WorldWideScience

Sample records for radiolabeling humanized anti-cea

  1. Uptake of radiolabeled anti-CEA antibodies in human colorectal primary tumors as a function of tumor mass

    International Nuclear Information System (INIS)

    Williams, L.E.; Bares, R.B.; Buell, U.; Fass, J.; Schumpelick, V.; Hauptmann, S.

    1993-01-01

    An inverse correlation has been demonstrated between tumor uptake (u, in units of % injected dose/kg) of monoclonal antibody (Mab) and tumor mass (m, in units of g) for colorectal carcinoma in a series of 19 consecutive patients. The correlation (ρ=-0.510), developed using surgical samples was of the form u=ab b and was significant at the 2% level of confidence. All tumors were positive for carcinoembryonic antigen (CEA) and the radiopharmaceutical was in iodine-131 labeled anti-CEA Mab. Such correlations have been predicted earlier from murine and rat tumor uptake data. The slope parameter (b) was -0.362, a number consistent with the previous value (-0.382) found in anti-CEA experiments in mice bearing human xenograft LS174T tumors. (orig.)

  2. Fluorescently labeled chimeric anti-CEA antibody improves detection and resection of human colon cancer in a patient-derived orthotopic xenograft (PDOX) nude mouse model.

    Science.gov (United States)

    Metildi, Cristina A; Kaushal, Sharmeela; Luiken, George A; Talamini, Mark A; Hoffman, Robert M; Bouvet, Michael

    2014-04-01

    The aim of this study was to evaluate a new fluorescently labeled chimeric anti-CEA antibody for improved detection and resection of colon cancer. Frozen tumor and normal human tissue samples were stained with chimeric and mouse antibody-fluorophore conjugates for comparison. Mice with patient-derived orthotopic xenografts (PDOX) of colon cancer underwent fluorescence-guided surgery (FGS) or bright-light surgery (BLS) 24 hr after tail vein injection of fluorophore-conjugated chimeric anti-CEA antibody. Resection completeness was assessed using postoperative images. Mice were followed for 6 months for recurrence. The fluorophore conjugation efficiency (dye/mole ratio) improved from 3-4 to >5.5 with the chimeric CEA antibody compared to mouse anti-CEA antibody. CEA-expressing tumors labeled with chimeric CEA antibody provided a brighter fluorescence signal on frozen human tumor tissues (P = 0.046) and demonstrated consistently lower fluorescence signals in normal human tissues compared to mouse antibody. Chimeric CEA antibody accurately labeled PDOX colon cancer in nude mice, enabling improved detection of tumor margins for more effective FGS. The R0 resection rate increased from 86% to 96% with FGS compared to BLS. Improved conjugating efficiency and labeling with chimeric fluorophore-conjugated antibody resulted in better detection and resection of human colon cancer in an orthotopic mouse model. © 2013 Wiley Periodicals, Inc.

  3. Localization of radiolabeled anti-CEA antibody in subcutaneous and intrahepatic colorectal xenografts: influence of tumor size and location within host organ on antibody uptake

    Energy Technology Data Exchange (ETDEWEB)

    Dearling, Jason L.J. [Cancer Research UK Targeting and Imaging Group, Research Department of Oncology, UCL Cancer Institute, Paul O' Gorman Building, University College London, London WC1E 6BT (United Kingdom)], E-mail: j.dearling@hotmail.com; Flynn, Aiden A.; Qureshi, Uzma [Cancer Research UK Targeting and Imaging Group, Research Department of Oncology, UCL Cancer Institute, Paul O' Gorman Building, University College London, London WC1E 6BT (United Kingdom); Whiting, Stephen [Department of Clinical Biochemistry, Royal Free and University College Medical School, UCL, Royal Free Campus, London NW3 2PF (United Kingdom); Boxer, Geoffrey M.; Green, Alan; Begent, Richard H.J.; Pedley, R. Barbara [Cancer Research UK Targeting and Imaging Group, Research Department of Oncology, UCL Cancer Institute, Paul O' Gorman Building, University College London, London WC1E 6BT (United Kingdom)

    2009-11-15

    Introduction: Radioimmunotherapy (RIT) has been shown to be more effective against solid tumor micrometastases, possibly due to an inverse relationship between tumor size and radiolabeled antibody uptake. In this study, the accretion of radiolabeled antibody in intrahepatic micrometastases in an experimental model was investigated using quantitative digital autoradiography, enabling the analysis of antibody uptake in microscopic tumors. Methods: Mice bearing subcutaneous or intrahepatic metastatic models of LS174T colorectal cancer were injected with radiolabeled anti-carcinoembryonic antigen antibody ([{sup 125}I]A5B7). Tissues were taken to investigate distribution of radionuclide and tumor uptake. In a therapy study, mice bearing intrahepatic metastatic tumors were injected with [{sup 131}I]A5B7. Results: Subcutaneous tumors and large metastatic deposits had similar uptake (e.g., {approx}15%ID/g at 24 h). Small metastatic deposits had higher uptake (e.g., {approx}80%ID/g at 24 h) and prolonged retention at later time points. Small deposit uptake was significantly reduced by accompanying large deposits in the same liver. RIT resulted in increased survival time (untreated mean survival of 21.6{+-}12.9 vs. treated mean survival of 39.1{+-}30.8 days), but there was a large range of response within groups, presumably due to variation in pattern and extent of tumor as observed in the biodistribution study. Liver function tests and body weight did not change with tumor growth or therapy response, strongly supporting the use of in vivo imaging in metastatic tumor therapy studies. Conclusions: Radioimmunodetection and therapy might be greatly influenced by the size and distribution of intrahepatic tumor deposits.

  4. Localization of radiolabeled anti-CEA antibody in subcutaneous and intrahepatic colorectal xenografts: influence of tumor size and location within host organ on antibody uptake

    International Nuclear Information System (INIS)

    Dearling, Jason L.J.; Flynn, Aiden A.; Qureshi, Uzma; Whiting, Stephen; Boxer, Geoffrey M.; Green, Alan; Begent, Richard H.J.; Pedley, R. Barbara

    2009-01-01

    Introduction: Radioimmunotherapy (RIT) has been shown to be more effective against solid tumor micrometastases, possibly due to an inverse relationship between tumor size and radiolabeled antibody uptake. In this study, the accretion of radiolabeled antibody in intrahepatic micrometastases in an experimental model was investigated using quantitative digital autoradiography, enabling the analysis of antibody uptake in microscopic tumors. Methods: Mice bearing subcutaneous or intrahepatic metastatic models of LS174T colorectal cancer were injected with radiolabeled anti-carcinoembryonic antigen antibody ([ 125 I]A5B7). Tissues were taken to investigate distribution of radionuclide and tumor uptake. In a therapy study, mice bearing intrahepatic metastatic tumors were injected with [ 131 I]A5B7. Results: Subcutaneous tumors and large metastatic deposits had similar uptake (e.g., ∼15%ID/g at 24 h). Small metastatic deposits had higher uptake (e.g., ∼80%ID/g at 24 h) and prolonged retention at later time points. Small deposit uptake was significantly reduced by accompanying large deposits in the same liver. RIT resulted in increased survival time (untreated mean survival of 21.6±12.9 vs. treated mean survival of 39.1±30.8 days), but there was a large range of response within groups, presumably due to variation in pattern and extent of tumor as observed in the biodistribution study. Liver function tests and body weight did not change with tumor growth or therapy response, strongly supporting the use of in vivo imaging in metastatic tumor therapy studies. Conclusions: Radioimmunodetection and therapy might be greatly influenced by the size and distribution of intrahepatic tumor deposits.

  5. Preparation of one-vial reduced anti-CEA kit

    International Nuclear Information System (INIS)

    Hamada, Elena Setuko; Muramoto, Emiko; Shiraishi, Emilia Mayumi; Silva, Licia Maria Britto da; Martins, Heidi Pinto; Silva, Constanca Pagano Goncalves da

    1996-01-01

    A rapid and reliable instant reduced anti-CEA lyophilized kit for labelling with 99m Tc was developed. Each vial contains 0.5 mg of reduced anti-CEA, 40 μg of mendronate (MDP), 2.75 μg stannous fluoride (Sn F 2 ) and 15 μ g p-aminobenzoic acid (PABA). Labeling efficiency and stability were higher than 95% and were determined by instant paper chromatography. Biodistribution studies were performed in normal isogenic BALB/c mice at 4,6 and 24 hours after intravenous administration of the radiolabelled product. The maximum amount of activity was accumulated in the liver followed by intestines and kidneys. (author)

  6. Fluorescent humanized anti-CEA antibody specifically labels metastatic pancreatic cancer in a patient-derived orthotopic xenograft (PDOX) mouse model

    Science.gov (United States)

    Lwin, Thinzar M.; Miyake, Kentaro; Murakami, Takashi; DeLong, Jonathan C.; Yazaki, Paul J.; Shivley, John E.; Clary, Bryan; Hoffman, Robert M.; Bouvet, Michael

    2018-03-01

    Specific tumor targeting can result in selective labeling of cancer in vivo for surgical navigation. In the present study, we show that the use of an anti-CEA antibody conjugated to the near-infrared (NIR) fluorescent dye, IRDye800CW, can selectively target and label pancreatic cancer and its metastases in a clinically relevant patient derived xenograft mouse model.

  7. 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)

  8. A fundamental study of immunoscintigraphy with sup 131 I-labeled anti-CA 19-9 and anti-CEA monoclonal antibodies; Imaging of tumor-bearing mice by IMACIS-1 and cell ELISA with human tumor cells

    Energy Technology Data Exchange (ETDEWEB)

    Nogami, Toshihiko; Miura, Hiroshi; Ohmi, Shoichi; Kazahaya, Yasuhiro [CIS DIAGNOSTIC K.K., Chiba (Japan)

    1990-05-01

    A study was made on 2 types of {sup 131}I-labeled anti-CA 19-9 and anti-CEA mouse monoclonal antibodies (IMACIS-1) against human cancer related antigen as to their usefulness in radioimmunoimaging. Tumor-bearing nude mice were used for comparison. The transplanted tumors (SW948, COLO 201) were clearly visualized 48-72 hours after administration of IMACIS-1. Tumor/blood ratio 72 hours after administration: 8.69 in COLO 201 and 5.70 in SW948, showing ca. 10-15 times as high as those in PC-3 and HEp-2. IMACIS-1 therefore is considered useful in radioimmunoimaging of cancer. Analysis was made by in vitro cell ELISA. As a result, both of the cells specifically reacted with anti-CA 19-9 but not anti-CEA. (author).

  9. Use and limitations of radiolabelled anti-CEA antibodies and their fragments for photoscanning detection of human colorectal carcinomas

    Energy Technology Data Exchange (ETDEWEB)

    Mach, J P; Forni, M; Ritschard, J; Buchegger, F; Carrel, S; Widgren, S; Donath, A; Alberto, P [Lausanne Univ. (Switzerland)

    1980-08-01

    Fifty-three patients with histologically proven carcinoma were injected with highly purified (/sup 131/I)-labelled goat antibodies or fragments of antibodies against carcinoembryonic antigen (CEA). Each patient was tested by external photoscanning 4, 24, 36, 48h after injection. In 22 patients (16 of 38 injected with intact antibodies, 5 of 13 with F(ab')/sub 2/ fragments and 1 of 2 with Fab' fragments), an increased concentration of /sup 131/I radioactivity corresponding to the previously known tumor location was detected by photoscanning 36-48 h after injection. Blood pool and secreted radioactivity was determined in all patients by injecting 15 min after scanning, (sup(99m)Tc)-labeled normal serum albumin and free sup(99m)TcO/sub 4//sup -/. The computerized subtraction of sup(99m)Tc from /sup 131/I radioactivity enhanced the definition of tumor localization in the 22 positive patients. However, in spite of the computerized subtraction, interpretation of the scans remained doubtful for 12 patients and was entirely negative for 19 additional patients.

  10. Radioimmunoscintigraphy with I-131-labelled anti-CEA monclonal antibody in colorectal cancer patients

    International Nuclear Information System (INIS)

    Xie Tianhao

    1988-01-01

    Twenty three colorectal carcinoma and two benign polyposis patients with operatively and histologically proven were studied by radioimmunoscintigraphy, using anti-CEA monoclonal antibodies (C14-17 and C50) radiolabeled with I-131 . Computer assisted processing for the subtraction of Tc-99m background radioactivity was used to enhance the detection and localization of tumor which is visualized by immune scintigraphy. The size of tumor and the ratios of tumor to nontumor (T/NT) are two very important factors for the external immunoscintigraphy. The antibody uptake and retention in tumor are likely to depend on the degree of vascularity and diffusion into the viable tumor mass. Based upon the obtained results, the sensitivity of the method (true-poditive) was 91%, its specificity (true-negative) was 100%. This study thus indicates that radioimmunoscintigraphy of cancer with radioactive anti-CEA monoclonal antibody is very uaeful in the diagnoses of patients with CEA-containing neoplasms

  11. 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

  12. The biodistribution and pretargeting radioimmunoimaging of the fusion protein of anti-CEA single-chain antibody and core-streptavidin in human rectocolonic tumor bearing nude mice

    International Nuclear Information System (INIS)

    Yang Weidong; Li Biao; Zhu Chengmo; Jiang Xufeng; Feng Guowei; Wu Xiangpu

    2002-01-01

    Objective: To investigate the biodistribution and two-step pretargeting radioimmunoimaging of the fusion protein of anti-carcinoembryonic antigen (CEA) single-chain antibody (ScFv) and core-streptavidin in human rectocolonic tumor bearing nude mice. Methods: Before the injection of 153 Sm-biotin, the fusion protein of ScFv-core-streptavidin was pretargeted for 24 h (200 μg every nude mouse), 24 h later 153 Sm-biotin was injected. The uptake of radioactivity in tumor and normal tissues in 20 nude mice was measured at 1, 4, 8 and 24 h and the other 3 nude mice was scanned at 8 and 24 h after peritoneal injection of 153 Sm-biotin. Results: The tumor to blood ratio (tumor/blood) reached 0.49 , 1.21, 1.56 and 3.09 at 1, 4, 8 and 24 h respectively. Radioactivity concentration peaked at 8 h in tumor site and demonstrated a 'hot' area, with significant decreasing its background at 24 h. Conclusion: The fusion protein can elevate the tumor/blood ratio, shorten pretargeting and imaging process and also improve image quality

  13. In vitro and in vivo comparison of binding of 99m-Tc-labeled anti-CEA MAb F33-104 with 99m-Tc-labeled anti-CEA MAb BW431/26

    International Nuclear Information System (INIS)

    Watanabe, N.; Gunma Univ. School of Medicine; Oriuchi, N.; Inoue, T.; Sugiyama, S.; Kuroki, M.; Matsuoka, Y.; Tanada, S.; Murata, H.; Sasaki, Y.

