuzumab conjugates were investigated. Methods: The amino group of desferrioxamine B was acylated by bromoacetyl bromide, N-hydroxysuccinimidyl iodoacetate, or N-hydroxysuccinimidyl 4-[N-maleimidomethyl]cyclohexane-1-carboxylate to obtain thiol reactive reagents bromoacetyl-desferrioxamine (Df-Bac), iodoacetyl-desferrioxamine (Df-Iac) and maleimidocyclohexyl-desferrioxamine (Df-Chx-Mal), respectively. Df-Bac and Df-Iac alkylated the free thiol groups of thio-trastuzumab by nucleophilic substitution forming Df-Ac-thio-trastuzumab, while the maleimide reagent Df-Chx-Mal reacted via Michael addition to provide Df-Chx-Mal-thio-trastuzumab. The conjugates were radiolabeled with {sup 89}Zr and evaluated for serum stability, and their positron emission tomography (PET) imaging properties were investigated in a BT474M1 (HER2-positive) breast tumor mouse model. Results: The chemoselective reagents were obtained in 14% (Df-Bac), 53% (Df-Iac) and 45% (Df-Chx-Mal) yields. Site-specific conjugation of Df-Chx-Mal to thio-trastuzumab was complete within 1 h at pH 7.5, while Df-Iac and Df-Bac respectively required 2 and 5 h at pH 9. Each Df modified thio-trastuzumab was chelated with {sup 89}Zr in yields exceeding 75%. {sup 89}Zr-Df-Ac-thio-trastuzumab and {sup 89}Zr-Df-Chx-Mal-thio-trastuzumab were stable in mouse serum and exhibited comparable PET imaging capabilities in a BT474M1 (HER2-positive) breast cancer model reaching 20-25 %ID/g of tumor uptake and a tumor to blood ratio of 6.1-7.1. Conclusions: The new reagents demonstrated good reactivity with engineered thiol groups of trastuzumab and very good chelation properties with {sup 89}Zr. The site-specifically {sup 89}Zr-labeled thio

  12. Synthesis of fluorine-18 radio-labeled serum albumins for PET blood pool imaging

    International Nuclear Information System (INIS)

    Basuli, Falguni; Li, Changhui; Xu, Biying; Williams, Mark; Wong, Karen; Coble, Vincent L.; Vasalatiy, Olga; Seidel, Jurgen; Green, Michael V.; Griffiths, Gary L.; Choyke, Peter L.; Jagoda, Elaine M.

    2015-01-01

    We sought to develop a practical, reproducible and clinically translatable method of radiolabeling serum albumins with fluorine-18 for use as a PET blood pool imaging agent in animals and man. Fluorine-18 radiolabeled fluoronicotinic acid-2,3,5,6-tetrafluorophenyl ester, [ 18 F]F-Py-TFP was prepared first by the reaction of its quaternary ammonium triflate precursor with [ 18 F]tetrabutylammonium fluoride ([ 18 F]TBAF) according to a previously published method for peptides, with minor modifications. The incubation of [ 18 F]F-Py-TFP with rat serum albumin (RSA) in phosphate buffer (pH 9) for 15 min at 37–40 °C produced fluorine-18-radiolabeled RSA and the product was purified using a mini-PD MiniTrap G-25 column. The overall radiochemical yield of the reaction was 18–35% (n = 30, uncorrected) in a 90-min synthesis. This procedure, repeated with human serum albumin (HSA), yielded similar results. Fluorine-18-radiolabeled RSA demonstrated prolonged blood retention (biological half-life of 4.8 hours) in healthy awake rats. The distribution of major organ radioactivity remained relatively unchanged during the 4 hour observation periods either by direct tissue counting or by dynamic PET whole-body imaging except for a gradual accumulation of labeled metabolic products in the bladder. This manual method for synthesizing radiolabeled serum albumins uses fluorine-18, a widely available PET radionuclide, and natural protein available in both pure and recombinant forms which could be scaled up for widespread clinical applications. These preclinical biodistribution and PET imaging results indicate that [ 18 F]RSA is an effective blood pool imaging agent in rats and might, as [ 18 F]HSA, prove similarly useful as a clinical imaging agent

  13. In vitro and in vivo analysis of radiolabeled clindamycin hydrogel gel by radioscintigraphic techniques

    International Nuclear Information System (INIS)

    Kumar, N.; Datta, M.; Chopra, M.K.; Soni, N.L.; Mittal, G.; Singh, T.; Bhatnagar, A.; Bhawna

    2010-01-01

    Full text: Acne is one of the common dermatological problems caused by microorganism Acne vulgaris, therefore being used commonly in the treatment of acne. Clindamycin is the 7- deoxy, 7- chloro congener of the lincomycin, a macrolide antibiotic derived from Streptomyces lincolnensis. This study was performed for in-vitro and in-vivo estimation of radiolabeled clindamycin hydrogel using radioscintigraphic techniques for transdermal permeation. Clindamycin was supplied as a gift sample by Glenmark Research Laboratory (Mumbai, India) and other chemicals and reagents used were of analytical grade and were purchased from Merck Chemicals (India). Clindamycin was radiolabeled with 99m Tc-pertechnetate using stannous chloride as a reducing agent. Radiolabeled clindamycin was characterized for its stability at room temperature and in physiological conditions (serum). Clindamycin hydrogel was prepared by dispersion of radiolabeled clindamycin in carbopol 980 containing polaxomer as surfactant and methyl paraben as preservative solution. The prepared hydrogel was analysed for in vitro analysis via franz diffusion cell and in vivo studies were performed in balb-C mice for biodistribution and skin permeation and were analysed by radiometry. The results obtained showed labeling efficiency of clindamycin was more than 90%, and that was consistent and the radiolabeled drug was stable upto 24 hrs in serum. In vitro release studies showed an increased release rate till four hours and it's become plateaus after 4 hours. In vivo biodistribution studies were showed 99m Tc clindamycin hydrogel remains stable and follow predominantly hepatic excretion. Biodistribution pattern suggests late redistribution from a storage sight, probably, body fats

  14. Synthesis of fluorine-18 radio-labeled serum albumins for PET blood pool imaging.

    Science.gov (United States)

    Basuli, Falguni; Li, Changhui; Xu, Biying; Williams, Mark; Wong, Karen; Coble, Vincent L; Vasalatiy, Olga; Seidel, Jurgen; Green, Michael V; Griffiths, Gary L; Choyke, Peter L; Jagoda, Elaine M

    2015-03-01

    We sought to develop a practical, reproducible and clinically translatable method of radiolabeling serum albumins with fluorine-18 for use as a PET blood pool imaging agent in animals and man. Fluorine-18 radiolabeled fluoronicotinic acid-2,3,5,6-tetrafluorophenyl ester, [(18)F]F-Py-TFP was prepared first by the reaction of its quaternary ammonium triflate precursor with [(18)F]tetrabutylammonium fluoride ([(18)F]TBAF) according to a previously published method for peptides, with minor modifications. The incubation of [(18)F]F-Py-TFP with rat serum albumin (RSA) in phosphate buffer (pH9) for 15 min at 37-40 °C produced fluorine-18-radiolabeled RSA and the product was purified using a mini-PD MiniTrap G-25 column. The overall radiochemical yield of the reaction was 18-35% (n=30, uncorrected) in a 90-min synthesis. This procedure, repeated with human serum albumin (HSA), yielded similar results. Fluorine-18-radiolabeled RSA demonstrated prolonged blood retention (biological half-life of 4.8 hours) in healthy awake rats. The distribution of major organ radioactivity remained relatively unchanged during the 4 hour observation periods either by direct tissue counting or by dynamic PET whole-body imaging except for a gradual accumulation of labeled metabolic products in the bladder. This manual method for synthesizing radiolabeled serum albumins uses fluorine-18, a widely available PET radionuclide, and natural protein available in both pure and recombinant forms which could be scaled up for widespread clinical applications. These preclinical biodistribution and PET imaging results indicate that [(18)F]RSA is an effective blood pool imaging agent in rats and might, as [(18)F]HSA, prove similarly useful as a clinical imaging agent. Published by Elsevier Inc.

  15. Initial clinical evaluation of radiolabeled MX-DTPA humanized BrE-3 antibody in patients with advanced breast cancer.

    Science.gov (United States)

    Kramer, E L; Liebes, L; Wasserheit, C; Noz, M E; Blank, E W; Zabalegui, A; Melamed, J; Furmanski, P; Peterson, J A; Ceriani, R L

    1998-07-01

    To evaluate radiometal-labeled humanized BrE-3 (huBrE-3) monoclonal antibody as a radioimmunolocalization and therapeutic agent in breast cancer patients, tumor localization, pharmacokinetics, radiation dosimetry, and immunogenicity of (111)In-labeled combined 1-p-isothiocyanatobenzyl 3-methyl- and 1-p-isothiocyanatobenzyl 4-methyldiethylenetriamine pentaacetic acid (MX-DTPA) huBrE-3 were studied. Seven women with BrE-3 antigen-positive, metastatic breast carcinoma underwent (111)In huBrE-3 infusion (5 mCi; 50 mg), followed by serial gamma camera imaging and plasma sampling. Region of interest analysis of images was used to make radiation absorbed dose estimates for (111)In huBrE-3. Data were extrapolated to 90Y huBrE-3. Human anti-human antibody (HAHA) response was measured in serum samples obtained up to 3 months after infusion. Patients tolerated infusions well. Seventy-six percent of 105 known sites of disease were identified on planar and single-photon emission computed tomography scans. For six of seven patients, a biexponential model fit the plasma time-activity curve best with an average T1/2alpha=10.6+/-8.5 (SD) h and average T1/2beta=114.2+/-39.2 h. Radiation absorbed dose estimates for (111)In huBrE-3 for whole body averaged 0.53+/-.08 rads/mCi. Dose estimates for 90Y huBrE-3 for marrow averaged 8.4+/-11.9 rads/mCi, and for tumors, 70+/-31.5 rads/mCi. Liver radioactivity uptake averaged 19.7+/-8.8% injected dose at 24 h after infusion, translating into an average radiation absorbed dose 21.1+/-12 rads/90Y mCi administered. Only one of seven patients demonstrated a low level of HAHA response. Although the plasma half-lives are longer and marrow dose higher for radiolabeled huBrE-3 compared with the murine construct, the excellent tumor localization, good tumor dosimetry, and low immunogenicity support the use of 90Y-huBrE-3 antibody for radioimmunotherapy of breast cancer.

  16. Advanced nanocarriers for an antitumor peptide

    Energy Technology Data Exchange (ETDEWEB)

    Pippa, Natassa [National and Kapodistrian University of Athens, Department of Pharmaceutical Technology, Faculty of Pharmacy (Greece); Pispas, Stergios [National Hellenic Research Foundation, Theoretical and Physical Chemistry Institute (Greece); Demetzos, Costas, E-mail: demetzos@pharm.uoa.gr [National and Kapodistrian University of Athens, Department of Pharmaceutical Technology, Faculty of Pharmacy (Greece); Sivolapenko, Gregory [University of Patras, Laboratory of Pharmacokinetics, Department of Pharmacy (Greece)

    2013-11-15

    In this work, tigapotide (PCK3145) was incorporated into novel nanocarriers based on polymeric, lipidic, and dendrimeric components, in order to maximize the advantages of the drug delivery process and possibly its biological properties. PCK3145 was incorporated into lipidic nanocarriers composed of Egg phosphatidylcholine (EggPC) and dipalmytoylphosphatidylcholine (DPPC) (EggPC:PCK3145 and DPPC:PCK3145, 9:0.2 molar ratio), into cationic liposomes composed of EggPC:SA:PCK3145 and DPPC:SA:PCK3145 (9:1:0.2 molar ratio) into complexes with the block polyelectrolyte (quaternized poly[3,5-bis(dimethylaminomethylene)hydroxystyrene]-b-poly(ethylene oxide) (QNPHOSEO) and finally into dendrimeric structures (i.e., PAMAM G4). Light scattering techniques are used in order to examine the size, the size distribution and the Z-potential of the nanocarriers in aqueous and biological media. Fluorescence spectroscopy was utilized in an attempt to extract information on the internal nanostructure and microenvironment of polyelectrolyte/PCK3145 aggregates. Therefore, these studies could be a rational roadmap for producing various effective nanocarriers in order to ameliorate the pharmacokinetic behavior and safety issues of antitumor and anticancer biomolecules.