    1999-01-01

    Aim: The purpose of this study was to assess the potential for radioimmunodetection (RAID) of murine anti-carcinoembryonic antigen (CEA) monoclonal antibody (MAb) F33-104 labeled with technetium-99m (99m-Tc) by a reduction-mediated labeling method. Methods: The binding capacity of 99m-Tc-labeled anti-CEA MAb F33-104 with CEA by means of in vitro procedures such as immunoradiometric assay and cell binding assay and the biodistribution of 99m-Tc-labeled anti-CEA MAb F33-104 in normal nude mice and nude mice bearing human colon adenocarcinoma LS180 tumor were investigated and compared with 99m-Tc-labeled anti-CEA MAb BW431/26. Results: The in vitro binding rate of 99m-Tc-labeled anti-CEA MAb F33-104 with CEA in solution and attached to the cell membrane was significantly higher than 99m-Tc-labeled anti-CEA MAb BW431/261 (31.4 ± 0.95% vs. 11.9 ± 0.55% at 100 ng/mL of soluble CEA, 83.5 ± 2.84% vs. 54.0 ± 2.54% at 10 7 of LS 180 cells). In vivo, accumulation of 99m-Tc-labeled anti-CEA MAb F33-104 was higher at 18 h postinjection than 99m-Tc-labeled anti-CEA MAb BW431/26 (20.1 ± 3.50% ID/g vs. 14.4 ± 3.30% ID/g). 99m-Tc-activity in the kidneys of nude mice bearing tumor was higher at 18 h postinjection than at 3 h (12.8 ± 2.10% ID/g vs. 8.01 ± 2.40% ID/g of 99m-Tc-labeled anti-CEA MAb F33-104, 10.7 ± 1.70% ID/g vs. 8.10 ± 1.75% ID/g of 99m-Tc-labeled anti-CEA MAb BW431/26). Conclusion: 99m-Tc-labeled anti-CEA MAb F33-104 is a potential novel agent for RAID of recurrent colorectal cancer. (orig.) [de

  14. 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

  15. 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

  16. Biodistribution and tumor imaging of an anti-CEA single-chain antibody-albumin fusion protein

    International Nuclear Information System (INIS)

    Yazaki, Paul J.; Kassa, Thewodros; Cheung, Chia-wei; Crow, Desiree M.; Sherman, Mark A.; Bading, James R.; Anderson, Anne-Line J.; Colcher, David; Raubitschek, Andrew

    2008-01-01

    Albumin fusion proteins have demonstrated the ability to prolong the in vivo half-life of small therapeutic proteins/peptides in the circulation and thereby potentially increase their therapeutic efficacy. To evaluate if this format can be employed for antibody-based imaging, an anticarcinoembryonic antigen (CEA) single-chain antibody(scFv)-albumin fusion protein was designed, expressed and radiolabeled for biodistribution and imaging studies in athymic mice bearing human colorectal carcinoma LS-174T xenografts. The [ 125 I]-T84.66 fusion protein demonstrated rapid tumor uptake of 12.3% injected dose per gram (ID/g) at 4 h that reached a plateau of 22.7% ID/g by 18 h. This was a dramatic increase in tumor uptake compared to 4.9% ID/g for the scFv alone. The radiometal [ 111 In]-labeled version resulted in higher tumor uptake, 37.2% ID/g at 18 h, which persisted at the tumor site with tumor: blood ratios reaching 18:1 and with normal tissues showing limited uptake. Based on these favorable imaging properties, a pilot [ 64 Cu]-positron emission tomography imaging study was performed with promising results. The anti-CEA T84.66 scFv-albumin fusion protein demonstrates highly specific tumor uptake that is comparable to cognate recombinant antibody fragments. The radiometal-labeled version, which shows lower normal tissue accumulation than these recombinant antibodies, provides a promising and novel platform for antibody-based imaging agents

  17. Radioiodination of monoclonal antibody intact anti-CEA

    International Nuclear Information System (INIS)

    Okada, H.; Souza, I.T.T.; Silva, C.P.G.

    1990-11-01

    The purpose of this study is to examine a convenient system that can be used to iodinate monoclonal antibodies which is rapid, simple, efficient and reproducible, and which can be accomplished in radiopharmaceutical laboratories. It is important to remember that antibodies are sensitive biochemicals, subject to losses of the activity that is essential to their mode of action, namely the ability to bind specific antigen. The advent of solid phase iodination agents has greatly expanded the range of gentle iodination techniques available for iodinating sensitive biological materials. The agent most widely used is the Iodogen (1,3,4,6 tetrachloro-3a-6a diphenylglycoluril) method. Anti-CEA 4C sub(11) IgG sub(2a,k) (prepared in the Ludwig Institute-Sao Paulo-Brazil ) is used as model to evaluate the Iodogen methodology. The miniature chromatographic system, also rapid, accurate, simple, efficient was elaborated to determine the labelling efficiency incorporation of iodine into immunoglobulin, and the radiochemical purity of sup(131)I-anti-CEA. (author)

  18. Immunoscintigraphy of metastases with radiolabelled human antibodies

    Energy Technology Data Exchange (ETDEWEB)

    Al-Azzawi, F.; Smith, J.; Stimson, W.H.

    1987-02-28

    It was concluded that Epstein-Barr virus transformation of committed lymphocytes offers great potential in the production of antitumour antibodies of human origin. An outline case report is presented where the human I/sup 131/ labelled antibody was used as a targeting agent to delineate the extent of secondary growth in the liver. (U.K.).

  19. Anti-CEA loaded maghemite nanoparticles as a theragnostic device for colorectal cancer

    Directory of Open Access Journals (Sweden)

    Campos da Paz M

    2012-10-01

    Full Text Available Mariana Campos da Paz,1 Maria de Fátima M Almeida Santos,1 Camila MB Santos,2 Sebastião W da Silva,2 Lincoln Bernardo de Souza,3 Emília CD Lima,3 Renata C Silva,1 Carolina M Lucci,1 Paulo César Morais,2 Ricardo B Azevedo,1 Zulmira GM Lacava11Instituto de Ciências Biológicas; 2Instituto de Física, Universidade de Brasília, Brasília, DF, Brazil; 3Instituto de Química, Universidade Federal de Goiás, Goiânia, GO, BrazilAbstract: Nanosized maghemite particles were synthesized, precoated (with dimercaptosuccinic acid and surface-functionalized with anticarcinoembryonic antigen (anti-CEA and successfully used to target cell lines expressing the CEA, characteristic of colorectal cancer (CRC cells. The as-developed nanosized material device, consisting of surface decorated maghemite nanoparticles suspended as a biocompatible magnetic fluid (MF sample, labeled MF-anti-CEA, was characterized and tested against two cell lines: a high-CEA expressing cell line (LS174T and a low-CEA expressing cell line (HCT116. Whereas X-ray diffraction was used to assess the average core size of the as-synthesized maghemite particles (average 8.3 nm in diameter, dynamic light scattering and electrophoretic mobility measurements were used to obtain the average hydrodynamic diameter (550 nm and the zeta-potential (−38 mV of the as-prepared and maghemite-based nanosized device, respectively. Additionally, surface-enhanced Raman spectroscopy (SERS was used to track the surface decoration of the nanosized maghemite particles from the very first precoating up to the attachment of the anti-CEA moiety. The Raman peak at 1655 cm−1, absent in the free anti-CEA spectrum, is the signature of the anti-CEA binding onto the precoated magnetic nanoparticles. Whereas MTT assay was used to confirm the low cell toxicity of the MF-anti-CEA device, ELISA and Prussian blue iron staining tests performed with both cell lines (LS174T and HCT116 confirm that the as-prepared MF-anti-CEA

  20. Iodine-131 labeled anti-CEA polyclonal antibody detection of gastrointestinal cancer

    International Nuclear Information System (INIS)

    Nabi, H.A.; Hinkle, G.H.; Olsen, J.O.; Haagensen, D.A.; Thurston, M.O.; Mojzisik, C.; Houchens, D.; Martin, E.W. Jr.

    1984-01-01

    To localize gastrointestinal tumor, 31 patients were injected with 1.7-2.1 mCi I-131 anti-CEA baboon polyclonal antibody. Whole body imaging at 48, 72, and occasionally 96 hrs was performed with a Signa Camera (Technicare) peaked at 364 keV with 20% window. Additional spot views were usually obtained. No subtraction methods were used. All patients had surgical and pathological confirmation of the nuclear medicine studies. Labeled antibody images were positive in 15 (8 recurrent or metastatic colorectal, 2 gastric, 1 pancreatic, 1 primary colon, and 1 breast metastatic to chest wall). In 1, antibody images were positive for metastatic deposits in para-aortic lymph nodes, but negative for primary rectal tumor. True negative images were observed in 6; false negative images in 9 (4 liver metastases, 2 rectal, 1 pancreatic, 1 mesenteric lymph node metastasis, 1 bone metastasis). In all cases, no correlation existed between preoperative CEA serum levels and imaging. I-131 labeled anti-CEA polyclonal antibody imaging proved highly efficient in detecting gastric cancer (2/2) and moderately efficient in detecting recurrent colorectal cancer (8/15). On the other hand, the I-131 labeled polyclonal anti-CEA antibody imaging was of limited value in detecting colon cancer (1/9), pancreatic cancer (1/4) and metastatic liver disease

  1. Anti-CEA monoclonal antibody in the diagnosis of colorectal, lung and ovarian carcinoma

    International Nuclear Information System (INIS)

    Jiang, N.; Lu, B.; Lu, X.; Sha, X.; Yue, D.

    2000-01-01

    This study evaluated the diagnostic value of radioimmnoimaging (RII) with 99 Tc labeled monoclonal antibody C50, raised originally against carcinoembryonic antigen (anti-CEA) in various tumors. 152 pathologically confirmed patients with a tumor were imaged prior to surgery with an anti-CEA monoclonal antibody labeled with 99 Tc. There were 115 patients with ovarian carcinoma, 26 patients with colorectal carcinoma and 11 patients with lung carcinoma. Images were acquired at 3-6 h post injection and were analyzed by the double blind method. Images of patients with ovarian cancer were compared with B-ultrasound images. Immunohistochemical staining was performed on all cases of colorectal cancer. All RII images demonstrated excellent contrast, clear lesions, and no serious toxic or other side reactions occurred. Transient chills and fever were observed in 3 cases. This study showed a sensitivity=88.2%, specificity=83.2%, and an accuracy=4.0%. The smallest lesion size detected was 2 x 2 cm. The total combined lesion detection rate for primary, metastatic, and recurrence lesions was 84.4%. We conclude that 99 Tc labeled anti-CEA MoAb C50 can be used in the diagnosis of colorectal carcinoma, ovarian carcinoma, and lung carcinoma

  2. 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

  3. Experimental study of biotin-avidin pretargeting technique for anti-CEA McAb radioimmunoimaging

    International Nuclear Information System (INIS)

    Sun Jianzhong; Zhu Chengmo; Guan Liang; Li Biao; Zhang Jixian; Shi Ailan; Zhang Suyin

    1996-01-01

    Biotin-avidin pretargeting technique was used in promoting the diagnostic efficacy of anti-CEA McAb radioimmunoimaging. CEA McAb was conjugated with biotin McAb (B-McAb), streptavidin (SA) was labeled with 131 I ( 131 I-SA) and DTPA-biotin with 111 In( 111 In-DTPA-B). Experimental human colonic tumor bearing nude mice were used. Two step method: B-McAb was preinjected, followed by 131 I SA 48h later, 24, 48, 96 and 120 h postinjection, γ-imaging and biodistribution were studied. Three step method: B-McAb was preinjected, followed by cold SA 24h later and 111 In-DTPA-B another 24h later. 2,6,24 and 48h postinjection, γ-imaging and biodistribution were also studied. Two step method: T/NT of all organs in experimental group was significantly increased compared with controls. The blood T/NT in experimental group and control group at 24 and 120h was 1.11:0.42 and 8.58:3.51, respectively. Tumor % ID/g in all organs slightly decreased compared with direct group. In γ-imaging radioactivity has been accumulated in tumor site as early as 24h, while only slightly visualized or non-visualized in controls. Three step method: in experimental group the blood T/NT reached 4.19 at 2 h, whereas all was < 1.37 at each phase of controls, the T/NT of all organs was also higher in experimental grouped than in controls. The tumor % ID/g in experimental group was 9.72% at 2h and 3.65% at 48h whereas % ID/g in controls in all phases was <3.07. The tumor clearly visualized at 2h and clearer at 48h in γ-imaging. In controls, the tumor was slightly visualized also to early stage, but faded away later on. Biotin-avidin pretargeting technique can elevate the T/NT ratio and decrease the blood background. Early imaging was obtained with better imaging quality

  4. 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

  5. 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.

  6. Development of instant kits 99Tcm-labelling of anti-CEA antibody and hIgG for scintigraphy

    International Nuclear Information System (INIS)

    Boonkittcharoen, V.

    1998-01-01

    99 Tc m -labelled monoclonal antibodies (MAbs) and human immunoglobulins (hIgG) have recently emerged as a new class of site specific radiopharmaceuticals. The role of 99 Tc m -labelled MAbs particularly anti-CEA IgG in tumour imaging has essentially established for early revealing of occult lesions in patients. Superiority of the method over X ray CT has been addressed for its capability in differentiating post-operation fibrosis from viable tumour. At present data, instant kits for preparation of this particular class of radiopharmaceuticals can be obtained from commercial sources but unfortunately at high prices. This prohibits the use of these promising diagnostic agents in developing country like Thailand. Under the assistance from IAEA through a research coordinating program, we worked on the 99 Tc m -radiochemistry in immunoglobulin labelling to establish the knowledge and acquire the know how in the development of in-house instant kits at low cost to serve the local nuclear medicine clinics in diagnosis of infectious and neoplastic diseases

  7. Radioimmunotherapy of Nude Mice Bearing Human Colon Carcinoma with I-131 Labeled Anti-carcinoembryonic Antigen

    International Nuclear Information System (INIS)

    Kim, Byung Tae; Lee, Kyung Han; Kim, Sang Eun; Choi, Yong; Chi, Dae Yoon; Chung, June Key; Lee, Myung Chul; Koh, Chang Soon; Chung, Hong Keun

    1995-01-01

    This study was designed to evaluate the effects of various factors on the therapeutic effect of the I-l3l labeled anti-carcinoembryonic antigen monoclonal antibody(anti-CEA antibody). Tetrazolium-based colorimetric assay (MTT) was used to compare in vitro cytotoxicity of 3 Korean colon cancer cell lines (SNU-C2A, SNU-C4, SNU-C5) for selection of proper 2 cell lines in this study. The changes of the size of tumor which was xenografted to nude mice (balb/c nu/nu) were compared in 4 groups (group treated I-131 labeled anti-CEA antibody, group treated with non-radiolabeled anti-CEA antibody, group treated with I-131. labeled anti-human chorionic gonadotropin monoclonal antibody (anti-hCG antibody) as nonspecific antibody, and group injected with normal saline as a control). Immunohistochemical staining and in vivo autoradiography were performed after excision of the xenografted tumor. The results were as below mentioned. The in vitro cytotoxic effect of I-131 labeled anti-CEA antibody is most prominent in SNU-C5 cell line between 3 cancer cell lines. The changes of xenografted tumor size in both SNU-C4 and SNU-C5 cell tumors at the thirteenth day after injection of the antibodies were smallest in the group treated with I-131 labeled anti-CEA antibody (SNU-C4/SNU-C5; 324/342%) comparing with other groups, group treated with anti-CEA antibody (622/660%), group treated with I-131 anti-hCG antibody (538/546%), and control group(1030/724%) (p<0.02 in SNU-C4 and p<0.1in SNU-C5 at the 13th day after injection of antibodies). On the thirteenth day after injection of the antibodies nude mice were sacreficed to count the radiouptake of tumor and to check the changes of tumor size. Correlations between radiouptake and change of tumor size were calculated in each groups and significant negative correlation was only obtained in the group treated with I-131 anti-CEA antibody (p<0.05). There were no correlations between antigenic expression of carcinoembryonic antigen and

  8. 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

  9. 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)

  10. Clinical experience of the radioimmunoscintigraphy with the 123-I-anti-CEA-Fab(No. 35)-fragment

    International Nuclear Information System (INIS)

    Meili, A.; Bekier, A.; Schulthess, G.K. von; Mach, J.P.

    1986-01-01

    Purified monoclonal murine 123-I-Fab-anti-CEA(Nr.35) were applied to 7 patients in a prospective study. Compared with the previous tested intact 131-I-labelled antibody (Nr. 202) the new preparation had many advantages for imaging: 2.7 times more counting efficiency of the gamma camera, higher activity utilizable and better accumulation in the tumor with sufficient image contrast in the ECT. Fifteen until sixteen hours after administration of 20 mCi 123-I the countrate in the pelvis was 130000/20 sec. In all patients the primary tumor was visualized, two patients demonstrated regional lymph node involvement and one patient liver metastasis in the left lobe. All findings were confirmed by surgery and histopathology. The average tumor/mucosa ratio was 3.5:1. The activity in the tumor 15 h after application was 0.015 per cent/g tumor/mCi 123-I used. 4/7 patients with colorectal cancer over 3.5 cm in diameter demonstrated normal plasma values of CEA < 3 microg/l. One patient with rising CEA plasma level was suspected of relapse, the focal accumulation corresponded with a mass lesion in the right sacrum in CT-scan. After the preliminary results the further applicability is recognizable: staging and screening before and after therapy, handicapped by high costs at time. A good advantage is the possibility of specific and organ independent diagnosis of tumor, which contents the corresponding surface antigen. (author)

  11. Radioimmunoscintigraphy with 99mTc-labelled anti-CEA monoclonal antibodies in colorectal carcinoma patients

    International Nuclear Information System (INIS)

    Sergieva, S.; Baychev, G.; Tzingilev, D.; Delijski, T.; Kirova, G.; Kirilova, B.; Nenovska, M.

    1998-01-01

    Sixteen patients (2 female and 14 male, aged 42-75) were given intravenous injections with 99m Tc (555-740 MBq)-labelled anti-CEA MAb (CEA-Scan, Mallinckrodt Medical and M-CEATEC, Sorin Biomedica). Five of them were with duly established or established or suspected primary colorectal carcinoma, and eleven were studied postoperatively after recording an increase CEA levels in serum. The patients were scanned within 4-24 h of infusion using planar and tomographic imaging in rotation gamma-camera DIACAM (Siemens). At all 16 patients 27 true positive results were obtained: in 7 primary colorectal carcinomas, 5 locally recurrent tumors, 7 liver metastases, 6 lymphogeneous lesions and two - in the ureteral region. True negative results were established at three patients, false positive - in one patient with chronic inflammation, and false negative results - in 3 cases with liver metastases foci < 8 mm. Having 90 % sensitivity, 75 % specificity and 82.3 % accuracy, radioimmunoscintigraphy is a highly informative and sensitive imaging method for diagnosing and following up of primary, recurrent and metastatic foci in colorectal carcinoma patients. (author)

  12. The biodistribution study of 99mTc labelled anti-CEA monoclonal antibody in tumor bearing nude mice

    International Nuclear Information System (INIS)

    Lou Zongxin

    1992-01-01

    The author report the optimal condition of 99m Tc labelling with anti-CEA monoclonal antibody using chelating of 99m Tc with dimethylformamide. The labelling rate of this method is 60%-80%, the radiochemical purity of labelling antibody over 90% and maintain its better immuno activity. The biodistribution of the tumor bearing nude mice demonstrates that as compared with the control group, 24 hours after the intraperitoneal injection the injected labelled antibody has its specific concentration in tumor tissue

  13. 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

  14. 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

  15. 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

  16. Anti-CEA aptamers labeled with {sup 99m}Tc: encapsulation studies in long-circulating and pH-sensitive liposomes, biodistribution and imaging

    Energy Technology Data Exchange (ETDEWEB)

    Leonel, M.F.V.; Andrade, A.S.R. [Centro de Desenvolvimento da Tecnologia Nuclear (CDTN/CNEN-MG), Belo Horizonte, MG (Brazil); Oliveira, M.C.; Cardoso, V.N.; Barros, A.L.B. [Universidade Federal de Minas Gerais (UFMG), Belo Horizonte, MG (Brazil). Faculdade de Farmacia

    2015-07-01

    Colorectal cancer (CRC) is one of the leading cancers and the carcinoembryonic antigen (CEA) is a tumor marker widely used in diagnosis since it is overexpressed in tumor cells. Acid nucleic aptamers with high affinity and specificity for this antigen become promising molecules for CRC diagnosis by imaging. However, due to the action of nucleases in vivo, they have been investigated for association with liposomes, such as long-circulating and pH-sensitive liposomes (SPHL) that can be destabilized in the tumor region releasing aptamers and contributing to the CRC diagnosis by scintigraphy. In this work, SpHL containing DOPE, CHEMS and mPEG{sub 2000}-DSPE were characterized by analyzing mean diameter, polydispersity index and zeta potential. The anti-CEA aptamers Apt3 and Apt3-Amino were labeled with technetium-99m and the encapsulation efficiency (EE) of {sup 99m}Tc-Apt3 in the SpHL by dehydration-rehydration (modified DRV) and freeze-thaw (FT) were analyzed, both in the presence of cryoprotectants. Biodistribution and scintigraphic images were performed at 1h and 4h post-injection of {sup 99m}Tc-Apt3-amino, {sup 99m}Tc-Apt3-SpHL or {sup 99m}Tc-Apt3-amino-SpHL complexes in Balb/c healthy mice. The SpHL dispersions were homogeneous. The radiolabeling yield with technetium-99m was over 90% for all complexes. By the dehydration-rehydration method, the SpHL increased over 200% after encapsulation procedure. By the freeze-thaw method, the SpHL size increased only 13.7%. Free {sup 99m}Tc-Apt3-amino showed to be cleared by renal via with high levels of radioactivity in the kidney and bladder, however, the {sup 99m}Tc-Apt3-SpHL and {sup 99m}Tc-Apt3-amino-SpHL clearly indicated high uptake by liver and spleen. The biodistribution of {sup 99m}Tc-Apt3-SpHL showed significant uptake of radioactivity by stomach and thyroid indicating less stability of the Apt3 radiolabelling in relation to Apt3-amino. (author)

  17. Anti-CEA aptamers labeled with 99mTc: encapsulation studies in long-circulating and pH-sensitive liposomes, biodistribution and imaging

    International Nuclear Information System (INIS)

    Leonel, M.F.V.; Andrade, A.S.R.; Oliveira, M.C.; Cardoso, V.N.; Barros, A.L.B.

    2015-01-01

    Colorectal cancer (CRC) is one of the leading cancers and the carcinoembryonic antigen (CEA) is a tumor marker widely used in diagnosis since it is overexpressed in tumor cells. Acid nucleic aptamers with high affinity and specificity for this antigen become promising molecules for CRC diagnosis by imaging. However, due to the action of nucleases in vivo, they have been investigated for association with liposomes, such as long-circulating and pH-sensitive liposomes (SPHL) that can be destabilized in the tumor region releasing aptamers and contributing to the CRC diagnosis by scintigraphy. In this work, SpHL containing DOPE, CHEMS and mPEG 2000 -DSPE were characterized by analyzing mean diameter, polydispersity index and zeta potential. The anti-CEA aptamers Apt3 and Apt3-Amino were labeled with technetium-99m and the encapsulation efficiency (EE) of 99m Tc-Apt3 in the SpHL by dehydration-rehydration (modified DRV) and freeze-thaw (FT) were analyzed, both in the presence of cryoprotectants. Biodistribution and scintigraphic images were performed at 1h and 4h post-injection of 99m Tc-Apt3-amino, 99m Tc-Apt3-SpHL or 99m Tc-Apt3-amino-SpHL complexes in Balb/c healthy mice. The SpHL dispersions were homogeneous. The radiolabeling yield with technetium-99m was over 90% for all complexes. By the dehydration-rehydration method, the SpHL increased over 200% after encapsulation procedure. By the freeze-thaw method, the SpHL size increased only 13.7%. Free 99m Tc-Apt3-amino showed to be cleared by renal via with high levels of radioactivity in the kidney and bladder, however, the 99m Tc-Apt3-SpHL and 99m Tc-Apt3-amino-SpHL clearly indicated high uptake by liver and spleen. The biodistribution of 99m Tc-Apt3-SpHL showed significant uptake of radioactivity by stomach and thyroid indicating less stability of the Apt3 radiolabelling in relation to Apt3-amino. (author)

  18. 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

  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. An alternative procedure for incorporating radiolabelled cholesteryl ester into human plasma lipoproteins in vitro

    International Nuclear Information System (INIS)

    Roberts, D.C.K.; Miller, N.E.; Price, S.G.L.; Crook, D.; Cortese, C.; Ville, A. La; Masana, L.; Lewis, B.

    1985-01-01

    A simple method has been developed for labelling human plasma lipoproteins to high specific radioactivity with radioactive cholesteryl esters in vitro. After isolation by preparative ultracentrifugation, the selected lipoprotein was incubated for 30 min at 4 0 C in human serum (d > 1.215) that had been prelabelled with [4- 14 C]cholesteryl oleate or [1,2- 3 H]cholesteryl linoleate, and was then re-isolated by ultracentrifugation. All major lipoprotein classes were labelled by the procedure. Specific radioactivities of up to 18 d.p.m. .pmol -1 (46d.p.m. .ng -1 ) were achieved. When radiolabelled high-density lipoprotein was infused intravenously, the radioactive cholesteryl ester behaved in vivo indistinguishably from endogenous cholesteryl esters produced by the lecithin (phosphatidylcholine): cholesterol acyltransferase reaction. (author)

  1. A radiolabeled antiglobulin assay to identify human cervical mucus immunoglobulin (Ig) A and IgG antisperm antibodies

    International Nuclear Information System (INIS)

    Haas, G.G. Jr.; D'Cruz, O.J.

    1989-01-01

    Antisperm immunoglobulin (Ig) A and IgG antibodies in human cervical mucus (CM) were identified by a radiolabeled antiglobulin assay. Cervical mucus samples from fertile and infertile women were exposed to a 1:3,200 dilution of 2-mercaptoethanol (2-ME), and 5 micrograms of the solubilized CM protein were assayed for the presence of IgA and IgG antisperm and anti-Candida activity by the radiolabeled antiglobulin assay. Purified human secretory IgA and IgG exposed to 2-ME retained the molecular integrity and functional activity of the untreated antibody molecules. CM aliquots collected after high-performance liquid chromatography (HPLC) fractionation were assessed for antisperm antibody activity; antisperm antibody activity was retained in the appropriate IgA or IgG CM fractions. The incidence of CM antisperm antibodies was minimally affected when the radiolabeled antiglobulin assay was performed with a motile sperm population. Approximately 70% of the CM IgA antisperm antibodies were of the IgA1 subclass; CM IgG was primarily of the IgG4 subclass. When Candida antigen was substituted for sperm in the radiolabeled antiglobulin assay, the CM antisperm antibodies were found to be exclusively sperm-specific. These data indicate that the radiolabeled antiglobulin assay using 2-ME to extract CM antibodies is a specific method for the assay of antisperm antibodies in CM

  2. Biodistribution parameters and radiation absorbed dose estimates for radiolabeled human low density lipoprotein

    International Nuclear Information System (INIS)

    Hay, R.V.; Ryan, J.W.; Williams, K.A.; Atcher, R.W.; Brechbiel, M.W.; Gansow, O.A.; Fleming, R.M.; Stark, V.J.; Lathrop, K.A.; Harper, P.V.

    1992-01-01

    The authors propose a model to generate radiation absorbed dose estimates for radiolabeled low density lipoprotein (LDL), based upon eight studies of LDL biodistribution in three adult human subjects. Autologous plasma LDL was labeled with Tc-99m, I-123, or In-111 and injected intravenously. Biodistribution of each LDL derivative was monitored by quantitative analysis of scintigrams and direct counting of excreta and of serial blood samples. Assuming that transhepatic flux accounts for the majority of LDL clearance from the bloodstream, they obtained values of cumulated activity (A) and of mean dose per unit administered activity (D) for each study. In each case highest D values were calculated for liver, with mean doses of 5 rads estimated at injected activities of 27 mCi, 9 mCi, and 0.9 mCi for Tc-99m-LDL, I-123-LDL, and In-111-LDL, respectively

  3. Radiolabelled anti-human fibrin antibody: a new thrombus-detecting agent

    International Nuclear Information System (INIS)

    Bosnjakovic, V.; Jankovic, B.D.; Horvat, J.; Cvoric, J.

    1977-01-01

    Rabbit anti-human fibrin globulin (A.F.G.) was labelled with iodine ( 131 I) and used as a thrombus-detecting agent. 131 I-A.F.G. labelled thrombi were displayed by means of a gamma scintillation camera. Normal subjects and patients with thrombo-phlebitis of legs, acute fibrin depositions other than thrombi, and chronic varicosities were examined. The 131 I-A.F.G. technique detected both formed thrombi and those that were forming and could discriminate between acute thrombosis and chronic varicosities. Thrombo-phlebitis and extravascular fibrin depositions were best demonstrated between 24 and 72 hours after 131 I-A.F.G. injection. Radiolabelled A.F.G. in normal veins and chronic varicosities was best displayed within 6 hours of injection. (author)

  4. The spreading of radiolabelled fatty suppository bases in the human rectum

    International Nuclear Information System (INIS)

    Sugito, Keiko; Ogata, Hiroyasu; Noguchi, Masahiro; Kogure, Takahashi; Takano, Masaaki; Maruyama, Yuzo; Sasaki, Yasuhito

    1988-01-01

    The purpose of this study was to develop a radiolabelling method for assessing the spreading of fatty suppository bases (Witepsol H-5, W-35 and S-55), and to apply this technique to the evaluation of suppository disposition in the human rectum. 99m/Tc was bound chemically to the bases Witepsol H-5 and W-35, and mixed physically with Witepsol S-55. The spreading of each suppository base was monitored by gamma-scintigraphy following rectal administration. The mean radioactivity remaining at the inserted region 4 h after administration was 44.2% of total activity. The mean perpendicular maximum spreading distance from this region was 7.7 cm on the scintigram near to the sigmoid colon. Defecation was suggested to be a factor influencing the spread of suppository bases. However, there was no clear relationship between the type of suppository base used and the extent of its spread within the rectum. 6 refs.; 4 figs.; 1 table

  5. The clinical application of radioimmunoimaging with 99mTc labeled anti-CEA monoclonal antibody C50

    International Nuclear Information System (INIS)

    Jiang Ningyi; Sha Xiaozhen; Zhang Hua

    1996-01-01

    To evaluate the clinical value of the radioimmunoimaging (RII) for the diagnosis of tumor with 99m Tc labeled anti-CEA monoclonal antibody C50, C50 was labeled with 99m Tc using modified 2-mercaptoethanol method. 99m Tc-C50 RII was performed in 70 patients with tumor. All were pathologically proved after operation. The sensitivity of 99m Tc-C50 RII for tumor was 82.9%, the specificity was 86.2%, the false negative rate was 17.1%, and the false positive rate was 13.8%. The positive predictive value was 89.5%, the negative predictive value was 78.1%. The coincidence rates was 82.4%, 84.6% and 80.0% for the ovarial intestinal and lung tumor respectively. 99m Tc-C50 RII was useful in clinical diagnosis of tumor

  6. The importance of tumor marker titers for the indication of immunoscintigraphy with monoclonal antibodies anti-CEA and anti-CA 19.9

    International Nuclear Information System (INIS)

    Bouvier, J.F.; Charrie, A.; Fleury-Goyon, M.C.; Chauvot, P. et; Lahneche, B.E.