  17. Antitumor Effect of Burchellin Derivatives Against Neuroblastoma.

    Science.gov (United States)

    Kurita, Masahiro; Takada, Tomomi; Wakabayashi, Noriko; Asami, Satoru; Ono, Shinichi; Uchiyama, Taketo; Suzuki, Takashi

    2018-02-01

    Neuroblastoma is one of the most commonly encountered malignant solid tumors in the pediatric age group. We examined the antitumor effects of five burchellin derivatives against human neuroblastoma cell lines. We evaluated cytotoxicity by the MTT assay for four human neuroblastoma and two normal cell lines. We also performed analysis of the apoptotic induction effect by flow cytometry, and examined the expression levels of apoptosis- and cell growth-related proteins by western blot analysis. We found that one of the burchellin derivatives (compound 4 ) exerted cytotoxicity against the neuroblastoma cell lines. Compound 4 induced caspase-dependent apoptosis via a mitochondrial pathway. The apoptosis mechanisms induced by compound 4 involved caspase-3, -7 and -9 activation and poly (ADP-ribose) polymerase cleavage. In addition, compound 4 induced cell death through inhibition of the cell growth pathway (via extracellular signal-regulated kinase 1 and 2, AKT8 virus oncogene cellular homolog, and signal transducer and activator of transcription 3). Compound 4 exerted cellular cytotoxicity against neuroblastoma cells via induction of caspase-dependent apoptosis, and may offer promise for further development as a useful drug for the treatment of advanced neuroblastoma. Copyright© 2018, International Institute of Anticancer Research (Dr. George J. Delinasios), All rights reserved.

  18. Advanced nanocarriers for an antitumor peptide

    International Nuclear Information System (INIS)

    Pippa, Natassa; Pispas, Stergios; Demetzos, Costas; Sivolapenko, Gregory

    2013-01-01

    In this work, tigapotide (PCK3145) was incorporated into novel nanocarriers based on polymeric, lipidic, and dendrimeric components, in order to maximize the advantages of the drug delivery process and possibly its biological properties. PCK3145 was incorporated into lipidic nanocarriers composed of Egg phosphatidylcholine (EggPC) and dipalmytoylphosphatidylcholine (DPPC) (EggPC:PCK3145 and DPPC:PCK3145, 9:0.2 molar ratio), into cationic liposomes composed of EggPC:SA:PCK3145 and DPPC:SA:PCK3145 (9:1:0.2 molar ratio) into complexes with the block polyelectrolyte (quaternized poly[3,5-bis(dimethylaminomethylene)hydroxystyrene]-b-poly(ethylene oxide) (QNPHOSEO) and finally into dendrimeric structures (i.e., PAMAM G4). Light scattering techniques are used in order to examine the size, the size distribution and the Z-potential of the nanocarriers in aqueous and biological media. Fluorescence spectroscopy was utilized in an attempt to extract information on the internal nanostructure and microenvironment of polyelectrolyte/PCK3145 aggregates. Therefore, these studies could be a rational roadmap for producing various effective nanocarriers in order to ameliorate the pharmacokinetic behavior and safety issues of antitumor and anticancer biomolecules

  19. Nature of the bifunctional chelating agent used for radioimmunotherapy with yttrium-88 monoclonal antibodies: critical factors in determining in vivo survival and organ toxicity

    Energy Technology Data Exchange (ETDEWEB)

    Kozak, R.W.; Raubitschek, A.; Mirzadeh, S.; Brechbiel, M.W.; Junghaus, R.; Gansow, O.A.; Waldmann, T.A. (Center for Biologics Evaluation and Research, FDA, Bethesda, MD (USA))

    1989-05-15

    One factor that is critical to the potential effectiveness of radioimmunotherapy is the design of radiometal-chelated antibodies that will be stable in vivo. Stability in vivo depends on the condition that both the chelate linkage and radiolabeling procedures not alter antibody specificity and biodistribution. In addition, synthesis and selection of the chelating agent is critical for each radiometal in order to prevent inappropriate release of the radiometal in vivo. In the present study, we compare the in vivo stability of seven radioimmunoconjugates that use different polyaminocarboxylate chelating agents to complex yttrium-88 to the mouse anti-human interleukin-2 receptor monoclonal antibody, anti-Tac. Chelate linkage and radiolabeling procedures did not alter the immunospecificity of anti-Tac. In order to assess whether yttrium was inappropriately released from the chelate-coupled antibody in vivo, iodine-131-labeled and yttrium-88 chelate-coupled antibodies were simultaneously administered to the same animals to correlate the decline in yttrium and radioiodinated antibody activity. The four stable yttrium-88 chelate-coupled antibodies studied displayed similar iodine-131 and yttrium-88 activity, indicating minimal elution of yttrium-88 from the complex. In contrast, the unstable yttrium-88 chelate-coupled antibodies had serum yttrium-88 activities that declined much more rapidly than their iodine-131 activities, suggesting loss of the radiolabel yttrium-88 from the chelate. Furthermore, high rates of yttrium-88 elution correlated with deposition in bone. Four chelating agents emerged as promising immunotherapeutic reagents: isothiocyanate benzyl DTPA and its derivatives 1B3M, MX, and 1M3B.

  20. A Randomized Phase 2 Trial of 177Lu Radiolabeled Anti-PSMA Monoclonal Antibody J591 in Patients with High-Risk Castrate, Biochemically Relapsed Prostate Cancer

    Science.gov (United States)

    2014-09-01

    Irene Karpenko Lauren Tyrell Olivera Calukovic Gillian Hodes June Greenberg Jessica Campbell PATIENTS AND THEIR FAMILIES Biostatistics...myelosuppression or need for >2 platelet (plt) transfusions, febrile neutropenia , or grade >2 non-heme toxicity following 177Lu- J591. PSA was assessed prior to...toxicity • Grade 4 neutropenia or thrombocytopenia > 14 days • Need for > 2 platelet transfusions or hemorrhage • Febrile neutropenia • > 3 week delay for

  1. A Randomized Phase 2 Trial of 177Lu Radiolabeled Anti-PSMA Monoclonal Antibody J591in Patients with High-Risk Castrate, Biochemically Relapsed Prostate Cancer

    Science.gov (United States)

    2012-09-01

    2010 and 2011 annual scientific meeting of the American Society of Clinical Oncologists  Manuscript detailing background and rationale for the...noncancerous causes, and 6.6% died from unknown causes [15]. A pooled analysis of salvage cryoablation demonstrated 54.5% 5-year actuarial biochemical

  2. A Randomized Phase 2 Trial of 177Lu Radiolabeled Anti-PSMA Monoclonal Antibody J591 in Patients With High-Risk Castrate, Biochemically Relapsed Prostate Cancer

    Science.gov (United States)

    2016-09-01

    agents Not applicable. 7  PRODUCTS:  Publications, conference papers , and presentations:  Journal publications. Nothing to report...Books or other non-periodical, one-time publications. Nothing to report.  Other publications, conference papers , and presentations. Nothing to...phosphate buffered saline containing not more than 1% Human Serum Albumin (HSA). All reagents used in the conjugation and purification of J591 are made

  3. A Randomized Phase 2 Trial of 177Lu Radiolabeled Anti-PSMA Monoclonal Antibody J591 in Patients With High-Risk Castrate, Biochemically Relapsed Prostate Cancer

    Science.gov (United States)

    2017-09-01

    on a federally funded study (as compared to pharmaceutical -sponsored). Therefore, after discussions with the site PI’s, additional key opinion...location (printed) APPENDIX C iv SCHEMA Informed Consent Screening Labs (CBC, chemistry, PSA, testosterone), CT/ MRI abd/pelvis, bone scan, CXR...111In-J591, continue ketoconazole, J591 scan Infusion of 177Lu-J591 x1, continue ketoconazole, J591 scan CT/ MRI abd/pelvis, bone scan, CXR q 6

  4. Elucidation of the critical epitope of an anti-EGFR monoclonal antibody EMab-134.

    Science.gov (United States)

    Kaneko, Mika K; Yamada, Shinji; Itai, Shunsuke; Chang, Yao-Wen; Nakamura, Takuro; Yanaka, Miyuki; Kato, Yukinari

    2018-07-01

    The epidermal growth factor receptor (EGFR) is a type-1 transmembrane receptor tyrosine kinase, which activates the downstream signaling cascades in many tumors, such as oral and lung cancers. We previously developed EMab-134, a novel anti-EGFR monoclonal antibody (mAb), which reacts with endogenous EGFR-expressing cancer cell lines and normal cells independent of glycosylation in Western blotting, flow cytometry, and immunohistochemical analysis. EMab-134 showed very high sensitivity (94.7%) to oral squamous cell carcinomas in immunohistochemical analysis. In this study, we performed enzyme-linked immunosorbent assay (ELISA), flow cytometry, and immunohistochemical analysis to determine the epitope of EMab-134. A blocking peptide (375-394 amino acids of EGFR) neutralized the EMab-134 reaction against oral cancer cells in flow cytometry and immunohistochemistry. The minimum epitope of EMab-134 was found to be the 377- RGDSFTHTPP -386 sequence. Our findings can be applied for the production of more functional anti-EGFR mAbs that in turn can be used for antitumor treatments.

  5. Elucidation of the critical epitope of an anti-EGFR monoclonal antibody EMab-134

    Directory of Open Access Journals (Sweden)

    Mika K. Kaneko

    2018-07-01

    Full Text Available The epidermal growth factor receptor (EGFR is a type-1 transmembrane receptor tyrosine kinase, which activates the downstream signaling cascades in many tumors, such as oral and lung cancers. We previously developed EMab-134, a novel anti-EGFR monoclonal antibody (mAb, which reacts with endogenous EGFR-expressing cancer cell lines and normal cells independent of glycosylation in Western blotting, flow cytometry, and immunohistochemical analysis. EMab-134 showed very high sensitivity (94.7% to oral squamous cell carcinomas in immunohistochemical analysis. In this study, we performed enzyme-linked immunosorbent assay (ELISA, flow cytometry, and immunohistochemical analysis to determine the epitope of EMab-134. A blocking peptide (375–394 amino acids of EGFR neutralized the EMab-134 reaction against oral cancer cells in flow cytometry and immunohistochemistry. The minimum epitope of EMab-134 was found to be the 377-RGDSFTHTPP−386 sequence. Our findings can be applied for the production of more functional anti-EGFR mAbs that in turn can be used for antitumor treatments.