    1986-01-01

    In 18 patients operated for malignant tumors 20 immunoscintigraphies were done with a monoclonal antibody cocktail (anti-CEA F(ab') 2 and anti-CA 19.9 F(ab') 2 ). Immediately before scintigraphy tumor marker titers in plasma were determined in all cases. Tumor marker levels corresponding to positive or doubtful scintigraphies are analysed. (Author)

  7. Quantification of the fate of dietary fiber in humans by a newly developed radiolabeled fiber marker

    International Nuclear Information System (INIS)

    Carryer, P.W.; Brown, M.I.; Malagelada, J.R.; Carlson, G.L.; McCall, J.T.

    1982-01-01

    A radiolabeled cellulose ( 131 I-fiber) that retains the essential physical and chemical properties of this class of fiber was developed in our laboratory. Researchers quantified the fate of orally ingested 131 I-fiber in healthy individuals by external gamma camera monitoring and fecal collections. The marker passes virtually intact through the human gastrointestinal tract with negligible release and absorption of the label in the gut. Comparison of the gastric emptying rate of 131 I-fiber with that of a predominantly aqueous marker, 99 mTc-diethylenetriamine pentaacetic acid ( 99 mTc-DTPA), showed that 131 I-fiber strands were evacuated more slowly than intragastric fluids. An important finding was that some 131 I-fiber emptying occurred during most time periods, even before liquids were completely evacuated. This suggests that the human stomach is able to empty simultaneously liquids and fiber strands (1-15 mm in length) that are resistant to grinding by antral mechanical forces and to digestion by acid-peptic secretion. Thus, some nondigestible solids may be emptied with the bulk of a meal, although at a slower rate. 131 I-Fiber may be a useful marker for quantifying gastric emptying of nondigestible solids. Further, the stability of 131 I-fiber in the gut, as opposed to most other physiologic solid labels, should enable future investigation of intestinal and colonic transit of fiber, which is an important component of the human diet

  8. Quantification of the fate of dietary fiber in humans by a newly developed radiolabeled fiber marker

    Energy Technology Data Exchange (ETDEWEB)

    Carryer, P.W.; Brown, M.I.; Malagelada, J.R.; Carlson, G.L.; McCall, J.T.

    1982-06-01

    A radiolabeled cellulose (/sup 131/I-fiber) that retains the essential physical and chemical properties of this class of fiber was developed in our laboratory. Researchers quantified the fate of orally ingested /sup 131/I-fiber in healthy individuals by external gamma camera monitoring and fecal collections. The marker passes virtually intact through the human gastrointestinal tract with negligible release and absorption of the label in the gut. Comparison of the gastric emptying rate of /sup 131/I-fiber with that of a predominantly aqueous marker, /sup 99/mTc-diethylenetriamine pentaacetic acid (/sup 99/mTc-DTPA), showed that /sup 131/I-fiber strands were evacuated more slowly than intragastric fluids. An important finding was that some /sup 131/I-fiber emptying occurred during most time periods, even before liquids were completely evacuated. This suggests that the human stomach is able to empty simultaneously liquids and fiber strands (1-15 mm in length) that are resistant to grinding by antral mechanical forces and to digestion by acid-peptic secretion. Thus, some nondigestible solids may be emptied with the bulk of a meal, although at a slower rate. /sup 131/I-Fiber may be a useful marker for quantifying gastric emptying of nondigestible solids. Further, the stability of /sup 131/I-fiber in the gut, as opposed to most other physiologic solid labels, should enable future investigation of intestinal and colonic transit of fiber, which is an important component of the human diet.

  9. Selective radiolabeling and isolation of the hydrophobic membrane-binding domain of human erythrocyte acetylcholinesterase

    International Nuclear Information System (INIS)

    Roberts, W.L.; Rosenberry, T.L.

    1986-01-01

    The hydrophobic, membrane-binding domain of purified human erythrocyte acetylcholinesterase was labeled with the photoactivated reagent 3-(trifluoromethyl)-3-(m-[ 125 I]iodophenyl)diazirine. The radiolabel was incorporated when the enzyme was prepared in detergent-free aggregates, in detergent micelles, or in phospholipid liposomes, but the highest percentage of labeling occurred in the detergent-free aggregates. Papain digestion of the enzyme released the hydrophobic domain, and polyacrylamide gel electrophoresis in sodium dodecyl sulfate or gel exclusion chromatography demonstrated that the label was localized exclusively in the cleaved hydrophobic domain fragment. This fragment was purified in a three-step procedure. Digestion was conducted with papain attached to Sepharose CL-4B, and the supernatant was adsorbed to acridinium affinity resin to remove the hydrophilic enzyme fragment. The nonretained fragment associated with Triton X-100 micelles was then chromatographed on Sepharose CL-6B, and finally detergent was removed by chromatography on Sephadex LH-60 in an ethanol-formic acid solvent. The fragment exhibited an apparent molecular weight of 3100 on the Sephadex LH-60 column when compared with peptide standards. However, amino acid analysis of the purified fragment revealed only 1 mol each of histidine and glycine per mole of fragment in contrast to the 25-30 mole of amino acids expected on the basis of the molecular weight estimate. This result suggests a novel non-amino acid structure for the hydrophobic domain of human erythrocyte acetylcholinesterase

  10. Radiolabelled GLP-1 receptor antagonist binds to GLP-1 receptor-expressing human tissues

    Energy Technology Data Exchange (ETDEWEB)

    Waser, Beatrice; Reubi, Jean Claude [University of Berne, Division of Cell Biology and Experimental Cancer Research, Institute of Pathology, PO Box 62, Berne (Switzerland)

    2014-06-15

    Radiolabelled glucagon-like peptide 1 (GLP-1) receptor agonists have recently been shown to successfully image benign insulinomas in patients. For the somatostatin receptor targeting of tumours, however, it was recently reported that antagonist tracers were superior to agonist tracers. The present study therefore evaluated various forms of the {sup 125}iodinated-Bolton-Hunter (BH)-exendin(9-39) antagonist tracer for the in vitro visualization of GLP-1 receptor-expressing tissues in rats and humans and compared it with the agonist tracer {sup 125}I-GLP-1(7-36)amide. Receptor autoradiography studies with {sup 125}I-GLP-1(7-36)amide agonist or {sup 125}I-BH-exendin(9-39) antagonist radioligands were performed in human and rat tissues. The antagonist {sup 125}I-BH-exendin(9-39) labelled at lysine 19 identifies all human and rat GLP-1 target tissues and GLP-1 receptor-expressing tumours. Binding is of high affinity and is comparable in all tested tissues in its binding properties with the agonist tracer {sup 125}I-GLP-1(7-36)amide. For comparison, {sup 125}I-BH-exendin(9-39) with the BH labelled at lysine 4 did identify the GLP-1 receptor in rat tissues but not in human tissues. The GLP-1 receptor antagonist exendin(9-39) labelled with {sup 125}I-BH at lysine 19 is an excellent GLP-1 radioligand that identifies human and rat GLP-1 receptors in normal and tumoural tissues. It may therefore be the molecular basis to develop suitable GLP-1 receptor antagonist radioligands for in vivo imaging of GLP-1 receptor-expressing tissues in patients. (orig.)

  11. Radiolabelled GLP-1 receptor antagonist binds to GLP-1 receptor-expressing human tissues

    International Nuclear Information System (INIS)

    Waser, Beatrice; Reubi, Jean Claude

    2014-01-01

    Radiolabelled glucagon-like peptide 1 (GLP-1) receptor agonists have recently been shown to successfully image benign insulinomas in patients. For the somatostatin receptor targeting of tumours, however, it was recently reported that antagonist tracers were superior to agonist tracers. The present study therefore evaluated various forms of the 125 iodinated-Bolton-Hunter (BH)-exendin(9-39) antagonist tracer for the in vitro visualization of GLP-1 receptor-expressing tissues in rats and humans and compared it with the agonist tracer 125 I-GLP-1(7-36)amide. Receptor autoradiography studies with 125 I-GLP-1(7-36)amide agonist or 125 I-BH-exendin(9-39) antagonist radioligands were performed in human and rat tissues. The antagonist 125 I-BH-exendin(9-39) labelled at lysine 19 identifies all human and rat GLP-1 target tissues and GLP-1 receptor-expressing tumours. Binding is of high affinity and is comparable in all tested tissues in its binding properties with the agonist tracer 125 I-GLP-1(7-36)amide. For comparison, 125 I-BH-exendin(9-39) with the BH labelled at lysine 4 did identify the GLP-1 receptor in rat tissues but not in human tissues. The GLP-1 receptor antagonist exendin(9-39) labelled with 125 I-BH at lysine 19 is an excellent GLP-1 radioligand that identifies human and rat GLP-1 receptors in normal and tumoural tissues. It may therefore be the molecular basis to develop suitable GLP-1 receptor antagonist radioligands for in vivo imaging of GLP-1 receptor-expressing tissues in patients. (orig.)

  12. Radiolabeling of human platelets using four radiopharmaceuticals with Tc-99m

    International Nuclear Information System (INIS)

    Portillo L, M.C.; Godoy, C.

    1991-01-01

    The present investigation work has been done in an evaluation of four different radiopharmaceuticals with Tin II (Glucoheptonate, Pyrophosphate, Citrate and DTPA), with the purpose of determining which one of the four would be obtained a higher rate of radiolabeling of platelets with Tc-99m. In order to evaluate the four radiopharmaceuticals it was procede to the separation and labeling of the human platelets. It was worked with samples of blood from five pacients, and the platelets from each one of them were labeled with the radiopharmaceuticals-Tc-99m. Then was observed a significant difference among the four radiopharmaceuticals studied, with a reliable level of 0.05 being the Glucoheptonate-Tc-99m the best to label platelets, obtaining with the same 50.23% of labeling efficiency, while for DTPA, Pyrophosphate and Citrate, It was obtained 33.42%, 29.82% and |2.62% respectively. Also, it was studied the biodistribution of the labeled platelets, using Glucoheptonate-Tc-99m as a radiopharamceutical. The biodistribution was studied in white mice at different times and it was founded that the place of biodistribution of the labeled platelets is given in greater percentage in the liver, spleen, lungs and kydneis. (Author)

  13. 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

  14. Studies on binding of radiolabeled thyrotropin to cultured human thyroid cells

    International Nuclear Information System (INIS)

    Yamamoto, M.; Rapoport, B.

    1978-01-01

    A line of cultured human thyroid adenoma cells was used in a study designed to compare the stimulatory effect of TSH on cellular cAMP generation with the binding of radiolabeled TSH to the cells. At 37 C, specific binding of [ 125 I]TSH to suspensions of thyroid cells was maximal at 20 min and was reversed by the addition of excess TSH. Unlike the generation of cellular cAMP in response to TSH stimulation, which was maximal at pH 7.5, the binding of [ 125 ]TSH to the cells was maximal at pH 5.5 and progressively declined up to pH 8.5. Increasing NaCl concentrations progressively inhibited cellular binding of TSH; at physiological salt concentrations, almost no TSH binding was detectable. Competitive inhibition studies of [ 125 I]TSH binding to cells revealed a binding site with a dissociation constant of 5.5 x 10 -8 M at pH 7.4. GH, PRL, hCG, FSH, insulin, and glucagon did not compete with [ 125 I)TSH binding. ACTH, however, was a potent inhibitor of [ 125 I]TSH binding. Despite this inhibitory effect on TSH binding, ACTH had little or no effect on cellular cAMP generation. High concentrations of ACTH did not inhibit the biological effect of TSH on cAMP generation. Specific binding of [ 125 I]TSH to empty plastic culture dishes was time dependent, reversible, and displayed a hormonal specificity identical to binding to thyroid cells. The effects of pH and NaCl concentrations on TSH binding to dishes were similarbut not identical to those on cellular binding. This study raises serious questions as to the biological significance of [ 125 I]TSH binding to cultured human thyroid cells

  15. Diagnosis of colorectal carcinomas and recurrence with 99m Tc labeled monoclonal anti-CEA-antibody (BW 431/26)

    International Nuclear Information System (INIS)

    Lind, P.; Langsteger, W.; Koeltringer, P.; Eber, O.; Beham, A.

    1989-01-01

    With the introduction of 99m Tc labeled monoclonal antibodies against CEA, a clinically relevant extension can be expected in the diagnosis of colorectal tumors by immunoscintigraphy (IS). This study comprises a total of 31 patients (primary tumors, occult neoplasms with elevated CEA serum level, suspicious recurrences). In primary tumors (n = 14), all coloscopically diagnosed carcinomas were confirmed and correctly localised by IS (n = 8). In 4 cases IS was true negative, in one case false positive; in one patient a stomach adenocarcinoma could be demonstrated. In the diagnosis of recurrences (n = 17) IS revealed an uptake in TCT (transmission computed tomography) and coloscopically suspicious areas in 10 cases. In 6 cases IS was negative (5 true negative findings in scar or granulation tissue, 1 false negative finding in paraaortal lymphnodes). In one patient the raised CEA level was due to multiple liver metastases, a local recurrence could not be detected. Elevated serum CEA-levels were found only in 10 of 19 patients with true positive IS. In postoperative cancer care IS with 99m Tc-labeled anti-CEA antibody (MAK BW 431/26) plays a preeminent role in the exclusion or diagnosis of kolorectal recurrences in case of ambiguous TCT or endoscopic findings. (Author)

  16. Liver myeloid-derived suppressor cells expand in response to liver metastases in mice and inhibit the anti-tumor efficacy of anti-CEA CAR-T

    Science.gov (United States)

    Burga, Rachel A.; Thorn, Mitchell; Point, Gary R.; Guha, Prajna; Nguyen, Cang T.; Licata, Lauren A.; DeMatteo, Ronald P.; Ayala, Alfred; Espat, N. Joseph; Junghans, Richard P.; Katz, Steven C.

    2015-01-01

    Chimeric antigen receptor modified T cell (CAR-T) technology, a promising immunotherapeutic tool, has not been applied specifically to treat liver metastases (LM). While CAR-T delivery to LM can be optimized by regional intrahepatic infusion, we propose that liver CD11b+Gr-1+ myeloid-derived suppressor cells (L-MDSC) will inhibit the efficacy of CAR-T in the intrahepatic space. We studied anti-CEA CAR-T in a murine model of CEA+ LM and identified mechanisms through which L-MDSC expand and inhibit CAR-T function. We established CEA+ LM in mice and studied purified L-MDSC and responses to treatment with intrahepatic anti-CEA CAR-T infusions. L-MDSC expanded three-fold in response to LM and their expansion was dependent on GM-CSF, which was produced by tumor cells. L-MDSC utilized PD-L1 to suppress anti-tumor responses through engagement of PD-1 on CAR-T. GM-CSF, in cooperation with STAT3, promoted L-MDSC PD-L1 expression. CAR-T efficacy was rescued when mice received CAR-T in combination with MDSC depletion, GM-CSF neutralization to prevent MDSC expansion, or PD-L1 blockade. As L-MDSC suppressed anti-CEA CAR-T, infusion of anti-CEA CAR-T in tandem with agents targeting L-MDSC is a rational strategy for future clinical trials. PMID:25850344

  17. Selection of monoclonal anti-CEA antibody fragments for tumor detection by immunoscintigraphy

    International Nuclear Information System (INIS)

    Mach, J.P.; Buchegger, F.

    1986-01-01

    It is described how individual MAb directed against carcinoembryotic antigen (CEA) is selected which does not crossreact with granulocytes and gives the best tumor localization in the model of nude mice grafted with human colon carcinoma. Using this model, the superiority of F(ab')/sub 2/ and particularly Fab fragments from high affinity MAb for the localization of relatively small tumor nodules is demonstrated. These MAb fragments are also successfully used in an ongoing clinical trial for the detection of primary and metastatic colorectal carcinomas

  18. 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

  19. Immunoscintigraphy of adenocarcinomas by means of 111In-labelled F(ab')2 fragments of anti-CEA monoclonal antibody F023C5

    International Nuclear Information System (INIS)

    Riva, P.; Paganelli, G.; Callegaro, L.

    1988-01-01

    F(ab') 2 fragments of F023C5, an anti-CEA monoclonal antibody, were conjugated to diethylenetriamine pentaacetic acid (DTPA) and converted into a ready to use reagent for instant 111 In-labelling. The resulting 111 In radiopharmaceutical was administered intravenously and tested for its ability to image (at 48-72 h after administration) 31 primary and 85 metastatic carcinoma lesions in 70 adenocarcinoma patients (26 gastrointestinal, 18 breast and 26 lung tumour patients) whose serum CEA was elevated in 43 cases and normal in the other 27. (author)

  20. Development of a kit lyophilized of Anti-CEA to be labeled with Tc-99m, radionuclide obtained by extraction with MEK, complemented with studies of stability

    International Nuclear Information System (INIS)

    Robles Nique, Anita E.

    2006-01-01

    The colorectal cancer places the sixth place in Peru, more than 350 persons are diagnosed annually with this illness, for that reason, the present work contributes with the development of a lyophilized kit of monoclonal antibody Anti-CEA to be labelled by the radionuclide Tc-99m, for the early diagnosis of tumours embryonic adenocarcinoma. For the lack of a generator of adsorption of 99 Mo / 99m Tc in the country, the Tc-99m is used instead of this, coming from a generator of extraction, that use the methylethylketone (MEK) like solvent. First, it was designed systematically 4 lyophilized formulations and through the determination of the radiochemical purity of 99m Tc-Anti-CEA, the effect of the molar relation has been evaluated of the MoAb: 2-ME (1:1000 and 1:2000), the increasing of the reductor agent (3,50 to 5,95 μg SnF2) and the reduced protein (1,0 to 1,2 mg Anti-CEA). Second. On the base of the evaluation of the results of these 4 lyophilized formulations, 4 experimental lots have been prepared. The developed methodology initiates with the reduction of the protein for the direct method with 2-ME, the purification in column of PD10, then the addition of the SnF 2 and MDP, finally the lyophilization. Lyophilized kit is labeled by Tc-99m by the direct method to obtain 99m Tc-Anti-CEA and the radiochemical purity is determined by chromatography in ITLC-SG and HPLC, activity support and volume of Tc-99m, biological distribution in healthy mice, immunoreactivity is determined by chromatography of affinity, challenge with L-cysteine determined by chromatography in ITLC-SG. It complements itself with studies of stability in real-time for the lyophilized kit and for 99m Tc-Anti-CEA. The results of the first part, its 1st; 2nd; 3rd and 4th lyophilized formulation had a radiochemical purity of 71, 92, 94 and 97 % respectively, to a pH of labelled between 7,0 to 7,5. The results of the second part, 4 experimental lots had in average of radiochemical purity more than 95

  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. 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)

  3. 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).

  4. Simultaneous assay for plasmin and DNase using radiolabeled human fibroblasts on microcarriers

    International Nuclear Information System (INIS)

    Boswell, G.S.; Dimitrijevich, S.D.; Gracy, R.W.

    1989-01-01

    A critical step in tissue and wound repair is the removal of eschar--accumulation of denatured cellular and extracellular macromolecules. Enzymatic debridement using a combination of plasmin (fibrinolysin) and DNase has been successfully utilized on a variety of types of wounds. Monitoring the activity of these enzymes by measuring the rate of fibrinolysis, or by viscometric changes due to DNA hydrolysis, is exceedingly cumbersome, time consuming, and, at best, only semiquantitative. Although spectrophotometric assays using synthetic substrates offer several advantages, they do not allow extrapolation of the data to the more complex natural substrates encountered in vivo. We have, therefore, developed an in vitro radioisotopic assay for the simultaneous and quantitative measurement of the hydrolytic activity of both plasmin and DNase. Double labeled ([3H]thymidine, [14C]leucine) human dermal fibroblasts grown on microcarrier beads are utilized as sources of nucleic acid and protein substrates. The assay meets all the criteria of analytical validity, is sensitive and rapid, and is amenable to adaptation for analysis of other hydrolytic enzymes. The method offers a direct evaluation of the enzymatic debridement of wounds using actual human cellular substrates. Moreover, the microcarriers provide a greatly increased surface area for cell attachment and growth, are amenable to rapid separation from the cells by simple mechanical methods, and are ideally suited to analytical manipulations

  5. 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.

  6. Radiolabeled pertuzumab for imaging of human epidermal growth factor receptor 2 expression in ovarian cancer

    Energy Technology Data Exchange (ETDEWEB)

    Jiang, Dawei [Shenzhen University, Guangdong Key Laboratory for Biomedical Measurements and Ultrasound Imaging, School of Biomedical Engineering, Shenzhen (China); University of Wisconsin - Madison, Department of Radiology, Madison, WI (United States); Im, Hyung-Jun [University of Wisconsin - Madison, Department of Radiology, Madison, WI (United States); Seoul National University, Graduate School of Convergence Science and Technology, Seoul (Korea, Republic of); Sun, Haiyan; Cho, Steve Y. [University of Wisconsin - Madison, Department of Radiology, Madison, WI (United States); Valdovinos, Hector F.; England, Christopher G.; Ehlerding, Emily B.; Nickles, Robert J. [University of Wisconsin - Madison, Department of Medical Physics, Madison, WI (United States); Lee, Dong Soo [Seoul National University, Graduate School of Convergence Science and Technology, Seoul (Korea, Republic of); Huang, Peng [Shenzhen University, Guangdong Key Laboratory for Biomedical Measurements and Ultrasound Imaging, School of Biomedical Engineering, Shenzhen (China); Cai, Weibo [University of Wisconsin - Madison, Department of Radiology, Madison, WI (United States); University of Wisconsin - Madison, Department of Medical Physics, Madison, WI (United States); University of Wisconsin Carbone Cancer Center, Madison, WI (United States)

    2017-08-15

    Human epidermal growth factor receptor 2 (HER2) is over-expressed in over 30% of ovarian cancer cases, playing an essential role in tumorigenesis and metastasis. Non-invasive imaging of HER2 is of great interest for physicians as a mean to better detect and monitor the progression of ovarian cancer. In this study, HER2 was assessed as a biomarker for ovarian cancer imaging using {sup 64}Cu-labeled pertuzumab for immunoPET imaging. HER2 expression and binding were examined in three ovarian cancer cell lines (SKOV3, OVCAR3, Caov3) using in vitro techniques, including western blot and saturation binding assays. PET imaging and biodistribution studies in subcutaneous models of ovarian cancer were performed for non-invasive in vivo evaluation of HER2 expression. Additionally, orthotopic models were employed to further validate the imaging capability of {sup 64}Cu-NOTA-pertuzumab. HER2 expression was highest in SKOV3 cells, while OVCAR3 and Caov3 displayed lower HER2 expression. {sup 64}Cu-NOTA-pertuzumab showed high specificity for HER2 (K{sub a} = 3.1 ± 0.6 nM) in SKOV3. In subcutaneous tumors, PET imaging revealed tumor uptake of 41.8 ± 3.8, 10.5 ± 3.9, and 12.1 ± 2.3%ID/g at 48 h post-injection for SKOV3, OVCAR3, and Caov3, respectively (n = 3). In orthotopic models, PET imaging with {sup 64}Cu-NOTA-pertuzumab allowed for rapid and clear delineation of both primary and small peritoneal metastases in HER2-expressing ovarian cancer. {sup 64}Cu-NOTA-pertuzumab is an effective PET tracer for the non-invasive imaging of HER2 expression in vivo, rendering it a potential tracer for treatment monitoring and improved patient stratification. (orig.)

  7. Role of immunoscintigraphy using Tc-99 m labelled monoclonal anti-CEA antibodies in the detection of Colorectal-rectal carcinoma

    International Nuclear Information System (INIS)

    Ziada, G.; Moustafa, H.; Elhaddad, Sh.; Elasser, M.

    1995-01-01

    Twelve patients with colorectal carcinoma confirmed histopathologically and associated with high serum CEA level and underwent preoperative immunoscintigraphy (planar and SPECT projections) followed by operative resection with able to detect the primary tumor in colorectal region with 100% sensitivity, specificity and accuracy. Immunoscintigraphy showed sensitivity of 85%, specificity of 60% and accuracy of 66.6% in detection of para-aortic lymph nodes involved, as compared to 0%, 25% and 25% in abdominal sonography respectively. Concerning the liver involvement, there was higher sensitivity of 100% and accuracy of 91% of immunoscintigraphy in comparison to 50% and 66.6% abdominal sonography respectively. Imaging procedure at 4 and 24 hors postinjection with planar and SPECT studies were useful for proper localization of involved sites and to differentiate between malignant and benign lesions. Immunoscintigraphy is a safe procedure and the preparation of the kit of monoclonal anti-CEA anti-body is rapid with labelling efficiency more than 95% and with no adverse reaction. 3 figs.,2 tabs

  8. Role of immunoscintigraphy using Tc-99 m labelled monoclonal anti-CEA antibodies in the detection of Colorectal-rectal carcinoma

    Energy Technology Data Exchange (ETDEWEB)

    Ziada, G; Moustafa, H; Elhaddad, Sh; Elasser, M [Center of oncology and nuclear medicine of Kasr El-Eini Hospital, Cairo university, (Egypt)

    1995-10-01

    Twelve patients with colorectal carcinoma confirmed histopathologically and associated with high serum CEA level and underwent preoperative immunoscintigraphy (planar and SPECT projections) followed by operative resection with able to detect the primary tumor in colorectal region with 100% sensitivity, specificity and accuracy. Immunoscintigraphy showed sensitivity of 85%, specificity of 60% and accuracy of 66.6% in detection of para-aortic lymph nodes involved, as compared to 0%, 25% and 25% in abdominal sonography respectively. Concerning the liver involvement, there was higher sensitivity of 100% and accuracy of 91% of immunoscintigraphy in comparison to 50% and 66.6% abdominal sonography respectively. Imaging procedure at 4 and 24 hors postinjection with planar and SPECT studies were useful for proper localization of involved sites and to differentiate between malignant and benign lesions. Immunoscintigraphy is a safe procedure and the preparation of the kit of monoclonal anti-CEA anti-body is rapid with labelling efficiency more than 95% and with no adverse reaction. 3 figs.,2 tabs.

  9. 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.

  10. 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

  11. Radiolabeled, nonspecific, polyclonal human immunoglobulin in the detection of focal inflammation by scintigraphy: Comparison with gallium-67 citrate and technetium-99m-labeled albumin

    International Nuclear Information System (INIS)

    Rubin, R.H.; Fischman, A.J.; Needleman, M.; Wilkinson, R.; Callahan, R.J.; Khaw, B.A.; Hansen, W.P.; Kramer, P.B.; Strauss, H.W.

    1989-01-01

    The accumulation of nonspecific polyclonal human immunoglobulin (IgG) radiolabeled with 125 I or 111 In was compared to that of [ 67 Ga]citrate and [ 99m Tc]albumin in rats with deep thigh inflammation due to Escherichia coli infection. Serial scintigrams were acquired at 1, 3, 24, and in some cases, 48 hr after injection. As early as 3 hr postinjection, [ 111 In]IgG showed greater accumulation at the lesion than [ 99m Tc]HSA (p less than 0.01). Both [ 125 I]IgG and [ 111 In]IgG showed greater accumulation than [ 67 Ga]citrate (p less than 0.01). At 24 hr, IgG image definition increased, while HSA image definition decreased, and the intensity of accumulation of both IgG preparations was greater than that of [ 67 Ga]citrate or [ 99m Tc]HSA (p less than 0.01). At all imaging times, [ 67 Ga]citrate accumulation was surprisingly low. In inflammation produced by Pseudomonas aeruginosa, Staphylococcus aureus, Klebsiella pneumoniae, Candida albicans, or turpentine, [ 111 In]IgG accumulation was similar to the results obtained with Escherichia coli. These studies suggest that focal sites of inflammation can be detected with radiolabeled nonspecific human polyclonal IgG

  12. 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)

  13. Interim report on intrathoracic radiotherapy of human small-cell lung carcinoma in nude mice with Re-188-RC-160, a radiolabeled somatostatin analogue

    International Nuclear Information System (INIS)

    Zamora, P.O.; Bender, H.; Biersack, H.J.; Knapp, F.F. Jr.

    1995-01-01

    The purpose of this study was to evaluate the therapeutic efficacy of Re-188-RC-160 in experimental models of human small cell lung carcinomas which mimic the clinical presentation. In the experimental model, cells from the human small cell lung carcinoma cell line NCI-H69 cells were inoculated into the thoracic cavity of athymic mice and rats. Subsequently, the biodistribution of Re-188-RC-160 after injection into the pleural cavity, a radiolabeled somatostatin analogue, was monitored as was the effect on the subsequent growth of tumors. The results presented here, and which are a part of a larger series of studies, suggest that Re-188-RC-160 can be effectively used in this animal model to restrict the growth of small cell lung carcinoma in the thoracic cavity

  14. 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)

  15. Radiolabeled annexin V for imaging apoptosis in radiated human follicular thyroid carcinomas - is an individualized protocol necessary?

    Energy Technology Data Exchange (ETDEWEB)

    Grosse, Jirka [Department of Nuclear Medicine, University of Regensburg, 93042 Regensburg (Germany); Department of Clinical Pharmacology and Toxicology, Charite-Universitaetsmedizin Berlin, Campus Benjamin Franklin, 14195 Berlin (Germany)], E-mail: jirka.grosse@klinik.uni-regensburg.de; Grimm, Daniela [Department of Clinical Pharmacology and Toxicology, Charite-Universitaetsmedizin Berlin, Campus Benjamin Franklin, 14195 Berlin (Germany); Department of Pharmacology, University of Aarhus, 8000 Aarhus (Denmark); Westphal, Kriss; Ulbrich, Claudia [Department of Clinical Pharmacology and Toxicology, Charite-Universitaetsmedizin Berlin, Campus Benjamin Franklin, 14195 Berlin (Germany); Moosbauer, Jutta [Department of Nuclear Medicine, University of Regensburg, 93042 Regensburg (Germany); Pohl, Fabian; Koelbl, Oliver [Department of Radiooncology, University of Regensburg, 93042 Regensburg (Germany); Infanger, Manfred [Department of Reconstructive Surgery, Charite-Universitaetsmedizin Berlin, Campus Benjamin Franklin, 12203 Berlin (Germany); Eilles, Christoph; Schoenberger, Johann [Department of Nuclear Medicine, University of Regensburg, 93042 Regensburg (Germany)

    2009-01-15

    Introduction: Induction of apoptosis is a widely used strategy for cancer therapy, but evaluating the degree and success of this therapy still poses a problem. Radiolabeled annexin V has been proposed to be a promising candidate for detecting apoptotic cells in tumors following chemotherapy in vivo. In order to see whether radiolabeled annexin V could be a suitable substance for the noninvasive in vivo detection of apoptosis in thyroid tissue and to establish an optimized study protocol, we investigated two poorly differentiated thyroid carcinoma cell lines: ML-1 and FTC-133. Methods: Apoptosis was evaluated before as well as 2 and 4 days after in vitro irradiation with 30 Gy X-rays. In this study, binding of FITC- and of {sup 125}I-labeled annexin V was measured in comparison to other apoptosis markers such as Bax, caspase-3 and Fas, which were determined by flow cytometry and Western blot analysis with densitometric evaluation. Results: ML-1 and FTC-133 cells showed a significant increase in annexin V binding 48 h after irradiation. Ninety-six hours after irradiation, the annexin V absorption capability of ML-1 cells was still maximal, while the living fraction of FTC-133 increased significantly. The amount of caspase-3 and Bax was clearly increased 48 h after irradiation and had normalized after 96 h in both cell lines. Fas protein concentrations remained unchanged in ML-1 cells but were significantly enhanced in FTC-133 cells. Conclusion: The binding of FITC- and {sup 125}I-labeled annexin V showed a significant accordance. A reliable evaluation of apoptosis induced by radiotherapy in thyroid tumors was possible 48 h after irradiation, when binding of radiolabeled annexin V is most significantly enhanced. Using two poorly differentiated cell lines of thyroid carcinoma, one may expect to find a nearly similar response to external irradiation. In contrast, the cell lines showed a completely contrary response. However, an individualized study protocol for each

  16. A simple in vitro method of radiolabelling human erythrocytes in whole blood with 113mIn-tropolonate

    International Nuclear Information System (INIS)

    Osman, S.; Danpure, H.J.