  6. Biodistribution and pharmacokinetic of 1E10 monoclonal antibody after subcutaneous administration in healthy mice

    International Nuclear Information System (INIS)

    León, M; Hernández, I; Aldana, L; Ayra, F; Castro, Y; Leyva, R; García, L; Casaco, A

    2016-01-01

    To evaluate biodistribution and pharmacokinetic of the 1E10, the molecule was radio labelled with 125I and incorporated into a cold antibody formulation. Isotopic labeling was carried out by means of standardized methods.Introduction:1E10 monoclonal antibody was developed at Centre of Molecular Immunology (CIM) as antitumoral drug with proved efficacy in experimental models. In the present investigation, biodistribution and pharmacokinetic studies were conducted with the help of radio isotopic labeling. Materials and methods: 1E10 was supplied by CIM and labeled with 125I by the iodogen method. To male Balb/c mice from CENPALAB a single subcutaneous administration of 1 mg/kg was performed in the supra scapular region and accommodated in metabolic cages during experiments. Blood samples were taken alternating five groups of three animals according with a sparse data design. Biodistribution was carried out by direct organ sampling and radioactive counting. Pharmacokinetic was performed by compartmental analysis. Urine and faces were collected at regular time intervals. Results: Observed pharmacokinetic behaviour is typical of an immunoglobulin in the assay system used, showing a slow clearance and a small volume of distribution. Biodistribution shows no preference for any sampled organs or tissues. Only a high relative uptake was observed in axillary and brachial lymph nodes close to administration site. (author)

  7. Radiolabeling procedure, quality control and stability of 99mTc-labeled chondroitin sulfate: A new approach of targeting osteoarthritis

    International Nuclear Information System (INIS)

    Sobal, Grazyna; Menzel, Ernst Johannes; Sinzinger, Helmut

    2008-01-01

    Chondroitin sulfate (CS) is an endogenous component of cartilage which could determine osteoarthritis after radiolabeling. Radiolabeling was performed by 99m TcO 4 - /tin method. We found that pH is a limiting factor. At pH 6.2 in 0.05 M Na acetate buffer 32.8% colloid was formed, at pH 5.0 in 0.5 M Na acetate, in our methodology only 4.7% colloid. The tracer was highly stable. We conclude that 99m TcCS could be a promising imaging agent of osteoarthritis due to simple radiolabeling and high stability

  8. 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

  9. 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)

  10. 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

  11. Radioimaging of human mammary carcinoma xenografts in nude mice with a new monoclonal antibody

    International Nuclear Information System (INIS)

    Senekowitsch, R.; Bode, W.; Kriegel, H.; Reidel, G.; Pabst, H.W.

    1986-01-01

    A female Wistar rat aged 33 days was immunized by repeated intraperitoneal injections of a cell suspension of mammary carcinoma for eight months. Spleen cells of the immunized rat were then fused with X63-Ag8.653, a mouse myeloma line. Hybridoma supernatants were screened by ELISA using cells of mammary carcinoma (MaCa) as target cells. Initially 72 hybridomas showed positive response with MaCa cells, but no cross-reaction with normal mammary tissue was seen. Clone Ma 10-11 was chosen for its stable growth in vitro and in ascitic fluid. Monoclonal antibody obtained from ascitic fluid induced by intraperitoneal injection of 10 7 hybridoma cell into BALB/c-nu/nu mice was separated from albumin and transferrin. After separation only one band positioned at 155000 MW on SDS-PAGE slabs was detected. Radiolabeling with 131 I was achieved with the Iodogen method, the efficiency of labeling was 88%. 1.85 MBq of the intact labeled rat antibody were injected into nude mice xenografted with human mammary carcinoma and scintigrams were obtained every 48 hours p.i. up to 15 days. Scintigraphic images permitted tumor detection at 3 days p.i., but good tumor localization needed 8 days p.i.. The tumor-to-blood ratios calculated after dissection of tumor-bearing mice in groups of 3 increased from 0.97 at day 3 to 3 at day 15 p.i.. No uptake of the antibody in other organs was found. The half-life of the whole body clearance of the rat immunoglobulin was 36 h. This is significantly shorter than the half-life found for mouse immunoglobulin in nude mice. (Author)

  12. 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.

  13. Production, Isolation and Radiolabeling Methods for 211AT- Labeling of Biomolecules

    International Nuclear Information System (INIS)

    Wilbur, D.S.; Hamlin, D.K.; Chyan, M.

    2009-01-01

    Targeted alpha therapy with 211 At-labeled compounds holds great promise for treatment of cancer, particularly compartmentalized cancer (e.g. ovarian cancer), minimal residual cancer after surgery and metastatic disease. Unfortunately, 211 At has limited availability and, due to its unique nature, has the potential to be readily dissociated from the cancer-targeting agents used in vivo. Finding methods to circumvent these two problems has occupied a large amount of our efforts over the past few years. 211 At is produced at the University of Washington on a Scanditronix MC-50 using a 28 MeV alpha beam. Our initial preclinical studies were conducted using a small target assembly with irradiations of a 10 □ A alpha beam, but our desire to ultimately conduct clinical studies led to the design and installation of a new target assembly that had much larger irradiation surface and would withstand beam energies of 50 □A or more. Prior to this upgrade, 211 At was efficiently isolated (60-80%) from the irradiated aluminum-backed bismuth targets by dry distillation at 650 o C. However, the dry distillation method gave low recovery yields (e.g. 10-40%) when the much larger new targets were used. After some attempts to improve the distillation yields, we have more recently conducted a wet chemistry approach to the 211 At isolation. While this method still needs to be optimized, it has provided good recovery (60-90%) of the 211 At. Our radiolabeling methods have undergone a similar transition in the past few years. Until recently our 211 At studies were limited to the use of intact monoclonal antibodies (MAb) labeled using conjugates containing aryl-astatine derivatives due to the deastatination of more rapidly metabolized targeting biomolecules. This limitation made it all but impossible to label important biomolecules such as MAb fragments, engineered proteins, peptides and small molecules. This critical shortcoming of labeling methods for 211 At led to our investigating

  14. [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.

  15. 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

  16. 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.

  17. 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.

  18. 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.

  19. An Alternate, Egg-Free Radiolabeled Meal Formulation for Gastric-Emptying Scintigraphy.

    Science.gov (United States)

    Garrigue, Philippe; Bodin-Hullin, Aurore; Gonzalez, Sandra; Sala, Quentin; Guillet, Benjamin

    2017-07-01

    Tc-radiolabeled scrambled eggs (SEs) are most often used as the ingested solid phase for gastric-emptying scintigraphy, leading egg-reluctant patients to avoid the examination. We formulated and validated 2 egg-free alternate meals, in the absence of any commercialized formulation: chocolate mug cake (MC) and scrambled tofu (ST). Six healthy volunteers underwent gastric-emptying scintigraphy after ingesting Tc-radiolabeled MC, ST, or SE. Gastric retention indexes did not change significantly between formulations (% of overtime variation to SE: MC 7.75% ± 7.1%, ST 7.17% ± 5.8%; P = 0.6618, not statistically significant), suggesting MC and ST as interesting egg-free alternatives.

  20. Purification of radiolabeled RNA using sephadex G-15 or G-50 chromatography

    International Nuclear Information System (INIS)

    Yoo, Beong Gyu; Lee, Jong Seok

    1998-01-01

    We attempted to purify radiolabeled RNA using Sephadex G-15 and G-50 chromatography instead of commercial RNA purification kit. In the Sephadex G-15 chromatography the major portion of RNA was eluted in the fractions ranging from 3rd to 5th whereas broad elution profile of RNA was obtained from the Sephadex G-50 chromatography. The elution profile and purity of RNA obtained from Sephadex G-15 chromatography was very similar to that by commercial RNA purification kit. Furthermore, operating time required for purification of RNA by Sephadex G-15 was rather smaller than that by commercial kit. Overall results suggest that the purification of radiolabeled RNA using Sephadex G-15 is more money and time saving than using commercial RNA purification kit

  1. Study of pharmacokinetics and biodistribution of radiolabelled receptor specific peptides in laboratory animals

    International Nuclear Information System (INIS)

    Laznickova, A.; Laznicek, M.; Trejtnar, F.; Maecke, H.R.; Mather, S.J.

    2001-01-01

    Somatostatin analogues labelled with different radionuclides could be employed for visualization or treatment of somatostatin receptor-positive tumours. An octapeptide 111 In [DTPA] octreotide is a synthetic radiolabelled somatostatin analogue which is currently in clinical use for detecting small neuroendocrine tumours and metastases not detectable by conventional means. However, several other somatostatin analogues have been under development and testing. The aim of this study was to radiolabel selected somatostatin receptor-binding octapeptides by different radionuclides and to report the results of their biodistribution in rats. The study was focused on the direct labelling of vapreotide (RC-160) with 99m Tc, on the conjugates of octreotide with DFO (desferrioxamine) for labelling with 67 Ga, and on the conjugates of octreotide and TOC with DOTA (tetraazacyclo-dodecane tetraacetic acid) for labelling with 88 Y. In the present study, 88 Y isotope instead of 90 Y was used as a label as 88 Y exhibits a longer half life of decay and emits gamma radiation which can be much more easily detected in biological samples than beta emission. The labelling of octreotide analogues with metal radionuclides using derived bifunctional chelates was simple, straightforward and consistently resulted in high radiochemical purity of the product. On the other hand, the application of the direct labelling method for labelling of RC-160 with 99m Tc was difficult because all procedures had to be made under nitrogen atmosphere and an attainment of high yield proved to be highly dependent on the accurate observation of reaction conditions. The labelling efficiency makes an immediate use of the radiolabelled RC-160 for biological studies impossible and it is necessary to involve the purification step into the labelling procedure. All radiolabelled receptor specific peptides under study exhibited rapid radioactivity clearance from the blood and most organs and tissues. On the other hand

  2. Technical Report (Final): Development of Solid State Reagents for Preparing Radiolabeled Imaging Agents

    Energy Technology Data Exchange (ETDEWEB)

    Kabalka, George W

    2011-05-20

    The goal of this research was on the development of new, rapid, and efficient synthetic methods for incorporating short-lived radionuclides into agents of use in measuring dynamic processes. The initial project period (Year 1) was focused on the preparation of stable, solid state precursors that could be used to efficiently incorporate short-lived radioisotopes into small molecules of use in biological applications (environmental, plant, and animal). The investigation included development and evaluation of new methods for preparing carbon-carbon and carbon-halogen bonds for use in constructing the substrates to be radiolabeled. The second phase (Year 2) was focused on developing isotope incorporation techniques using the stable, boronated polymeric precursors. The final phase (Year 3), was focused on the preparation of specific radiolabeled agents and evaluation of their biodistribution using micro-PET and micro-SPECT. In addition, we began the development of a new series of polymeric borane reagents based on polyethylene glycol backbones.

  3. Langmuir hydrogen dissociation approach in radiolabeling carbon nanotubes and graphene oxide

    International Nuclear Information System (INIS)

    Badun, Gennadii A.; Chernysheva, Maria G.; Eremina, Elena A.; Egorov, Alexander V.; Grigorieva, Anastasia V.

    2016-01-01

    Carbon-based nanomaterials have piqued the interest of several researchers. At the same time, radioactive labeling is a powerful tool for studying processes in different systems, including biological and organic; however, the introduction of radioactive isotopes into carbon-based nanomaterial remains a great challenge. We have used the Langmuir hydrogen dissociation method to introduce tritium in single-walled carbon nanotubes and graphene oxide. The technique allows us to achieve a specific radioactivity of 107 and 27 Ci/g for single-layer graphene oxide and single-walled carbon nanotubes, respectively. Based on the analysis of characteristic Raman modes at 1350 and 1580 cm -1 , a minimal amount of structural changes to the nanomaterials due to radiolabeling was observed. The availability of a simple, nondestructive, and economic technique for the introduction of radiolabels to single-walled carbon nanotubes and graphene oxide will ultimately expand the applicability of these materials.