    1987-01-01

    A simple and rapid in vitro procedure has been developed for selectively radiolabelling erythrocytes in whole blood using 113m In-tropolonate. A maximum labelling efficiency of 97% was achieved, of which 95.5% was on the erythrocytes after only 5 min incubation of whole blodd at room temperature. The optimum amount of tropolone for labelling whole blood was 10 μg of tropolone per ml of blood using acid-citrate dextrose (ACD) as the anticoagulant and 50 μg of tropolone per ml of blood using heparin. Under these optimim conditions, only 2.5% of the cell-bound 113m In was released from the labelled cells during a 1 h in vitro incubation in cell-free plasma, irrespective of the anticoagulant used. These results suggest that 113m In-tropolonate may prove to be useful in vitro agent for labelling erythrocytes for short-term clinical investigations, especially at centres where 99m Tc and 111 In are unavailable. (author)

  17. 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)

  18. 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)

  19. 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

  20. 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

  1. Pharmacokinetics of the FO23C5 anti-CEA antibody fragment labelled with 99Tcm and 111In: a comparison in patients

    International Nuclear Information System (INIS)

    Hnatowich, D.J.; Mardirossian, G.; Rusckowski, M.; Roy, S.; Busche, H.; Griffin, T.W.; Brill, A.B.

    1993-01-01

    The FO23C5 anti-carcinoembryonic antigen (CEA) F(ab') 2 antibody was radiolabelled with sup(111)In via diethylenetriaminepentaacetic acid (DTPA) and directly with 99 Tc m by stannous ion and mercaptoethanol antibody reduction to compare the pharmacokinetics of these three agents. Four patients received 15 mCi 99 Tc m -Fab' 1 week before receiving 1 mCi 111 In-F(ab') 2 . Five additional patients received only the 99 Tc m -Fab'. The biodistribution of 99 Tc m was as expected for a labelled Fab' fragment: relative to 111 In, 99 Tc m cleared rapidly from circulation and into kidneys and urine. Liver levels of 111 In and 99 Tc m were surprisingly similar at 1 day although initial 111 In levels were lower and increased while 99 Tc m levels were higher and decreased. Spleen levels were also similar. In 4/9 patients receiving 99 Tc m , hepatobiliary clearance was observed at levels which could confuse interpretation whereas this mode of clearance was observed in only 1/4 patients receiving 111 In. Image quality was superior with 111 In versus 99 Tc m at 1 day postadministration as judged by counting rates and background activity whereas the opposite was true at 2-3 h postadministration. (author)

  2. Value of the radiolabelled GLP-1 receptor antagonist exendin(9-39) for targeting of GLP-1 receptor-expressing pancreatic tissues in mice and humans

    International Nuclear Information System (INIS)

    Waser, Beatrice; Reubi, Jean Claude

    2011-01-01

    Radiolabelled glucagon-like peptide 1 (GLP-1) receptor agonists have recently been shown to successfully image benign insulinomas in patients. Moreover, it was recently reported that antagonist tracers were superior to agonist tracers for somatostatin and gastrin-releasing peptide receptor targeting of tumours. The present preclinical study determines therefore the value of an established GLP-1 receptor antagonist for the in vitro visualization of GLP-1 receptor-expressing tissues in mice and humans. Receptor autoradiography studies with 125 I-GLP-1(7-36)amide agonist or 125 I-Bolton-Hunter-exendin(9-39) antagonist radioligands were performed in mice pancreas and insulinomas as well as in human insulinomas; competition experiments were performed in the presence of increasing concentration of GLP-1(7-36)amide or exendin(9-39). The antagonist 125 I-Bolton-Hunter-exendin(9-39) labels mouse pancreatic β-cells and mouse insulinomas, but it does not label human pancreatic β-cells and insulinomas. High affinity displacement (IC 50 approximately 2 nM) is observed in mouse β-cells and insulinomas with either the exendin(9-39) antagonist or GLP-1(7-36)amide agonist. For comparison, the agonist 125 I-GLP-1(7-36)amide intensively labels mouse pancreatic β-cells, mouse insulinoma and human insulinomas; high affinity displacement is observed for the GLP-1(7-36)amide in all tissues; however, a 5 and 20 times lower affinity is found for exendin(9-39) in the mouse and human tissues, respectively. This study reports a species-dependent behaviour of the GLP-1 receptor antagonist exendin(9-39) that can optimally target GLP-1 receptors in mice but not in human tissue. Due to its overly low binding affinity, this antagonist is an inadequate targeting agent for human GLP-1 receptor-expressing tissues, as opposed to the GLP-1 receptor agonist, GLP-1(7-36)amide. (orig.)

  3. Value of the radiolabelled GLP-1 receptor antagonist exendin(9-39) for targeting of GLP-1 receptor-expressing pancreatic tissues in mice and humans

    Energy Technology Data Exchange (ETDEWEB)

    Waser, Beatrice; Reubi, Jean Claude [University of Berne, Division of Cell Biology and Experimental Cancer Research, Institute of Pathology, P.O. Box 62, Bern (Switzerland)

    2011-06-15

    Radiolabelled glucagon-like peptide 1 (GLP-1) receptor agonists have recently been shown to successfully image benign insulinomas in patients. Moreover, it was recently reported that antagonist tracers were superior to agonist tracers for somatostatin and gastrin-releasing peptide receptor targeting of tumours. The present preclinical study determines therefore the value of an established GLP-1 receptor antagonist for the in vitro visualization of GLP-1 receptor-expressing tissues in mice and humans. Receptor autoradiography studies with {sup 125}I-GLP-1(7-36)amide agonist or {sup 125}I-Bolton-Hunter-exendin(9-39) antagonist radioligands were performed in mice pancreas and insulinomas as well as in human insulinomas; competition experiments were performed in the presence of increasing concentration of GLP-1(7-36)amide or exendin(9-39). The antagonist {sup 125}I-Bolton-Hunter-exendin(9-39) labels mouse pancreatic {beta}-cells and mouse insulinomas, but it does not label human pancreatic {beta}-cells and insulinomas. High affinity displacement (IC{sub 50} approximately 2 nM) is observed in mouse {beta}-cells and insulinomas with either the exendin(9-39) antagonist or GLP-1(7-36)amide agonist. For comparison, the agonist {sup 125}I-GLP-1(7-36)amide intensively labels mouse pancreatic {beta}-cells, mouse insulinoma and human insulinomas; high affinity displacement is observed for the GLP-1(7-36)amide in all tissues; however, a 5 and 20 times lower affinity is found for exendin(9-39) in the mouse and human tissues, respectively. This study reports a species-dependent behaviour of the GLP-1 receptor antagonist exendin(9-39) that can optimally target GLP-1 receptors in mice but not in human tissue. Due to its overly low binding affinity, this antagonist is an inadequate targeting agent for human GLP-1 receptor-expressing tissues, as opposed to the GLP-1 receptor agonist, GLP-1(7-36)amide. (orig.)

  4. 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)

  5. 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

  6. 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

  7. Human plasma concentrations of tolbutamide and acetaminophen extrapolated from in vivo animal pharmacokinetics using in vitro human hepatic clearances and simple physiologically based pharmacokinetic modeling for radio-labeled microdose clinical studies

    International Nuclear Information System (INIS)

    Yamazaki, Hiroshi; Kunikane, Eriko; Nishiyama, Sayako; Murayama, Norie; Shimizu, Makiko; Sugiyama, Yuichi; Chiba, Koji; Ikeda, Toshihiko

    2015-01-01

    The aim of the current study was to extrapolate the pharmacokinetics of drug substances orally administered in humans from rat pharmacokinetic data using tolbutamide and acetaminophen as model compounds. Adjusted animal biomonitoring equivalents from rat studies based on reported plasma concentrations were scaled to human biomonitoring equivalents using known species allometric scaling factors. In this extrapolation, in vitro metabolic clearance data were obtained using liver preparations. Rates of tolbutamide elimination were roughly similar in rat and human liver microsome experiments, but acetaminophen elimination by rat liver microsomes and cytosolic preparations showed a tendency to be faster than those in humans. Using a simple physiologically based pharmacokinetic (PBPK) model, estimated human plasma concentrations of tolbutamide and acetaminophen were consistent with reported concentrations. Tolbutamide cleared in a roughly similar manner in humans and rats, but medical-dose levels of acetaminophen cleared (dependent on liver metabolism) more slowly from plasma in humans than it did in rats. The data presented here illustrate how pharmacokinetic data in combination with a simple PBPK model can be used to assist evaluations of the pharmacological/toxicological potential of new drug substances and for estimating human radiation exposures from radio-labeled drugs when planning human studies. (author)

  8. Gene expression levels of matrix metalloproteinases in human atherosclerotic plaques and evaluation of radiolabeled inhibitors as imaging agents for plaque vulnerability

    International Nuclear Information System (INIS)

    Müller, Adrienne; Krämer, Stefanie D.; Meletta, Romana; Beck, Katharina; Selivanova, Svetlana V.; Rancic, Zoran; Kaufmann, Philipp A.; Vos, Bernhard; Meding, Jörg; Stellfeld, Timo; Heinrich, Tobias K.; Bauser, Marcus; Hütter, Joachim; Dinkelborg, Ludger M.; Schibli, Roger; Ametamey, Simon M.

    2014-01-01

    Introduction: Atherosclerotic plaque rupture is the primary cause for myocardial infarction and stroke. During plaque progression macrophages and mast cells secrete matrix-degrading proteolytic enzymes, such as matrix metalloproteinases (MMPs). We studied levels of MMPs and tissue inhibitor of metalloproteinases-3 (TIMP-3) in relation to the characteristics of carotid plaques. We evaluated in vitro two radiolabeled probes targeting active MMPs towards non-invasive imaging of rupture-prone plaques. Methods: Human carotid plaques obtained from endarterectomy were classified into stable and vulnerable by visual and histological analysis. MMP-1, MMP-2, MMP-8, MMP-9, MMP-10, MMP-12, MMP-14, TIMP-3, and CD68 levels were investigated by quantitative polymerase chain reaction. Immunohistochemistry was used to localize MMP-2 and MMP-9 with respect to CD68-expressing macrophages. Western blotting was applied to detect their active forms. A fluorine-18-labeled MMP-2/MMP-9 inhibitor and a tritiated selective MMP-9 inhibitor were evaluated by in vitro autoradiography as potential lead structures for non-invasive imaging. Results: Gene expression levels of all MMPs and CD68 were elevated in plaques. MMP-1, MMP-9, MMP-12 and MMP-14 were significantly higher in vulnerable than stable plaques. TIMP-3 expression was highest in stable and low in vulnerable plaques. Immunohistochemistry revealed intensive staining of MMP-9 in vulnerable plaques. Western blotting confirmed presence of the active form in plaque lysates. In vitro autoradiography showed binding of both inhibitors to stable and vulnerable plaques. Conclusions: MMPs differed in their expression patterns among plaque phenotypes, providing possible imaging targets. The two tested MMP-2/MMP-9 and MMP-9 inhibitors may be useful to detect atherosclerotic plaques, but not the vulnerable lesions selectively

  9. Fluorescent and radiolabelling of pepsin-digested human glomerular basement membrane with a newly developed hydroxy-coumarin derivative (CASE)

    International Nuclear Information System (INIS)

    Rand-Weaver, M.; Abuknesha, R.A.; Price, R.G.

    1985-01-01

    The labelling of pepsin-digested human glomerular basement membrane (pHGBM) with a newly developed fluorescent iodine acceptor 7-hydroxy-coumarin-3-acetic acid N-hydroxysucciniimydyl ester (CASE) is described. The binding of a monoclonal antibody to pHGBM was assessed by radiobinding assays, and when directly iodinated pHGBM was used there was no apparent binding. When CASE was conjugated to pHGBM prior to iodination 11% binding was achieved. CASE acting as an iodine acceptor may be useful for proteins containing few or inaccessible tyrosine residues or which are destroyed by introduction of 125 I. Since CASE is fluorescent, small amounts of material can be detected during isolation prior to iodination. (orig.)

  10. Localization by whole-body autoradiography of intact and fragmented radiolabeled antibodies in a metastatic human colonic cancer model

    International Nuclear Information System (INIS)

    Fand, Irwin; Sharkey, R.M.; Grundy, J.P.; Goldenberg, D.M.

    1992-01-01

    In this report, we have employed macroautoradiography to compare the tumor targeting of 125 I-labeled anti-carcinoembryonic antigen (CEA) MAb (NP-4) to 125 I-labeled anti-colon-specific antigen-p (CSAp) MAb (Mu-9) and their labeled F(ab') 2 and Fab' fragments, in nude mice each bearing large dorsal human colonic tumor xenografts, and small nodular tumors in the liver and lungs. Using intact MAbs (NP-4 and Mu-9), clearance of background radioactivity was delayed to 3-7 days post-treatment. Treatment with F(ab') 2 and Fab' fragments of both NP-4 and Mu-9 MAbs, however, promoted clearance of background 125 I-radioactivity which was well advanced by 6-24 h and complete by 24-48 h after injection. Localization of 125 I-radioactivity in large and micrometastatic tumor perimeters was the most characteristic uptake pattern observed for both intact and fragmented MAbs. Qualitative analysis of macroautoradiographic images and quantitative densitometry indicated that the higher tumor-to-blood ratios achieved with labeled F(ab') 2 and Fab' fragments at early time points, compared to labeled whole immunoglobulin, appeared to be more a function of rapid plasma clearance, tumor mass, location of xenografts and specific tumor growth patterns than increased tumor penetrance by lower molecular weight univalent and bivalent immune fragments. (Author)

  11. 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.)

  12. Characterization and uptake of radiolabelled meta-iodobenzylguanidine (MIBG) in a human neuroblastoma heterotransplant model in athymic rats

    International Nuclear Information System (INIS)

    Nilsson, S.; Paahlman, S.; Arnberg, H.; Letocha, H.; Westlin, J.E.

    1993-01-01

    Cells from an established human neuroblastoma cell line, SH-SY5Y, were demonstrated to grow and form solid tumours in nude rats. This cell line, which is an adrenergic subclone of the SK-N-SH cell line, has previously been used in differentiation model studies. The tumours retained the neuronal phenotype of the cultured cells, as evidenced by the expression of neuron-specific enolase (NSE) and chromogranin A + B. The transcription factor Isl-1, a protein expressed in subsets of neurons and endocrine cells as well as in neuroblastoma cells, was also expressed in the transplanted tumours, thus further verifying the retained phenotype of the cells under in vivo conditions. At scintigraphy utilizing 123 I-MIBG the optimal tumour/background ratio was obtained 20 h after injection. The assessment of tissue/serum ratios showed the highest uptake in the spleen (0.067% per gram of inj. activity), neuroblastoma tumours (0.067% per gram of inj. activity) and in the adrenals (0.065% per gram of inj. activity). (orig.)

  13. Characterization and uptake of radiolabelled meta-iodobenzylguanidine (MIBG) in a human neuroblastoma heterotransplant model in athymic rats

    Energy Technology Data Exchange (ETDEWEB)

    Nilsson, S. (Dept. of Oncology, Univ. Hospital, Uppsala (Sweden)); Paahlman, S. (Dept. of Pathology, Univ. Hospital, Uppsala (Sweden)); Arnberg, H. (Dept. of Oncology, Univ. Hospital, Uppsala (Sweden)); Letocha, H. (Dept. of Oncology, Univ. Hospital, Uppsala (Sweden)); Westlin, J.E. (Dept. of Oncology, Univ. Hospital, Uppsala (Sweden))

    1993-01-01

    Cells from an established human neuroblastoma cell line, SH-SY5Y, were demonstrated to grow and form solid tumours in nude rats. This cell line, which is an adrenergic subclone of the SK-N-SH cell line, has previously been used in differentiation model studies. The tumours retained the neuronal phenotype of the cultured cells, as evidenced by the expression of neuron-specific enolase (NSE) and chromogranin A + B. The transcription factor Isl-1, a protein expressed in subsets of neurons and endocrine cells as well as in neuroblastoma cells, was also expressed in the transplanted tumours, thus further verifying the retained phenotype of the cells under in vivo conditions. At scintigraphy utilizing [sup 123]I-MIBG the optimal tumour/background ratio was obtained 20 h after injection. The assessment of tissue/serum ratios showed the highest uptake in the spleen (0.067% per gram of inj. activity), neuroblastoma tumours (0.067% per gram of inj. activity) and in the adrenals (0.065% per gram of inj. activity). (orig.).

  14. 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)

  15. Fully human IgG and IgM antibodies directed against the carcinoembryonic antigen (CEA Gold 4 epitope and designed for radioimmunotherapy (RIT of colorectal cancers

    Directory of Open Access Journals (Sweden)

    Pugnière Martine

    2004-10-01

    Full Text Available Abstract Background Human monoclonal antibodies (MAbs are needed for colon cancer radioimmunotherapy (RIT to allow for repeated injections. Carcinoembryonic antigen (CEA being the reference antigen for immunotargeting of these tumors, we developed human anti-CEA MAbs. Methods XenoMouse®-G2 animals were immunized with CEA. Among all the antibodies produced, two of them, VG-IgG2κ and VG-IgM, were selected for characterization in vitro in comparison with the human-mouse chimeric anti-CEA MAb X4 using flow cytometry, surface plasmon resonance, and binding to radiolabeled soluble CEA and in vivo in human colon carcinoma LS174T bearing nude mice. Results Flow cytometry analysis demonstrated binding of MAbs on CEA-expressing cells without any binding on NCA-expressing human granulocytes. In a competitive binding assay using five reference MAbs, directed against the five Gold CEA epitopes, VG-IgG2κ and VG-IgM were shown to be directed against the Gold 4 epitope. The affinities of purified VG-IgG2κ and VG-IgM were determined to be 0.19 ± 0.06 × 108 M-1 and 1.30 ± 0.06 × 108 M-1, respectively, as compared with 0.61 ± 0.05 × 108 M-1 for the reference MAb X4. In a soluble phase assay, the binding capacities of VG-IgG2κ and VG-IgM to soluble CEA were clearly lower than that of the control chimeric MAb X4. A human MAb concentration of about 10-7 M was needed to precipitate approximatively 1 ng 125I-rhCEA as compared with 10-9 M for MAb X4, suggesting a preferential binding of the human MAbs to solid phase CEA. In vivo, 24 h post-injection, 125I-VG-IgG2κ demonstrated a high tumor uptake (25.4 ± 7.3%ID/g, close to that of 131I-X4 (21.7 ± 7.2%ID/g. At 72 h post-injection, 125I-VG-IgG2κ was still concentrated in the tumor (28.4 ± 11.0%ID/g whereas the tumor concentration of 131I-X4 was significantly reduced (12.5 ± 4.8%ID/g. At no time after injection was there any accumulation of the radiolabeled MAbs in normal tissues. A pertinent analysis of

  16. 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

  17. Comparison of in-vivo kinetics of an antibody cocktail containing 131-iodine anti-CA-19/9 and 131-iodine anti-CEA with 111-indium labelled monoclonal anti-CA-19/9 using a tumor model in mice

    International Nuclear Information System (INIS)

    Koenig, S.; Orth, M.; Henze, E.

    1993-01-01

    In this study the potential diagnostic value of an 111-In-labelled CA-19/9-F (ab)-fragment was compared to that of an antibody cocktail of 131-iodine-labelled CA-19/9 and 131-iodine-labelled anti-CEA for identification of pancreas cancer by a nude mice model. 111-In-labelled CA-19/9 and the 131-iodine antibody cocktail were injected into 35 nude mice xenotransplantated with human pancreas cancer. Scintigrams were obtained and the relative distribution of activity in tumor and in several organs were determined by ROI-technique. These values were compared with the in vitro results of organ measurement after dissection of nude mice. Blood pool of 131-iodine-labelled antibodies showed only a nuclide accumulation in the thyroid because of very high rate of dejodination and missing blockade of thyroid. Other organs were not detectabel in scintigraphy because of high nucleotide accumulation of thyroid. The tumor-to-blood-ratio of organ-measurements was 18±4.3, kidneys-background-ratio 2.1±7.3, liver-background-ratio 5.8±2.0. These results are similar to those of 111-In-labelled fragments. Thus it is established that antibody cocktail had no essential advantage over singular antibody in mouse model. It gives a good tumor contrast with tumor-background-quotient of 15±7.4 measured by scintigraphy and tumor background-quotient 18±4.3 in-vitro-organ-measurement. (orig.) [de

  18. 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.

  19. 99mTc human IgG radiolabelled by HYNIC. Biodistribution and scintigraphy of experimentally induced inflammatory lesions in animal model

    International Nuclear Information System (INIS)

    Karczmarczyk, U.; Markiewicz, A.; Mikolajczak, R.; Michalik, J.; Lisiak, E.; Bilski, M.; Pietrzykowski, J.

    2004-01-01

    Our goal was the efficient labelling of highly purified human gammaglobulin. This radioactive protein fraction can be used as a basic compound of radiopharmaceutical formulation for inflammation lesion diagnosis. This application was experimentally illustrated in animal models with artificially induced inflammatory lesions after turpentine oil injection into mouse leg muscle. Hydrazine nicotinamine derivative of human gammaglobulin (IgG-HYNIC) was synthesized according to Abrams method. The radionuclide: technetium 99mT c has been introduced into protein molecules by indirect method incorporation in phosphate buffer, pH 7.4, in the presence of stannous chloride as a reducing agent for sodium pertechnetate, and EDTA as a coligand. Radiochemical purity was estimated by thin layer chromatography. The stability of labelled IgG-HYNIC derivative in human serum in presence of copper, cobalt, iron and manganese salts was analyzed by HPLC method (BioSEP SEC 4000, eluent: 0.1mol/L phosphate). Inflammation lesions were induced in Balb/3 mice muscles by injection of 0.2 ml turpentine oil into the leg muscle. Five days later, inflammation lesions were visualized by hIgG-HYNIC- 99mT c injections. The tracer accumulation in tissue was evaluated by gamma camera at 1 to 24 hour intervals. Efficiency of technetium 99mT c human gammaglobulin labelling (pH 7.4, temp. 37 o C) was strictly dependant on ligand and coligand presence in the reaction mixture. Labelling of IgG molecules without any supplements resulted in very low efficiency, never exceeding the range of 5%. Presence of EDTA or hydrazine nicotinamide (HYNIC) conjugated with IgG increased radiolabelling efficiency to 50%. IgG-HYNIC derivative in EDTA presence enables us to reach value above 95% radiochemical purity. Stability of IgG-HYNIC derivative labelled with technetium 99mT c decreased rapidly in serum in time - up to 70% of initial value in 30 minutes and only 20% during further 4 hr incubation. This means that as much

  20. 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

  1. Two-dimensional analysis of metabolically and cell surface radiolabeled proteins of some human lymphoid and myeloid leukemia cell lines. II. Glycosylated and phosphorylated proteins

    Energy Technology Data Exchange (ETDEWEB)

    Chorvath, B; Duraj, J; Sedlak, J; Pleskova, I

    1986-01-01

    Cell surface glycoproteins, radiolabelled by the sodium metaperiodate/tritiated borohydride technique, and cell phosphoproteins, metabolically radiolabelled with /sup 32/P-orthophosphate were analyzed by two-dimensional electrophoretic analysis in some myeloid and lymphoid leukemia cell lines. Some markedly expressed major glycoproteins were predominant in some of the cell lines (such as 95k and 100k glycoproteins with marked charge heterogeneity in non-T, non-B acute lymphoblastic leukemia cell lines NALM 6 and NALM 16), but markedly quantitatively reduced in other examined cell lines, such as lymphoblastoid cell line UHKT 34/2. /sup 32/P-orthophosphate radiolabelled phosphoprotein two-dimensional patterns of the examined lymphoid leukemia cell lines were essentially similar, with some minor differences, in examined lymphoid and myeloid leukemia cell lines, such as marked expression of a series of large phosphoproteins in the molecular weight range 80-100k in lymphoid cell lines and almost complete absence of these phosphoproteins on the examined myeloid leukemia cell lines. Another configuration of acidic phosphoproteins (30-35k) exhibited individual cell line variability and differences between both individual myeloid leukemia cell lines and between the lymphoid and myeloid cell lines examined. (author) 2 figs., 15 refs.

  2. 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

  3. 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.

  4. 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)

  5. 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.)

  6. Comparative imaging and biodistribution studies with an anti-CEA monoclonal antibody and its F(ab)2 and Fab fragments in mice with colon carcinoma xenografts

    International Nuclear Information System (INIS)

    Andrew, S.M.; Pimm, M.V.; Baldwin, R.W.; Perkins, A.C.

    1986-01-01

    An IgG1 mouse monoclonal antibody directed against CEA has been digested with papain to yield F(ab) 2 and Fab fragments. Following radioiodination, intact antibody and fragments showed specific binding to cells of a CEA-producing tumour, although the immune reactivities of the fragments were lower than that of intact antibody. Gamma scintigraphy of nude mice bearing CEA producing human tumour xenografts and injected with 131 I-labelled fragments showed earlier and superior imaging of tumours than did 131 I-intact antibody, and this was most marked with the Fab fragment. Sequential dissection analyses showed that this was due to earlier and higher tumour-to-blood ratios with fragments than with intact antibody, but in absolute terms the degree of localization of both fragment types was significantly lower than that of intact antibody. (orig.)

  7. Comparison between anti-CEA and anti-HER2 212Pb-labeled mAbs during α-RIT of small volume peritoneal carcinomatosis - Role of activity distribution on therapeutic efficacy and toxicity?

    International Nuclear Information System (INIS)

    Elgqvist, J.; Boudousq, V.; Bobyk, L.; Busson, M.; Lozza, C.; Navarro-Teulon, I.; Pouget, J.P.; Maquaire, P.; Torgue, J.

    2015-01-01

    Full text of publication follows. Objectives: we investigated the role of internalizing/non-internalizing monoclonal antibodies (mAbs) on the final outcome (efficacy/toxicity) of mice treated with alpha radioimmunotherapy (α- RIT) using 212 Pb-labeled mAbs. The relationship between distribution of radioactivity at the tissue level and biological parameters was also assessed. Methods: nude mice bearing 2-3 mm peritoneal nodules obtained by xenograft of A-431 tumor cells, expressing low and high level of HER2 and CEA receptors, respectively, were intraperitoneally (i.p.) injected with increasing activities (370-1480 kBq; 37 MBq/mg) of either 35A7 (non-internalising anti-CEA), Trastuzumab (internalizing anti-HER2) or PX (non-specific) 212 Pb-labeled mAbs. Control groups were injected with corresponding amount of unlabeled mAbs or with NaCl. Tumor growth was followed by bioluminescence and median survival (MS) of control and treated mice was determined. 212 Pb-35A7 and 212 Pb-Trastuzumab biodistribution was used to determine the cumulative uptake of radioactivity (UOR) in organs and tumors. Mean absorbed doses were calculated using the MIRD formalism. Haematological, liver and kidney toxicities were also assessed. Distribution of radioactivity at the tissue level was determined by digital micro-autoradiography and the relationship with biological markers of tissue damage was investigated using immunohistochemistry. Results: a mild and transient haematological toxicity in groups treated with the highest amount of activity was observed. MS of the groups treated either with internalizing or non-internalizing 212 Pb-labeled mAbs was significantly improved compared to those treated with non-specific 212 Pb-PX or those only given unlabeled mAbs or just NaCl. MS ranged from 42 days to 94 days using various activity levels of anti-CEA 212 Pb-35A7 while MS was not reached over the follow-up period of 130 days for mice treated with anti-HER2 212 Pb-Trastuzumab. However, UOR and

  8. Preparation of the metabotropic glutamate receptor 5 (mGluR5) PET tracer [18F]FPEB for human use: An automated radiosynthesis and a novel one-pot synthesis of its radiolabeling precursor

    International Nuclear Information System (INIS)

    Lim, Keunpoong; Labaree, David; Li, Songye; Huang, Yiyun

    2014-01-01

    The radiotracer 3-[ 18 F]fluoro-5-(2-pyridinylethynyl)benzonitrile, or [ 18 F]FPEB, is a promising PET imaging agent for the metabotropic glutamate subtype 5 receptor (mGluR5). In an effort to develop a routine production method of this radiotracer for use in clinical research we adapted its radiosynthesis to an automated chemistry module. In the meanwhile, we also developed a simplified “one-pot” method for the preparation of the nitrobenzonitrile radiolabeling precursor for [ 18 F]FPEB and its reference standard to replace the existing multi-step synthetic approach. - Highlights: • Radiosynthesis of [ 18 F]FPEB was performed in a Tracerlab FX-FN automated module. • The radiolabeling precursor was prepared from a “one-pot” Suzuki coupling method. • Total synthesis time from EOB to a final injectable dose was about 90 min. • The procedure was applied in the routine preparation of [ 18 F]FPEB for human use

  9. 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.)

  10. 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

  11. Positron Emission Tomography Imaging Using Radiolabeled Inorganic Nanomaterials

    Science.gov (United States)

    Sun, Xiaolian; Cai, Weibo; Chen, Xiaoyuan

    2015-01-01

    . Although being fast and specific, only a few combinations of isotopes and nanoparticles have been explored. Since the applications of radiolabeled nanoparticles are based on the premise that the radioisotopes are stably attached to the nanomaterials, stability (colloidal and radiochemical) assessment of radiolabeled nanoparticles is also highlighted. Despite the fact that thousands of nanomaterials have been developed for clinical research, only very few have moved to humans. One major reason is the lack of understanding of the biological behavior of nanomaterials. We discuss specific examples of using PET imaging to monitor the in vivo fate of radiolabeled nanoparticles, emphasizing the importance of labeling strategies and caution in interpreting PET data. Design considerations for radiolabeled nanoplatforms for multimodal molecular imaging are also illustrated, with a focus on strategies to combine the strengths of different imaging modalities and to prolong the circulation time. PMID:25635467

  12. 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

  13. 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)

  14. 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)

  15. 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

  16. Induction of Human Somatostatin Receptor Subtype 2 on Breast Tumors with an Adenoviral Vector for Their Treatment and Detection with a Radiolabeled Peptide

    National Research Council Canada - National Science Library

    Rogers, Buck

    2002-01-01

    .... An adenoviral vector encoding the human somatostatin receptor subtype 2 (AdSSTr2) has been produced. The MDA- MB-468 and BT-474 human breast cancer cells were infected with AdSSTr2 and harvested 48 h later for membrane preparations...