  4. Radiolabeled porphyrin versus gallium-67 citrate for the detection of human melanoma in athymic mice

    International Nuclear Information System (INIS)

    Maric, N.; Chan, S. Ming; Hoffer, P.B.; Duray, P.

    1987-01-01

    We performed the biodistribution and imaging studies of 111 In and 67 Ga labeled tetra(4-N-methylpyridyl) porphine, (T4NMPYP), and compared it to that of 67 Ga citrate in athymic mice bearing a human melanoma xenograft. The biodistribution results of both 111 In and 67 Ga labeled T4NMPYP (3, 6, 24, and 48 hours) were similar but differed from that of 67 Ga citrate (48 hours). The optimum tumor uptake of both radiolabeled porphyrins was at 6 hours postinjection and was lower than the tumor uptake of 67 Ga citrate at 48 hours postinjection. Kidney was the only organ showing higher uptake of radiolabeled porphyrin compared to that of 67 Ga citrate. The imaging studies performed with 111 In T4NMPYP and 67 Ga citrate correspond to the biodistribution results. Osteomyelitis present in one mouse showed good localization of 111 In T4NMPYP. 15 refs., 3 figs., 5 tabs

  5. Langmuir hydrogen dissociation approach in radiolabeling carbon nanotubes and graphene oxide

    Energy Technology Data Exchange (ETDEWEB)

    Badun, Gennadii A.; Chernysheva, Maria G.; Eremina, Elena A.; Egorov, Alexander V. [Lomonosov Moscow State Univ. (Russian Federation). Dept. of Chemistry; Grigorieva, Anastasia V. [Lomonosov Moscow State Univ., Moscow (Russian Federation). Dept. of Materials Science

    2016-11-01

    Carbon-based nanomaterials have piqued the interest of several researchers. At the same time, radioactive labeling is a powerful tool for studying processes in different systems, including biological and organic; however, the introduction of radioactive isotopes into carbon-based nanomaterial remains a great challenge. We have used the Langmuir hydrogen dissociation method to introduce tritium in single-walled carbon nanotubes and graphene oxide. The technique allows us to achieve a specific radioactivity of 107 and 27 Ci/g for single-layer graphene oxide and single-walled carbon nanotubes, respectively. Based on the analysis of characteristic Raman modes at 1350 and 1580 cm{sup -1}, a minimal amount of structural changes to the nanomaterials due to radiolabeling was observed. The availability of a simple, nondestructive, and economic technique for the introduction of radiolabels to single-walled carbon nanotubes and graphene oxide will ultimately expand the applicability of these materials.

  6. Preparation and biodistribution of {sup 59}Fe-radiolabelled iron oxide nanoparticles

    Energy Technology Data Exchange (ETDEWEB)

    Pospisilova, Martina, E-mail: martinapospisilova@gmail.com; Zapotocky, Vojtech; Nesporova, Kristina [Contipro a.s (Czech Republic); Laznicek, Milan; Laznickova, Alice [Charles University, Faculty of Pharmacy in Hradec Králové (Czech Republic); Zidek, Ondrej; Cepa, Martin; Vagnerova, Hana; Velebny, Vladimir [Contipro a.s (Czech Republic)

    2017-02-15

    We report on the {sup 59}Fe radiolabelling of iron oxide nanoparticle cores through post-synthetic isotope exchange ({sup 59}Fe-IONP{sub ex}) and precursor labelling ({sup 59}Fe-IONP{sub pre}). Scanning electron microscopy and dynamic light scattering measurements showed no impact of radiolabelling on nanoparticle size or morphology. While incorporation efficiencies of these methods are comparable—83 and 90% for precursor labelling and post-synthetic isotope exchange, respectively—{sup 59}Fe-IONP{sub pre} exhibited much higher radiochemical stability in citrated human plasma. Quantitative ex vivo biodistribution study of {sup 59}Fe-IONP{sub pre} coated with triethylene glycol was performed in Wistar rats. Following the intravenous administration, high {sup 59}Fe concentration was observed in the lung and the organs of the reticuloendothelial system such as the liver, the spleen and the femur.

  7. Synthesis, radiolabeling and biodistribution of a new opioid glucuronide derivative. Ethyl-morphine glucuronide (em-glu)

    International Nuclear Information System (INIS)

    Enginar, H.

    2012-01-01

    In current study, ethyl-morphine (em) was synthesized from the morphine and glucuronidated via enzymatic mechanism. The conjugated glucuronide ethyl-morphine (em-glu) was radiolabeled with 131 I using iodogen method. The quality control studies of radiolabeled compound ( 131 I-em-glu) were done with Thin Layer Radio Chromatography to confirm the radiolabeling efficiency. Biodistribution studies of 131 I labeled em-glu were run on healthy male Albino Wistar rats. The distribution figures demonstrated that 131 I-em-glu was eliminated through the small intestine, large intestine and accumulated in urinary bladder both receptor blocked and unblocked biodistribution studies. A greater uptake of the radiolabeled substance was observed in the m.pons, hypothalamus and mid brain than in the other branches of the rats' brains. (author)

  8. Antitumoral activity of marine organism; Actividad antitumoral de los organismos marinos

    Energy Technology Data Exchange (ETDEWEB)

    Valdes Iglesias, O [Centro de Bioproductos Marinos, La Habana (Cuba); Perez Gil, R; Colom, Y [Instituno Nacional de Oncologia y Radiobiologia (INOR), La Habana (Cuba)

    2010-07-01

    The study of the natural products from marine organism constitute a relatively recent scientific researcher field with high potentialities tanking in consideration that the oceans cover the three of the four parts of the earth. Poryphera and Bryozoans have been the Phylum more studied owning to the vulnerability, their soft body, their habitat on rocks, their slow movement and bright colors, for these reason these organisms are able to produce chemical substances as defense methods against depredators. Same mechanism is exhibit by the seaweeds with the production of secondary metabolites . In the present communication are exposed the main results obtained on the world a Cuba until the present in the looking for of substances with antitumor action from marine organism.

  9. 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...

  10. 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.)

  11. 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...

  12. Preparation and characterization of high-specific activity radiolabeled 50 S measles virus RNA

    International Nuclear Information System (INIS)

    Spruance, S.L.; Ashton, B.N.; Smith, C.B.

    1980-01-01

    A method is described to radiolabeled measles virus RNA for hybridization studies. Tritiated nucleosides were added to the media of measles virus infected Vero cells and negative-strand (genome) RNA with a specific activity of 6X10 5 c.p.m./μg was purified from viral nucleocapsids. 50 S RNA was the sole RNA present in nucleocapsids and self-annealed to 50% due to the presence of 25% 50 S plus-strands (anti-genomes). (Auth.)

  13. Some problems associated with radiolabeling surface antigens on helminth parasites: a brief review

    Energy Technology Data Exchange (ETDEWEB)

    Hayunga, E.G. (Division of Tropical Public Health, Department of Preventive Medicine and Biometrics, Uniformed Services University of the Health Sciences, Bethesda, MD (USA)); Murrell, K.D. (Agricultural Research Service, Beltsville, MD (USA))

    1982-06-01

    Recent developments in technology have facilitated substantial advances in the characterization of surface antigens from a wide variety of both normal and neoplastic cells. However, the immunochemistry of parasites has lagged behind. Efforts to apply conventional radiolabeling methods to helminths have not always been successful. Experimental work with Schistosoma mansoni is reviewed to illustrate common problems encountered in surface labeling studies. These findings should provide insight for the future investigation of other helminth species.

  14. Some problems associated with radiolabeling surface antigens on helminth parasites: a brief review

    International Nuclear Information System (INIS)

    Hayunga, E.G.; Murrell, K.D.

    1982-01-01

    Recent developments in technology have facilitated substantial advances in the characterization of surface antigens from a wide variety of both normal and neoplastic cells. However, the immunochemistry of parasites has lagged behind. Efforts to apply conventional radiolabeling methods to helminths have not always been successful. Experimental work with Schistosoma mansoni is reviewed to illustrate common problems encountered in surface labeling studies. These findings should provide insight for the future investigation of other helminth species. (Auth.)

  15. Tumor affinity of radiolabeled peanut agglutinin compared with that of Ga-67 citrate in animal models

    International Nuclear Information System (INIS)

    Yokoyama, K.; Aburano, T.; Watanabe, N.; Kawabata, S.; Ishida, H.; Mukai, K.; Tonami, N.; Hisada, K.

    1985-01-01

    Peanut agglutinin (PNA) binds avidly to the immunodominant group of the tumor associated T antigen. The purpose of this study was to evaluate oncodiagnostic potential of radiolabeled PNA in animal models. PNA was labeled with I-125 or I-131 by Iodogen and also with In-111 by cyclic DTPA anhydride. The biological activity of PNA was examined by a hemaglutination titer with a photometer before and after labeling. Animal tumor models used were Lewis Lung Cancer(LLC), B-16 Melanotic Melanoma(MM), Yoshida Sarcoma(YS), Ehrlich Ascites Tumor(EAT and Hepatoma AH109A(HAH). Inflammatory tissue induced by turpentine oil was used as an abscess model. Serial scintigraphic images were obtained following IV injections of 100 μCi of I-131 or In-111-DTPA-PNA. The tumor affinity of Ga-67 citrate was studied to compare that of radiolabeled PNA. Tissue biodistribution was studied in EAT bearing mice. All of these tumor models except HAH were clearly visible by radiolabeled PNA without subtraction techniques. In the models of LLC and EAT, PNA showed the better accumulation into the tumor tissue than Ga-67 citrate. In YS and MM, PNA represented almost the same accumulation as Ga-67 citrate. The localization of PNA into abscess tissue wasn't found although Ga-67 citrate markedly accumulated into abscess tissue as well as tumor tissue. The clearance of PNA from tumor was slower than those from any other organs. Tumor to muscle ratio was 5.1 at 48hrs. and tumor to blood ratio increased with time to 2.3 at 96hrs. These results suggested that radiolabeled PNA may have a potential in the detection of tumor

  16. Intrinsically radiolabelled [59Fe]-SPIONs for dual MRI/radionuclide detection

    OpenAIRE

    Hoffman, David; Sun, Minghao; Yang, Likun; McDonagh, Philip R; Corwin, Frank; Sundaresan, Gobalakrishnan; Wang, Li; Vijayaragavan, Vimalan; Thadigiri, Celina; Lamichhane, Narottam; Zweit, Jamal

    2014-01-01

    Towards the development of iron oxide nanoparticles with intrinsically incorporated radionuclides for dual Positron Emission Tomography/Magnetic Resonance Imaging (PET/MRI) and more recently of Single Photon Emission Computed Tomography/Magnetic Resonance Imaging (SPECT/MRI), we have developed intrinsically radiolabeled [59Fe]-superparamagnetic iron oxide nanoparticles ([59Fe]-SPIONs) as a proof of concept for an intrinsic dual probe strategy. 59Fe was incorporated into Fe3O4 nanoparticle cry...

  17. Experimental study of capacity of the blood blow of spinal cord using radiolabelling microspbere technique

    International Nuclear Information System (INIS)

    Hu Xuan; Li Rui

    2007-01-01

    Objective In order to study the relation ship between local blood flow and neurofunction at the later stage of spinal injury. Method: Measured the capacity of the local blood flow in the spinal cord injury by the radiolabelling microsphere technique and scored the nervus function grade. Result: There are no correlation between the local blood flow and the nervus function. Conclusion: It is obvious that the increase of the local blood supply can't reflect the nervus function. (authors)

  18. Radiolabelled peptides for tumour therapy: current status and future directions. Plenary lecture at the EANM 2002

    International Nuclear Information System (INIS)

    Jong, Marion de; Kwekkeboom, Dik; Valkema, Roelf; Krenning, Eric P.

    2003-01-01

    On their plasma membranes, cells express receptor proteins with high affinity for regulatory peptides, such as somatostatin. Changes in the density of these receptors during disease, e.g. overexpression in many tumours, provide the basis for new imaging methods. The first peptide analogues successfully applied for visualisation of receptor-positive tumours were radiolabelled somatostatin analogues. The next step was to label these analogues with therapeutic radionuclides for peptide receptor radionuclide therapy (PRRT). Results from preclinical and clinical multicentre studies have already shown an effective therapeutic response when using radiolabelled somatostatin analogues to treat receptor-positive tumours. Infusion of positively charged amino acids reduces kidney uptake, enlarging the therapeutic window. For PRRT of CCK-B receptor-positive tumours, such as medullary thyroid carcinoma, radiolabelled minigastrin analogues are currently being successfully applied. The combination of different therapy modalities holds interest as a means of improving the clinical therapeutic effects of radiolabelled peptides. The combination of different radionuclides, such as 177 Lu- and 90 Y-labelled somatostatin analogues, to reach a wider tumour region of high curability, has been described. A variety of other peptide-based radioligands, such as bombesin and NPY(Y 1 ) analogues, receptors for which are expressed on common cancers such as prostate and breast cancer, are currently under development and in different phases of (pre)clinical investigation. Multi-receptor tumour targeting using the combination of bombesin and NPY(Y 1 ) analogues is promising for scintigraphy and PRRT of breast carcinomas and their lymph node metastases. (orig.)

  19. Radiolabeled antibody in the detection of infection using endocarditis as a model

    International Nuclear Information System (INIS)

    Mishkin, F.S.; Wong, D.W.; Dhawan, V.K.; Reese, I.C.; Thadepalli, H.

    1983-01-01

    The authors have examined a method to detect infections using radiolabeled antibodies. Staphylococcal endocarditis was chosen as a model because it poses a common clinical diagnostic problem. The experiments demonstrate that biologically active antibodies may be extracted and efficiently labeled by a relatively simple process. This has the potential to make the specificity of the in vivo antigen-antibody reaction available through the use of autologously extracted, labeled γ-globulin

  20. Albumin-derived peptides efficiently reduce renal uptake of radiolabelled peptides

    International Nuclear Information System (INIS)

    Vegt, Erik; Eek, Annemarie; Oyen, Wim J.G.; Gotthardt, Martin; Boerman, Otto C.; Jong, Marion de

    2010-01-01

    In peptide-receptor radionuclide therapy (PRRT), the maximum activity dose that can safely be administered is limited by high renal uptake and retention of radiolabelled peptides. The kidney radiation dose can be reduced by coinfusion of agents that competitively inhibit the reabsorption of radiolabelled peptides, such as positively charged amino acids, Gelofusine, or trypsinised albumin. The aim of this study was to identify more specific and potent inhibitors of the kidney reabsorption of radiolabelled peptides, based on albumin. Albumin was fragmented using cyanogen bromide and six albumin-derived peptides with different numbers of electric charges were selected and synthesised. The effect of albumin fragments (FRALB-C) and selected albumin-derived peptides on the internalisation of 111 In-albumin, 111 In-minigastrin, 111 In-exendin and 111 In-octreotide by megalin-expressing cells was assessed. In rats, the effect of Gelofusine and albumin-derived peptides on the renal uptake and biodistribution of 111 In-minigastrin, 111 In-exendin and 111 In-octreotide was determined. FRALB-C significantly reduced the uptake of all radiolabelled peptides in vitro. The albumin-derived peptides showed different potencies in reducing the uptake of 111 In-albumin, 111 In-exendin and 111 In-minigastrin in vitro. The most efficient albumin-derived peptide (peptide 6), was selected for in vivo testing. In rats, 5 mg of peptide 6 very efficiently inhibited the renal uptake of 111 In-minigastrin, by 88%. Uptake of 111 In-exendin and 111 In-octreotide was reduced by 26 and 33%, respectively. The albumin-derived peptide 6 efficiently inhibited the renal reabsorption of 111 In-minigastrin, 111 In-exendin and 111 In-octreotide and is a promising candidate for kidney protection in PRRT. (orig.)

  1. Radiolabeling and in vitro evaluation of 99mTc-methotrexate on breast cancer cell line

    International Nuclear Information System (INIS)

    Emre Ozgenc; Meliha Ekinci; Derya Ilem-Ozdemir; Evren Gundogdu; Makbule Asikoglu

    2016-01-01

    In the present study 99m Tc-MTX was prepared with high labeling yield by a new simple and easy formulation method. According to cell culture studies, 99m Tc- MTX incorporated with both MCF-7 and CRL8798 cells, with significant differences in the uptake percentages. Since 99m Tc-MTX highly uptake in cancer cell line, the results demonstrated that radiolabeled MTX may be promising for breast cancer diagnosis of oncological patients. (author)

  2. Fractionated photothermal antitumor therapy with multidye nanoparticles

    Directory of Open Access Journals (Sweden)

    Gutwein LG

    2012-01-01

    Full Text Available Luke G Gutwein1, Amit K Singh2, Megan A Hahn2, Michael C Rule3, Jacquelyn A Knapik4, Brij M Moudgil2, Scott C Brown2, Stephen R Grobmyer11Division of Surgical Oncology, Department of Surgery, College of Medicine, 2Particle Engineering Research Center, 3Cell and Tissue Analysis Core, McKnight Brain Institute, 4Department of Pathology, University of Florida, Gainesville, FL, USAPurpose: Photothermal therapy is an emerging cancer treatment paradigm which involves highly localized heating and killing of tumor cells, due to the presence of nanomaterials that can strongly absorb near-infrared (NIR light. In addition to having deep penetration depths in tissue, NIR light is innocuous to normal cells. Little is known currently about the fate of nanomaterials post photothermal ablation and the implications thereof. The purpose of this investigation was to define the intratumoral fate of nanoparticles (NPs after photothermal therapy in vivo and characterize the use of novel multidye theranostic NPs (MDT-NPs for fractionated photothermal antitumor therapy.Methods: The photothermal and fluorescent properties of MDT-NPs were first characterized. To investigate the fate of nanomaterials following photothermal ablation in vivo, novel MDT-NPs and a murine mammary tumor model were used. Intratumoral injection of MDT-NPs and real-time fluorescence imaging before and after fractionated photothermal therapy was performed to study the intratumoral fate of MDT-NPs. Gross tumor and histological changes were made comparing MDT-NP treated and control tumor-bearing mice.Results: The dual dye-loaded mesoporous NPs (ie, MDT-NPs; circa 100 nm retained both their NIR absorbing and NIR fluorescent capabilities after photoactivation. In vivo MDT-NPs remained localized in the intratumoral position after photothermal ablation. With fractionated photothermal therapy, there was significant treatment effect observed macroscopically (P = 0.026 in experimental tumor-bearing mice

  3. Recent Advances in the Development and Application of Radiolabeled Kinase Inhibitors for PET Imaging

    Directory of Open Access Journals (Sweden)

    Vadim Bernard-Gauthier

    2015-12-01

    Full Text Available Over the last 20 years, intensive investigation and multiple clinical successes targeting protein kinases, mostly for cancer treatment, have identified small molecule kinase inhibitors as a prominent therapeutic class. In the course of those investigations, radiolabeled kinase inhibitors for positron emission tomography (PET imaging have been synthesized and evaluated as diagnostic imaging probes for cancer characterization. Given that inhibitor coverage of the kinome is continuously expanding, in vivo PET imaging will likely find increasing applications for therapy monitoring and receptor density studies both in- and outside of oncological conditions. Early investigated radiolabeled inhibitors, which are mostly based on clinically approved tyrosine kinase inhibitor (TKI isotopologues, have now entered clinical trials. Novel radioligands for cancer and PET neuroimaging originating from novel but relevant target kinases are currently being explored in preclinical studies. This article reviews the literature involving radiotracer design, radiochemistry approaches, biological tracer evaluation and nuclear imaging results of radiolabeled kinase inhibitors for PET reported between 2010 and mid-2015. Aspects regarding the usefulness of pursuing selective vs. promiscuous inhibitor scaffolds and the inherent challenges associated with intracellular enzyme imaging will be discussed.

  4. Selective radiolabeling of cell surface proteins to a high specific activity

    International Nuclear Information System (INIS)

    Thompson, J.A.; Lau, A.L.; Cunningham, D.D.

    1987-01-01

    A procedure was developed for selective radiolabeling of membrane proteins on cells to higher specific activities than possible with available techniques. Cell surface amino groups were derivatized with 125 I-(hydroxyphenyl)propionyl groups via 125 I-sulfosuccinimidyl (hydroxyphenyl)propionate ( 125 II-sulfo-SHPP). This reagent preferentially labeled membrane proteins exposed at the cell surface of erythrocytes as assessed by the degree of radiolabel incorporation into erythrocyte ghost proteins and hemoglobin. Comparison with the lactoperoxidase-[ 125 I]iodide labeling technique revealed that 125 I-sulfo-SHPP labeled cell surface proteins to a much higher specific activity and hemoglobin to a much lower specific activity. Additionally, this reagent was used for selective radiolabeling of membrane proteins on the cytoplasmic face of the plasma membrane by blocking exofacial amino groups with uniodinated sulfo-SHPP, lysing the cells, and then incubating them with 125 I-sulfo-SHPP. Exclusive labeling of either side of the plasma membrane was demonstrated by the labeling of some marker proteins with well-defined spacial orientations on erythroctyes. Transmembrane proteins such as the epidermal growth factor receptor on cultured cells could also be labeled differentially from either side of the plasma membrane

  5. Radiolabeling of VEGF165 with 99mTc to evaluate VEGFR expression in tumor angiogenesis.

    Science.gov (United States)

    Galli, Filippo; Artico, Marco; Taurone, Samanta; Manni, Isabella; Bianchi, Enrica; Piaggio, Giulia; Weintraub, Bruce D; Szkudlinski, Mariusz W; Agostinelli, Enzo; Dierckx, Rudi A J O; Signore, Alberto

    2017-06-01

    Angiogenesis is the main process responsible for tumor growth and metastatization. The principal effector of such mechanism is the vascular endothelial growth factor (VEGF) secreted by cancer cells and other components of tumor microenvironment. Radiolabeled VEGF analogues may provide a useful tool to noninvasively image tumor lesions and evaluate the efficacy of anti-angiogenic drugs that block the VEGFR pathway. Aim of the present study was to radiolabel the human VEGF165 analogue with 99mTechnetium (99mTc) and to evaluate the expression of VEGFR in both cancer and endothelial cells in the tumor microenvironment. 99mTc-VEGF showed in vitro binding to HUVEC cells and in vivo to xenograft tumors in mice (ARO, K1 and HT29). By comparing in vivo data with immunohistochemical analysis of excised tumors we found an inverse correlation between 99mTc-VEGF165 uptake and VEGF histologically detected, but a positive correlation with VEGF receptor expression (VEGFR1). Results of our studies indicate that endogenous VEGF production by cancer cells and other cells of tumor microenvironment should be taken in consideration when performing scintigraphy with radiolabeled VEGF, because of possible false negative results due to saturation of VEGFRs.

  6. Metabolic comparison of radiolabeled aniline- and phenol-phthaleins with 131I

    International Nuclear Information System (INIS)

    Avcibasi, Ugur; Avcibasi, Nesibe; Unak, Turan; Unak, Perihan; Mueftueler, Fazilet Zuemruet; Yildirim, Yeliz; Dincalp, Haluk; Guemueser, Fikriye Guel; Dursun, Ebru Rueksen

    2008-01-01

    The metabolic comparison of aniline- and phenol-phthaleins radiolabeled with 131 I ( 131 I-APH and 131 I-PPH, respectively) has been investigated in this study. To compare the metabolic behavior of these phthaleins and their glucuronide conjugates radiolabeled with 131 I, scintigraphic and biodistributional techniques were applied using male Albino rabbits. The results obtained have shown that these compounds were successfully radioiodinated with a radioiodination yield of about 100%. Maximum uptakes of 131 I-APH and 131 I-PPH, which were metabolized as N- and O-glucuronides, were observed within 2 h in the bladder and in the small intestine, respectively. In the case of verification of considerably up taking of these compounds also by tumors developed in the small intestine and in the bladder tissues, these results can be expected to be encouraging to test these compounds, which will be radiolabeled with other radioiodines such as 125 I, 123 I and 124 I as imaging and therapeutic agents in nuclear medical applications

  7. Metabolic comparison of radiolabeled aniline- and phenol-phthaleins with (131)I.

    Science.gov (United States)

    Avcibaşi, Uğur; Avcibaşi, Nesibe; Unak, Turan; Unak, Perihan; Müftüler, Fazilet Zümrüt; Yildirim, Yeliz; Dinçalp, Haluk; Gümüşer, Fikriye Gül; Dursun, Ebru Rükşen

    2008-05-01

    The metabolic comparison of aniline- and phenol-phthaleins radiolabeled with (131)I ((131)I-APH and (131)I-PPH, respectively) has been investigated in this study. To compare the metabolic behavior of these phthaleins and their glucuronide conjugates radiolabeled with (131)I, scintigraphic and biodistributional techniques were applied using male Albino rabbits. The results obtained have shown that these compounds were successfully radioiodinated with a radioiodination yield of about 100%. Maximum uptakes of (131)I-APH and (131)I-PPH, which were metabolized as N- and O-glucuronides, were observed within 2 h in the bladder and in the small intestine, respectively. In the case of verification of considerably up taking of these compounds also by tumors developed in the small intestine and in the bladder tissues, these results can be expected to be encouraging to test these compounds, which will be radiolabeled with other radioiodines such as (125)I, (123)I and (124)I as imaging and therapeutic agents in nuclear medical applications.

  8. Development of radiolabeled mannose-dextran conjugates for sentinel lymph node detection

    International Nuclear Information System (INIS)

    Fernandez Nunez, Eutimio Gustavo

    2011-01-01

    Early diagnosis of tumors and metastasis is the current cornerstone in public health policies directed towards the fights against cancer. In breast cancer and melanoma, the sentinel lymph node biopsy has been widely used for diagnoses of metastasis. The minor impact in patient of this technique compared with total nodes dissection and the accurate definition of therapeutic strategies have powered its spreading. The aim of this work was the development of radiolabeled dextran-mannose conjugates for diagnosis using the stable technetium core [ 99m Tc(CO)3] + . Cysteine, a trident ligand, was attached to the conjugates backbone, as a chelate for 99m Tc labeling. Radiolabeling conditions established for all products considered in this study showed high radiochemical purities (> 90%) and specific activities (>59,9 MBq/nmol) as well and high stability obtained through in vitro tests. The lymphatic node uptake increased significantly (4-folds) when mannose units were added to the conjugates compared with those without this monosaccharide. The radiolabeled cysteine-mannose-dextran conjugate with 30 kDa ( 99m Tc - DCM2) showed the best performance at different injected activities among the studied tracers. Concentrations of this radio complex higher than 1 M demonstrated an improvement of lymph node uptakes. Comparisons of 99m Tc - DCM2 performance with commercial radiopharmaceuticals in Brazil market for lymph node detection showed its upper profile. (author)

  9. A novel method for radiolabeling antigen-binding receptors of lymphocytes

    International Nuclear Information System (INIS)

    Choi, Y.S.; Lee, M.S.; Rosenspire, A.J.

    1983-01-01

    Antigen-binding receptor (ABR) molecules have been selectively radiolabeled and isolated from immunized chicken spleen cells. The specific radiolabeling of the receptors has been accomplished by utilizing a novel technique employing lactoperoxidase (LPO) covalently linked to antigen (Ag) for which human gammaglobulin was used. The cell surface ABRs were first bound to the Ag-LPO conjugates through specific recognition sites on the Ag portion of the conjugates. The bound LPO portions were then allowed to catalyze the radioiodination of the ABRs. After radiolabeling, cells were solubilized with detergents, ABRs still bound to Ag-LPO conjugates were directly isolated from the lysates via immunoaffinity chromatography utilizing an immunoaffinity reagent directed toward the antigen portion of the ABR-Ag-LPO complex. The radioactive materials were then analyzed via SDS-PAGE under reducing conditions. Most of the specifically-labeled and isolated materials were immunoglobulin (Ig). Both the membrane-bound form of the heavy chain as well as the secreted form were detected, along with the light chain. An additional polypeptide was also selectively labeled and isolated along with the Ig. This may be a molecule closely associated with the membrane immunoglobulin on the B-cell surface. (author)

  10. Radiolabeled cholesteryl ethers: A need to analyze for biological stability before use.

    Science.gov (United States)

    Manual Kollareth, Denny Joseph; Chang, Chuchun L; Hansen, Inge H; Deckelbaum, Richard J

    2018-03-01

    Radiolabeled cholesteryl ethers are widely used as non-metabolizable tracers for lipoproteins and lipid emulsions in a variety of in vitro and in vivo experiments. Since cholesteryl ethers do not leave cells after uptake and are not hydrolyzed by mammalian cellular enzymes, these compounds can act as markers for cumulative cell uptakes of labeled particles. We have employed [ 3 H]cholesteryl oleoyl ether to study the uptake and distribution of triglyceride-rich emulsion particles on animal models. However, questionable unexpected results compelled us to analyze the stability of these ethers. We tested the stability of two commercially available radiolabeled cholesteryl ethers - [ 3 H]cholesteryl oleoyl ether and [ 3 H]cholesteryl hexadecyl ether from different suppliers, employing in vitro , in vivo and chemical model systems. Our results show that, among the two cholesteryl ethers tested, one ether was hydrolyzed to free cholesterol in vitro , in vivo and chemically under alkaline hydrolyzing agent. Free cholesterol, unlike cholesteryl ether, can then re-enter the circulation leading to confounding results. The other ether was not hydrolyzed to free cholesterol and remained as a stable ether. Hence, radiolabeled cholesteryl ethers should be analyzed for biological stability before utilizing them for in vitro or in vivo experiments.

  11. Radiolabeled cholesteryl ethers: A need to analyze for biological stability before use

    Directory of Open Access Journals (Sweden)

    Denny Joseph Manual Kollareth

    2018-03-01

    Full Text Available Radiolabeled cholesteryl ethers are widely used as non-metabolizable tracers for lipoproteins and lipid emulsions in a variety of in vitro and in vivo experiments. Since cholesteryl ethers do not leave cells after uptake and are not hydrolyzed by mammalian cellular enzymes, these compounds can act as markers for cumulative cell uptakes of labeled particles. We have employed [3H]cholesteryl oleoyl ether to study the uptake and distribution of triglyceride-rich emulsion particles on animal models. However, questionable unexpected results compelled us to analyze the stability of these ethers. We tested the stability of two commercially available radiolabeled cholesteryl ethers - [3H]cholesteryl oleoyl ether and [3H]cholesteryl hexadecyl ether from different suppliers, employing in vitro, in vivo and chemical model systems. Our results show that, among the two cholesteryl ethers tested, one ether was hydrolyzed to free cholesterol in vitro, in vivo and chemically under alkaline hydrolyzing agent. Free cholesterol, unlike cholesteryl ether, can then re-enter the circulation leading to confounding results. The other ether was not hydrolyzed to free cholesterol and remained as a stable ether. Hence, radiolabeled cholesteryl ethers should be analyzed for biological stability before utilizing them for in vitro or in vivo experiments. Keywords: Cholesteryl ether, J774 A2 macrophages, Soy oil emulsion, Thin layer chromatography, triDHA emulsion

  12. Potential of 57Ni/57Co generator system for radiolabelling proteins for imaging

    International Nuclear Information System (INIS)

    Du, T.; Smith, S.V.; Baker, T.

    1998-01-01

    Full text: There is increasing interest in the use of inert metal complexes for radiolabelling proteins. The present study involves an investigation into the use to the parent/daughter system 57 Ni/ 57 Co for PET and SPECT imaging. In order to assess the potential of the system for such applications it is important to examine whether the ligand chosen complexes with both 57 Ni and 57 Co. A selection of ligands with varying number of donor groups and open-chain and macrocyclic ligands were chosen; ethylenediaminetetraacetic acid (EDTA), diethylenetriaminepentaacetic acid (DTPA), 1,4,8,11 - tetraazocyclotetradecane-1 4,8,11-tetraacetic acid (TETA) and diaminohydroxyaryl - diethylenetriaminepentaacetic acid, (DAHA-EDTA). Complexation behaviour over a range of pH and temperatures was investigated. Results show that the ligands have strong complexation for 57 Ni however once 57 Ni decayed to 57 Co evidence ol chemical instability was noted. The DAHA-EDTA ligand (developed in house) was observed to be the most stable under conditions studied. lt was selected for use in radiolabelling B72.3 antibody and preliminary radiolabelling conditions were established

  13. Radiolabeling small RNA with technetium-99m for visualizing cellular delivery and mouse biodistribution

    International Nuclear Information System (INIS)

    Liu Ning; Ding Hongliu; Vanderheyden, Jean-Luc; Zhu Zhihong; Zhang Yumin

    2007-01-01

    To develop a noninvasive direct method for the in vivo tracking of small interfering RNA (siRNA) used in RNA interference, two 18-nucleotide oligoribonucleotides were radiolabeled with technetium-99m ( 99m Tc-RNA). The ability of 99m Tc-RNA to track delivery was tested in cultured cells and living mice. The cellular delivery of 99m Tc-RNAs could be quantified by gamma counting and could be visualized by microautoradiography. Radiolabeled RNAs can be efficiently delivered into cells by reaching up to 3x10 5 molecules of small RNAs per cell. Moreover, RNAs were internalized with homogeneous distribution throughout the cytoplasm and nucleus. In tumor-bearing mice, whole-body images and biodistribution studies showed that 99m Tc-RNAs were delivered to almost all tissues after intravenous injection. The imaging of living animals allowed noninvasive and longitudinal monitoring of the in vivo delivery of these small RNAs. In conclusion, using 99m Tc radiolabeling, the delivery of small RNAs could be measured quantitatively in cultured cells and could be noninvasively visualized in living animals using a gamma camera. The results of this study could open up a new approach for measuring the in vivo delivery of small RNAs that might further facilitate the development of siRNAs as targeted therapies

  14. Selective suppression of antibody production with the aid of radiolabelled birch pollen allergen

    International Nuclear Information System (INIS)

    Filipp, G.; Biro, G.; Hartung, W.D.; Lehmann, G.

    1981-01-01

    In accordance with the clonal selection theory we intended to prevent the development of artificially induced birch pollen allergy in rabbits with the aid of of the radiolabelled pollen allergen (75-1000 μCi 125 I-pollen/animal) intravenously administered prior to pollen sensitization. The birch pollen allergen, in accordance with Burnet's working hypothesis, reacts only with a genetically determining B cell subpopulation. The fixation of the radiolabelled birch pollen allergen to the receptors of the competent B cell clone causes the lesion of the latter. Compared with the control group, this group of rabbits showed an extensive suppression of anaphylactic reagin-like PCA-antibodies, and haemagglutinating antibodies in the blood as well as in nasal secretion. In addition, we tried to influence the already ongoing synthesis of the antibodies with the aid of a subsequent intravenously administered radiolabelled birch pollen allergen (750-1000μCi 125 I-pollen/animal). An intensive suppression of the synthesis of antibodies could also be proved in this case. The simultaneous immunization of the control rabbits with birch pollen and egg albumin resulted in the production of antibodies against both antigens, as expected. The hot-labelled birch pollen antigen intravenously injected before or after immunization with egg albumin and birch pollen led selectively to suppression of anti-birch-pollen PCA antibodies. The synthesis of anti-egg albumin PCA antibodies was unaffected. (author)

  15. 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.).

  16. 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.

  17. Radiolabeling and animal experimental studies of anti-breast cancer McAb 6C6 and mouse-human chimeric antibody 6C6CHI

    International Nuclear Information System (INIS)

    Yang Zhi; Hu Xiaoqian; Li Erqiu

    2003-01-01

    The aim of this work is to study bio-distribution and tumor absorption of anti breast cancer monoclonal antibody 6C6 and its chimeric antibody 6C6-CHI. The modified Schwartz method was employed to label 6C6 and 6C6CHI with 99 Tc m . The labeled antibody was injected to mouse via tail vein and the blood clearance and whole body clearance were observed. Nude mice bearing breast cancer MCF7 were injected with 99 Tc m -labeled antibody and the bio-distribution was studied and imaged with γ-ray camera. The yield of the two labeled antibodies was more than 90% and their immunoactivities were more than 80%. The whole body eliminated half-time of 99 Tc m -6C6 was 4.1h, and the half-times in blood were T α =0.55h and T β =12.42h respectively. The whole body half-time of 99 Tc m -6C6CHI was 4.28h and the half-times in blood were T α =0.98h and T β =12.42h respectively. The bio-distribution of nude mice bearing breast cancer MCF7 cells was as follows: the ID%/g of tumor and blood was (7.42±0.85) and (5.67±1.44) respectively at 23h after injection of 99 Tc m -6C6. The T/NT (tumor to non tumor) ratios were all more than 1.0 except kidney and the ID%/g of tumor and blood was (4.23±0.64) and (6.97±0.23) respectively at 23 h after injection of 99 Tc m -6C6CHI. The T/NT (tumor to non tumor) ratios were all more than 1.0 except blood and kidney. The γ imaging results showed that the tumor was imaged clearly at 24h after injection of radiolabeled antibodies and the other organs did not concentrate the antibodies except kidney. Anti-breast cancer monoclonal antibody 6C6 can be well located in tumor. Although ID%/g of tumor of the chimeric antibody 6C6CHI was slightly lower than that of 6C6 antibody, and ID%/g of blood was higher than that of 6C6, the tumor imaging of 6C6-CHI was also clear

  18. Homeostatic T Cell Expansion to Induce Anti-Tumor Autoimmunity in Breast Cancer

    National Research Council Canada - National Science Library

    Baccala, Roberto

    2007-01-01

    ... that (a) homeostatic T-cell proliferation consistently elicits anti-tumor responses; (b) irradiation is more effective than Tcell depletion by antibodies in inducing anti-tumor responses mediated by homeostatic T-cell proliferation...

  19. Hydroxyurea derivatives of irofulven with improved antitumor efficacy.

    Science.gov (United States)

    Staake, Michael D; Kashinatham, Alisala; McMorris, Trevor C; Estes, Leita A; Kelner, Michael J

    2016-04-01

    Irofulven is a semi-synthetic derivative of Illudin S, a toxic sesquiterpene isolated from the mushroom Omphalotus illudens. Irofulven has displayed significant antitumor activity in various clinical trials but displayed a limited therapeutic index. A new derivative of irofulven was prepared by reacting hydroxyurea with irofulven under acidic conditions. Acetylation of this new compound with acetic anhydride produced a second derivative. Both of these new derivatives displayed significant antitumor activity in vitro and in vivo comparable to or exceeding that of irofulven. Copyright © 2016 Elsevier Ltd. All rights reserved.

  20. Modification of carcinogenic and antitumor radiation effects (biomedical aspects)

    International Nuclear Information System (INIS)

    Vilenchik, M.M.

    1985-01-01

    In the book the data on modification of carcinogenic radiation effects by physiologicaly active compounds (caffeine, hormones, promoters and others) as well as on potentiation of antitumor radiation effects by means of hyperthermia are systematized. It is shown that as a basis of synergetic (superadditive) carcinogenic or antitumor radiation effects combined with other factor can be the inhibiting effects of the latter on the reparation process of radiation-induced DNA injuries. The results of experimental investigations and the data on quantitative analysis can be used as a theoretical basis for improvement of the ways and means of the prophylaxis of tumor diseases as well as for increasing the efficiency of radiotherapy

  1. An Update on Antitumor Activity of Naturally Occurring Chalcones

    Directory of Open Access Journals (Sweden)

    En-Hui Zhang

    2013-01-01

    Full Text Available Chalcones, which have characteristic 1,3-diaryl-2-propen-1-one skeleton, are mainly produced in roots, rhizomes, heartwood, leaves, and seeds of genera Angelica, Sophora, Glycyrrhiza, Humulus, Scutellaria, Parartocarpus, Ficus, Dorstenia, Morus, Artocarpus, and so forth. They have become of interest in the research and development of natural antitumor agents over the past decades due to their broad range of mechanisms including anti-initiation, induction of apoptosis, antiproliferation, antimetastasis, antiangiogenesis, and so forth. This review summarizes the studies on the antitumor activity of naturally occurring chalcones and their underlying mechanisms in detail during the past decades.

  2. Dissociation of alloantigen recognition from self major histocompatibility complex-restricted recognition of cytolytic T lymphocytes by monoclonal antireceptor antibodies

    International Nuclear Information System (INIS)

    Kanagawa, O.; Nagasawa, R.

    1987-01-01

    Two monoclonal antibodies (mAb) directed to the dual reactive cytolytic T lymphocyte clone OH8 (D/sup b/T H-Y and H-2/sup d/) were established. Analysis by cell surface staining and immunoprecipitation of radiolabeled surface molecules of OH8 followed by sodium dodecyl sulfate-polyacrylamide gel electrophoresis reveled that both mAb recognized an identical heterodimeric, clonotypic structure on OH8 cells, i.e., T cell receptor. However, although the MR3-2 mAb inhibited the lysis of either D/sup b/ + H-Y or H-2/sup d/ targets by OH8, the MR3-6 mAb inhibited the lysis of H-2/sup d/ target cells, but not that of D/sup b/ + H-Y target cells. Modulation of T cell receptor by either MR3-2 or MR3-6 mAb rendered the OH8 cytolytic T lyrphocyte incapable of killing both D/sup b/ + H-Y and H-2/sup d/ target cells. These finding suggest that different epitopes of OH8 T cell receptor were involved for the recognition of self + antigen and alloantigen

  3. Demonstration of monoclonal anti-carcinoembryonic antigen (CEA) antibody internalization by electron microscopy, western blotting and radioimmunoassay.

    Science.gov (United States)

    Tsaltas, G; Ford, C H; Gallant, M

    1992-01-01

    One of the important factors affecting the action of monoclonal antibodies (Mabs) or immunoconjugates on tumour sites depends on whether the Mab is internalized by the cancer cells in question. The underexplored subject of internalization is discussed in this paper, and a number of in vitro techniques for investigating internalization are evaluated, using a model which consists of a well characterized anti-carcinoembryonic antigen (anti-CEA) Mab and a number of CEA expressing human cancer cell lines. Employing two alternative radiolabeling assays, evidence for internalization of the anti-CEA Mab by a CEA-positive colorectal cancer cell line (LS174T) was obtained throughout the time intervals examined (5 min to 150 min). Electronmicroscopy employing horseradish-peroxidase labeled anti-CEA Mab and control antibody permitted direct visualization of anti-CEA Mab-related staining in intracellular compartments of a high CEA-expressor human colorectal cell line (SKCO1). Finally Western blots of samples derived from cytosolic and membrane components of solubilized cells from lung and colonic cancer cell lines provided evidence for internalized anti-CEA Mab throughout seven half hour intervals, starting at 5 minutes. Internalized anti-CEA was detected in all CEA expressing cell lines (LS174T, SKCO1, BENN) but not in the case of a very low CEA expressor line (COLO 320).

  4. The in vivo fate of a 211At labelled monoclonal antibody with known specificity in a murine system

    International Nuclear Information System (INIS)

    Vaughan, A.T.M.; Bateman, W.J.; Fisher, D.R.

    1982-01-01

    A monoclonal antibody reactive against the human transferrin receptor has been labelled with the alpha and X ray emitting isotope Astatine 211. The labelling procedure does not affect the ability of the product to bind to the transferrin receptor on the human leukemic cell line HL60. Using a direct binding assay, 211 At labelled antibody can be specifically inhibited from binding to its target cells by excess unlabelled antibody. Furthermore, the binding inhibition demonstrated in this system correlates to enhanced clonogenic survival of these cells, indicating that very few atoms of 211 At/cell are required for cell death. Data obtained from labelled antibody injected into mice show that the labelled product in serum retains the ability to bind to HL60 cells in vitro, although tissue distributions of the injected activity implies that some of the radiolabel is lost from the protein. Despite this loss of label, preliminary experiments on the localization of labelled antibody to HL60 cells growing s/c in nude mice show that tumor tissue has a higher specific activity than all other tissues, other than blood, after 12 hours. This suggests that further work on the nature of label degradation in vivo is warranted in the context of potential therapeutic and diagnostic studies

  5. The study of conjugation of anti-CD20 monoclonal antibody for labeling with metallic or lanthanides radionuclides

    International Nuclear Information System (INIS)

    Akanji, Akinkunmi Ganiyu

    2012-01-01

    Lymphomas are malignancies or cancers that start from the malign transformation of a lymphocyte in the lymphatic system. Generally, lymphomas start from the lymph nodes or from the agglomeration of the lymphatic tissues, organs like stomach, intestines, in some cases it can involve the bone marrow and the blood, it can also disseminate to other organs. Lymphomas are divided in two major categories: Hodgkin lymphoma and non-Hodgkin lymphoma (NHL). Patient with NHL are generally treated with radiotherapy alone or combined with immunotherapy using monoclonal antibody rituximab (MabThera®). Currently, monoclonal antibodies (Acm) conjugated with bifunctional chelate agents and radiolabeled with metallic or lanthanides radionuclides are a treatment reality for patients with NHL by the principle of radioimmunotherapy (RIT). This study focused on the conditions of conjugation of Acm rituximab (MabThera®) with bifunctional chelating agents DOTA and DTPA. Various parameters were studied: method of Acm purification, conditions of Acm conjugation, the method for determination of number of chelate agent coupled to the Acm, method for purification of the conjugated antibody Acm, conditions of labeling of the conjugated antibody with lutetium-177, method of purification of the radiolabeled immuno conjugate, method of radiochemical purity (RP), specific binding in vitro Raji cells (Human Burkitt) and biological distribution performed in normal Balb-c mouse. The three methodologies employed in pre-purification of Acm (dialysis, size exclusion chromatograph and dial filtration) demonstrated to be efficient; they provided sample recovery exceeding 90%. However, the methodology of dial filtration presents minimal sample loss, and gave the final recovery of the sample in micro liters; thereby facilitating sample use in subsequent experiments. Numbers of chelators attached to the Acm molecule was proportional to the molar ratio studied. When we evaluated the influence of different

  6. Approaches in the design of 99mTc based peptide radiolabelling for tumour targeting

    International Nuclear Information System (INIS)

    Yokoyama, A.; Horiuchi, K.; Arano, Y.

    2001-01-01

    One of the major drawbacks in diagnostic and/or therapeutic uses of peptides radiolabelled with radiometals via bifunctional chelating agents (BCA) is their accumulation in excretory organs such as liver or kidney. Thus, the aim of the project is centred in the search for chemical and radiochemical approaches to reduce radioactivity accumulated in excretory organs while preserving the in vivo receptor binding affinity of the peptide. During the first stage a suitable procedure using the F-moc-chemistry (solid phase) was developed and synthesis of DTPA-D-Phen1-Octreotide and DTPA-L-Phen1-Octreotide was carried out. During the synthesis, the need to improve the yield demanded the synthesis of a DTPA derivative holding only one reactive carboxylic group to avoid side intermolecular reaction. The availability of both isomeric conjugated octreotide led to their radiolabelling with 111 In. Their metabolic studies in animals indicated that the degradation rate of the peptide containing the natural aminoacid, 111 In DTPA-L-Phen1-Octreotide, was slightly higher than the corresponding D-aminoacid derivative, as expected. Stability of the peptide during radiolabelling with 99m Tc was then studied, requiring the use of variable agents such as ascorbic acid, dithionite and stannous ion. The selected peptide, RC-160, was provided by the IAEA and, as reference compounds, corresponding iodinated and radioiodinated peptides were synthesized. Demonstration of the stability of the peptide was carried out using disodium 2-nitro-5-thiosulfobenzoate (NTBS) and the lack of Bunte salt formation served as an indication of the stability of the disulfide bond under various mild conditions required for the future radiolabelling with 99m Tc. The knowledge gained served in moving to the next stage of 99m Tc radiolabelling using HYNIC as the BCA and tricine as co-ligands. The biodistribution studies demonstrated great accumulation on excretory organs. This led us to look for a model protein

  7. The anti-tumor effect and biological activities of the extract JMM6 ...

    African Journals Online (AJOL)

    Juglans mandshurica Maxim is a traditional herbal medicines in China, and its anti-tumor bioactivities are of research interest. Bioassay-guided fractionation method was employed to isolate anti-tumor compounds from the stem barks of the Juglans mandshurica Maxim. The anti-tumor effect and biological activities of the ...

  8. Antitumor Properties of Modified Detonation Nanodiamonds and Sorbed Doxorubicin on the Model of Ehrlich Ascites Carcinoma.

    Science.gov (United States)

    Medvedeva, N N; Zhukov, E L; Inzhevatkin, E V; Bezzabotnov, V E

    2016-01-01

    We studied antitumor properties of modified detonation nanodiamonds loaded with doxorubicin on in vivo model of Ehrlich ascites carcinoma. The type of tumor development and morphological characteristics of the liver, kidneys, and spleen were evaluated in experimental animals. Modified nanodiamonds injected intraperitoneally produced no antitumor effect on Ehrlich carcinoma. However, doxorubicin did not lose antitumor activity after sorption on modified nanodiamonds.

  9. 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.

  10. 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.

  11. Nanobodies and Nanobody-Based Human Heavy Chain Antibodies As Antitumor Therapeutics

    Directory of Open Access Journals (Sweden)

    Peter Bannas

    2017-11-01

    Full Text Available Monoclonal antibodies have revolutionized cancer therapy. However, delivery to tumor cells in vivo is hampered by the large size (150 kDa of conventional antibodies. The minimal target recognition module of a conventional antibody is composed of two non-covalently associated variable domains (VH and VL. The proper orientation of these domains is mediated by their hydrophobic interface and is stabilized by their linkage to disulfide-linked constant domains (CH1 and CL. VH and VL domains can be fused via a genetic linker into a single-chain variable fragment (scFv. scFv modules in turn can be fused to one another, e.g., to generate a bispecific T-cell engager, or they can be fused in various orientations to antibody hinge and Fc domains to generate bi- and multispecific antibodies. However, the inherent hydrophobic interaction of VH and VL domains limits the stability and solubility of engineered antibodies, often causing aggregation and/or mispairing of V-domains. Nanobodies (15 kDa and nanobody-based human heavy chain antibodies (75 kDa can overcome these limitations. Camelids naturally produce antibodies composed only of heavy chains in which the target recognition module is composed of a single variable domain (VHH or Nb. Advantageous features of nanobodies include their small size, high solubility, high stability, and excellent tissue penetration in vivo. Nanobodies can readily be linked genetically to Fc-domains, other nanobodies, peptide tags, or toxins and can be conjugated chemically at a specific site to drugs, radionuclides, photosensitizers, and nanoparticles. These properties make them particularly suited for specific and efficient targeting of tumors in vivo. Chimeric nanobody-heavy chain antibodies combine advantageous features of nanobodies and human Fc domains in about half the size of a conventional antibody. In this review, we discuss recent developments and perspectives for applications of nanobodies and nanobody

  12. Nanobodies and Nanobody-Based Human Heavy Chain Antibodies As Antitumor Therapeutics.

    Science.gov (United States)

    Bannas, Peter; Hambach, Julia; Koch-Nolte, Friedrich

    2017-01-01

    Monoclonal antibodies have revolutionized cancer therapy. However, delivery to tumor cells in vivo is hampered by the large size (150 kDa) of conventional antibodies. The minimal target recognition module of a conventional antibody is composed of two non-covalently associated variable domains (VH and VL). The proper orientation of these domains is mediated by their hydrophobic interface and is stabilized by their linkage to disulfide-linked constant domains (CH1 and CL). VH and VL domains can be fused via a genetic linker into a single-chain variable fragment (scFv). scFv modules in turn can be fused to one another, e.g., to generate a bispecific T-cell engager, or they can be fused in various orientations to antibody hinge and Fc domains to generate bi- and multispecific antibodies. However, the inherent hydrophobic interaction of VH and VL domains limits the stability and solubility of engineered antibodies, often causing aggregation and/or mispairing of V-domains. Nanobodies (15 kDa) and nanobody-based human heavy chain antibodies (75 kDa) can overcome these limitations. Camelids naturally produce antibodies composed only of heavy chains in which the target recognition module is composed of a single variable domain (VHH or Nb). Advantageous features of nanobodies include their small size, high solubility, high stability, and excellent tissue penetration in vivo . Nanobodies can readily be linked genetically to Fc-domains, other nanobodies, peptide tags, or toxins and can be conjugated chemically at a specific site to drugs, radionuclides, photosensitizers, and nanoparticles. These properties make them particularly suited for specific and efficient targeting of tumors in vivo . Chimeric nanobody-heavy chain antibodies combine advantageous features of nanobodies and human Fc domains in about half the size of a conventional antibody. In this review, we discuss recent developments and perspectives for applications of nanobodies and nanobody-based human heavy

  13. Biochemical and histological evidences for the antitumor potential of ...

    African Journals Online (AJOL)

    Biochemical and histological evidences for the antitumor potential of Teucrium Oliverianum and Rhazya stricta in chemically-induced hepatocellular carcinoma. ... Photomicrograph of liver tissue sections of rats in HCC revealed hepatic parenchyma with foci of anaplastic hepatocellular carcinoma as well as other foci of ...

  14. Cisplatin carbonato complexes. Implications for uptake, antitumor properties, and toxicity.

    Science.gov (United States)

    Centerwall, Corey R; Goodisman, Jerry; Kerwood, Deborah J; Dabrowiak, James C

    2005-09-21

    The reaction of aquated cisplatin with carbonate which is present in culture media and blood is described. The first formed complex is a monochloro monocarbonato species, which upon continued exposure to carbonate slowly forms a biscarbonato complex. The formation of carbonato species under conditions that simulate therapy may have important implications for uptake, antitumor properties, and toxicity of cisplatin.

  15. Juglans regia Hexane Extract Exerts Antitumor Effect, Apoptosis ...

    African Journals Online (AJOL)

    Original Research Article. Juglans regia Hexane Extract Exerts Antitumor Effect,. Apoptosis Induction and Cell Circle Arrest in Prostate. Cancer Cells In vitro. Wei Li1, De-Yuan Li2*, ... composition of walnut is juglone (5-hydroxy-1, 4- naphthoquinone), the .... extract was confirmed by studying apoptotic body formation using ...

  16. Anti-tumor activity of polysaccharides extracted from Senecio ...

    African Journals Online (AJOL)

    *, Bao Zhang, Mingming Han, Xin Jin, Liyuan Sun and Tao Li. Department of ..... Yang J, Li X, Xue Y, Wang N, Liu W. Anti-hepatoma activity and mechanism of corn ... Peng W, Wu JG, Jiang YB, Liu YJ, Sun T, Wu N, Wu CJ. Antitumor activity of ...

  17. Indicine-N-oxide: the antitumor principle of Heliotropium indicum.

    Science.gov (United States)

    Kugelman, M; Liu, W C; Axelrod, M; McBride, T J; Rao, K V

    1976-01-01

    Extracts of Heliotropium indicum Linn. (Boraginaceae) showed significant activity in several experimental tumor systems. The active principle is isolated and shown to be the N-oxide of the alkaloid, indicine, previously isolated from this plant. Supporting structural data and anti-tumor data are provided.

  18. Mechanisms of reduction of antitumor drug toxicity by liposome encapsulation

    Energy Technology Data Exchange (ETDEWEB)

    Rahman, Y. E.; Hanson, W. R.; Bharucha, J.; Ainsworth, E. J.; Jaroslow, B.

    1977-01-01

    The antitumor drug Actinomycin D is effective against the growth of some human solid tumors but its use is limited by its extreme toxicity. The development of a method of administering Act. D to reduce its systemic toxicity by incorporating the drug within liposomes reduced its toxicity but its tumoricidal activity was retained.

  19. Antitumor activity of doxorubicine-loaded nanoemulsion against ...

    African Journals Online (AJOL)

    Pharmacotherapy Group, Faculty of Pharmacy, University of Benin, Benin City, 300001 Nigeria. All rights ... Keywords: Doxorubicine, Anti-tumor activity, Mean survival time, Heart histology, Nanoemulsion, Lipid profile .... the standard kit methods using fully Automated ..... effects of this new formulation in human patients.

  20. Reprogramming Antitumor Immune Responses with microRNAs

    Science.gov (United States)

    2013-10-01

    disease, including cancer etiology (4) and the generation and inhibition of antitumor immune responses (5–9). Biologically active miRNAs bind to MREs...breast, colorectal, lung, pancreatic , and thyroid carcinomas and in liquid tumors including lymphomas and some acute myeloid leukemias (9, 35). The...immunity [9], underscoring the potential of targeting this major microenvironmental compartment. Accumulating evidence suggests that chronic