  17. Potent radiolabeled human renin inhibitor, [3H]SR42128: enzymatic, kinetic, and binding studies to renin and other aspartic proteases

    International Nuclear Information System (INIS)

    Cumin, F.; Nisato, D.; Gagnol, J.P.; Corvol, P.

    1987-01-01

    The in vitro binding of [ 3 H]SR42128 (Iva-Phe-Nle-Sta-Ala-Sta-Arg), a potent inhibitor of human renin activity, to purified human renin and a number of other aspartic proteases was examined. SR42128 was found to be a competitive inhibitor of human renin, with a K/sub i/ of 0.35 nM at pH 5.7 and 2.0 nM at pH 7.4; it was thus more effective at pH 5.7 than at pH 7.4. Scatchard analysis of the interaction binding of [ 3 H]SR42128 to human renin indicated that binding was reversible and saturable at both pH 5.7 and pH 7.4. There was a single class of binding sites, and the K/sub D/ was 0.9 nM at pH 5.7 and 1 nM at pH 7.4. The association rate was 10 times more rapid at pH 5.7 than at pH 7.4, but there was no difference between the rates of dissociation of the enzyme-inhibitor complex at the two pHs. The effect of pH on the binding of [ 3 H]SR42128 to human renin, cathepsin D, pepsin, and gastricsin was also examined over the pH range 3-8. All the aspartic proteases had a high affinity for the inhibitor at low pH. However, at pH 7.4, [ 3 H]SR42128 was bound only to human renin and to none of the other aspartic proteases. Competitive binding studies with [ 3 H]SR42128 and a number of other inhibitors on human renin or cathepsin D were used to examine the relationships between structure and activity in these systems. The study as a whole indicates that pH plays a major role in the binding of [ 3 H]SR42128 to aspartic proteases and that the nature of the inhibitor residue reacting with the renin S 2 subsites is of critical importance for the specificity of the renin-inhibitor interaction

  18. 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.''

  19. A human osteosarcoma cell line expressing herpes simplex type-1 thymidine kinase: studies with radiolabeled (E)-5-(2-iodovinyl)-2'-fluoro-2'-deoxyuridine

    International Nuclear Information System (INIS)

    Morin, Kevin W.; Duan Weili; Knaus, Edward E.; McEwan, Alexander J.B.; Wiebe, Leonard I.

    2005-01-01

    Introduction: (E)-5-(2-Iodovinyl)-2'-fluoro-2'-deoxyuridine (IVFRU) is a pyrimidine nucleoside analogue that accumulates selectively in murine cells expressing herpes simplex type-1 thymidine kinase (HSV-1 TK). The uptake of [ 125 I]IVFRU in human 143B osteosarcoma cells transduced with a retroviral vector bearing the HSV-1 TK gene (143B-LTK cells) is now reported. Methods: HSV-1 TK gene expression in 143B-LTK cells was confirmed by Western blotting and reverse transcriptase (RT)-PCR. Cell and subcellular uptake of [ 125 I]IVFRU was determined in cell culture, and whole body biodistribution after intravenous injection of [ 125 I]IVFRU was determined using nude mice bearing implanted 143B or 143B-LTK tumors. Results: Although IVFRU was less toxic to the human cell line expressing HSV-1 TK (143B-LTK) than ganciclovir, both IVFRU and ganciclovir were not toxic to the cell line not expressing HSV-1 TK (143B). When cells were exposed to [ 125 I]IVFRU in vitro, only the 143B-LTK cells accumulated radioactivity. The acid-soluble fraction from 143B-LTK cell lysates contained 8-fold greater activity than the acid-insoluble fraction after an 8-h exposure to [ 125 I]IVFRU. Biodistribution of [ 125 I]IVFRU in nude mice bearing subcutaneous 143B and 143B-LTK tumors revealed widespread distribution of the nucleoside in vivo but with specific localization in 143B-LTK tumors. Conclusion: The underlying biochemical process of metabolic entrapment of IVFRU in human osteosarcoma cells expressing HSV-1 TK is responsible for selective localization in these cells. The differences in subcellular distribution into the nucleic acid fraction, and in cytotoxicity, reflect the importance of cell type and lineage as determinants of the performance of gene imaging radiopharmaceuticals

  20. A human osteosarcoma cell line expressing herpes simplex type-1 thymidine kinase: studies with radiolabeled (E)-5-(2-iodovinyl)-2'-fluoro-2'-deoxyuridine

    Energy Technology Data Exchange (ETDEWEB)

    Morin, Kevin W. [Faculty of Pharmacy and Pharmaceutical Sciences, University of Alberta, Edmonton, T6G 2N8 (Canada); Duan Weili [Faculty of Pharmacy and Pharmaceutical Sciences, University of Alberta, Edmonton, T6G 2N8 (Canada); Knaus, Edward E. [Faculty of Pharmacy and Pharmaceutical Sciences, University of Alberta, Edmonton, T6G 2N8 (Canada); McEwan, Alexander J.B. [Department of Radiology and Diagnostic Imaging, Faculty of Medicine and Dentistry, University of Alberta, Edmonton, T6G 2N8 (Canada); Wiebe, Leonard I. [Faculty of Pharmacy and Pharmaceutical Sciences, University of Alberta, Edmonton, T6G 2N8 (Canada)]. E-mail: leonard.wiebe@ualberta.ca

    2005-07-01

    Introduction: (E)-5-(2-Iodovinyl)-2'-fluoro-2'-deoxyuridine (IVFRU) is a pyrimidine nucleoside analogue that accumulates selectively in murine cells expressing herpes simplex type-1 thymidine kinase (HSV-1 TK). The uptake of [{sup 125}I]IVFRU in human 143B osteosarcoma cells transduced with a retroviral vector bearing the HSV-1 TK gene (143B-LTK cells) is now reported. Methods: HSV-1 TK gene expression in 143B-LTK cells was confirmed by Western blotting and reverse transcriptase (RT)-PCR. Cell and subcellular uptake of [{sup 125}I]IVFRU was determined in cell culture, and whole body biodistribution after intravenous injection of [{sup 125}I]IVFRU was determined using nude mice bearing implanted 143B or 143B-LTK tumors. Results: Although IVFRU was less toxic to the human cell line expressing HSV-1 TK (143B-LTK) than ganciclovir, both IVFRU and ganciclovir were not toxic to the cell line not expressing HSV-1 TK (143B). When cells were exposed to [{sup 125}I]IVFRU in vitro, only the 143B-LTK cells accumulated radioactivity. The acid-soluble fraction from 143B-LTK cell lysates contained 8-fold greater activity than the acid-insoluble fraction after an 8-h exposure to [{sup 125}I]IVFRU. Biodistribution of [{sup 125}I]IVFRU in nude mice bearing subcutaneous 143B and 143B-LTK tumors revealed widespread distribution of the nucleoside in vivo but with specific localization in 143B-LTK tumors. Conclusion: The underlying biochemical process of metabolic entrapment of IVFRU in human osteosarcoma cells expressing HSV-1 TK is responsible for selective localization in these cells. The differences in subcellular distribution into the nucleic acid fraction, and in cytotoxicity, reflect the importance of cell type and lineage as determinants of the performance of gene imaging radiopharmaceuticals.

  1. 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.

  2. 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

  3. 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

  4. 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).

  5. Direct Comparison of Radiolabeled Probes FMAU, FHBG, and FHPG as PET Imaging Agents for HSV1-tk Expression in a Human Breast Cancer Model

    Directory of Open Access Journals (Sweden)

    Mian M. Alauddin

    2004-04-01

    Full Text Available 2′-Deoxy-2′-fluoro-5-methyl-1-β-d-arabinofuranosyluracil (FMAU, 9-(4-fluoro-3-hydroxy-methyl-butylguanine (FHBG and 9-[(3-fluoro-1-hydroxy-2-propoxymethyl]-guanine (FHPG have been evaluated in a human breast cancer model as potential radiotracers for PET imaging of HSV1-tk gene expression. In vitro accumulation of [14C]FMAU, [18F]FHBG, and [18F]FHPG in HSV1-tk-expressing cells was 14- to 16-fold (p < .001, 9- to 13-fold (p < .001, and 2- to 3-fold (p < .05 higher than tk-negative control cells, respectively, between 30 and 240 min. Accumulation of FMAU and FHBG in vector-transduced cells was 10- to 14-fold and 6- to 10-fold higher than wild-type cells, respectively. At 2 hr, uptake of [14C]FMAU in tk-positive cells was 6.3-fold and 60-fold higher than [18F]FHBG and [18F]FHPG, respectively. In vivo, tumor uptake of [14C]FMAU in HSV1-tk-expressing cells was 3.7-fold and 5.5-fold (p < .001 higher than tk-negative control cells at 1 and 2 hr, respectively. Tumor uptake of [18F]FHBG was 4.2-fold and 12.6-fold higher (p < .001 than tk-negative cells at the same time points. Incorporation of [14C]FMAU in tk-positive tumor was 18-fold and 24-fold higher (p < .001 than [18F]FHBG at 1 and 2 hr, respectively. Micro-PET images support the biodistribution results and indicate that both [18F]FMAU and [18F]FHBG are useful for imaging HSV1-tk expression in breast cancer. Although FMAU demonstrates higher total incorporation (%dose/g in tumor tissue compared with the other tracers, FHBG is superior in terms of specific accumulation in transfected cells at later time points.

  6. 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.

  7. 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)

  8. 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?

  9. 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.)

  10. 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.)

  11. 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)

  12. 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)

  13. Balanced secretion of anti-CEA x anti-CD3 diabody chains using the 2A self-cleaving peptide maximizes diabody assembly and tumor-specific cytotoxicity

    DEFF Research Database (Denmark)

    Mølgaard, Kasper; Compte, Marta; Alanes, Natalia Nuñez del Prado

    2017-01-01

    Adoptive transfer of genetically engineered human cells secreting bispecific T cell engagers has shown encouraging therapeutic effects in preclinical models of cancer. However, reducing the toxicity and improving the effectiveness of this emerging immunotherapeutic strategy will be critical to it...

  14. 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.

  15. 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.

  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. 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.

  18. 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)

  19. 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)

  20. Radioimmunoimaging of human colon carcinoma grafted into nudemice using 131I-labeled monoclonal anticea antibody and its F(ab')2 fragments

    International Nuclear Information System (INIS)

    Liu Guangda

    1988-01-01

    131 I-labeled monoclonal anti-CEA antibody and its F(ab') 2 fragments were injected into nude mice bearing human colon carcinoma xenografts for tumor localization and radioimmunoimaging studies. Transplanted tumors were visualized in 12 hours after injection of the labeled anti-CEA or its F(ab') 2 by gamma camera. Biodistribution data indicated that F(ab') 2 fragments were cleared more rapidly from blood (T 1/2 = 13.3 h for F(ab') 2 , T 1/2 = 21.1 h for intact antibody) over 6-24 h and had higher tumor blood ratios. The intact antibody was concentrated in the tumor better than F(ab') 2 . In double-label experiments, a nonspecific localization of the control ( 125 I-labeled anti-HCG) in the tumor was also observed

  1. 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.)

  2. 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

  3. 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

  4. 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

  5. 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.)

  6. 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).

  7. 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)

  8. 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.

  9. 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)

  10. 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)

  11. 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

  12. 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

  13. 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)

  14. 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

  15. 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,

  16. Highly efficient method for 125I-radiolabeling of biomolecules using inverse-electron-demand Diels-Alder reaction.

    Science.gov (United States)

    Choi, Mi Hee; Shim, Ha Eun; Yun, Seong-Jae; Kim, Hye Rim; Mushtaq, Sajid; Lee, Chang Heon; Park, Sang Hyun; Choi, Dae Seong; Lee, Dong-Eun; Byun, Eui-Baek; Jang, Beom-Su; Jeon, Jongho

    2016-04-19

    In this report, we present a rapid and highly efficient method for radioactive iodine labeling of trans-cyclooctene group conjugated biomolecules using inverse-electron-demand Diels-Alder reaction. Radioiodination reaction of the tetrazine structure was carried out using the stannylated precursor 2 to give 125 I-labeled azide ([ 125 I]1) with high radiochemical yield (65±8%) and radiochemical purity (>99%). For radiolabeling application of [ 125 I]1, trans-cyclooctene derived cRGD peptide and human serum albumin were prepared. These substrated were reacted with [ 125 I]1 under mild condition to provide the radiolabeled products [ 125 I]6 and [ 125 I]8, respectively, with excellent radiochemical yields. The biodistribution study of [ 125 I]8 in normal ICR mice showed significantly lower thyroid uptake values than that of 125 I-labeled human serum albumin prepared by a traditional radiolabeling method. Therefore [ 125 I]8 will be a useful radiolabeled tracer in various molecular imaging and biological studies. Those results clearly demonstrate that [ 125 I]1 will be used as a valuable prosthetic group for radiolabeling of biomolecules. Copyright © 2016 Elsevier Ltd. All rights reserved.

  17. 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

  18. 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

  19. 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.

  20. 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

  1. 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

  2. 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.

  3. 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

  4. 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.)

  5. 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.)

  6. 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.)

  7. 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)

  8. 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

  9. 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

  10. 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)

  11. 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.

  12. 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)

  13. Tumour uptake of the radiolabelled somatostatin analogue [DOTA0,TYR3]octreotide is dependent on the peptide amount

    International Nuclear Information System (INIS)

    Jong, M. de; Breeman, W.A.P.; Bernard, B.F.; Gameren, A. van; Bruin, E. de; Bakker, W.H.; Van der Pluijm, M.E.; Krenning, E.P.; Visser, T.J.; Maecke, H.R.

    1999-01-01

    . Our observations of mass-dependent differences in uptake of radiolabelled [DOTA 0 , Tyr 3 ]octreotide, being the resultant of a positive effect of increasing amounts of peptide on, for example, receptor clustering and a negative effect of receptor saturation, are of consequence for rat radionuclide therapy studies with radiolabelled peptides and may also be of consequence for human radionuclide therapy studies with this compound. (orig.)

  14. 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.)

  15. 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)

  16. 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

  17. 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.

  18. 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

  19. 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)

  20. 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.

  1. 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)

  2. 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).

  3. 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

  4. 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

  5. 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

  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. Radiolabeling of rituximab with 188Re and 99mTc using the tricarbonyl technology

    International Nuclear Information System (INIS)

    Dias, Carla Roberta; Jeger, Simone; Osso, Joao Alberto; Mueller, Cristina; De Pasquale, Christine; Hohn, Alexander; Waibel, Robert; Schibli, Roger

    2011-01-01

    Introduction: The most successful clinical studies of immunotherapy in patients with non-Hodgkin's lymphoma (NHL) use the antibody rituximab (RTX) targeting CD20 + B-cell tumors. Rituximab radiolabeled with β - emitters could potentiate the therapeutic efficacy of the antibody by virtue of the particle radiation. Here, we report on a direct radiolabeling approach of rituximab with the 99m Tc- and 188 Re-tricarbonyl core (IsoLink technology). Methods: The native format of the antibody (RTX wt ) as well as a reduced form (RTX red ) was labeled with 99m Tc/ 188 Re(CO) 3 . The partial reduction of the disulfide bonds to produce free sulfhydryl groups (-SH) was achieved with 2-mercaptoethanol. Radiolabeling efficiency, in vitro human plasma stability as well as transchelation toward cysteine and histidine was investigated. The immunoreactivity and binding affinity were determined on Ramos and/or Raji cells expressing CD20. Biodistribution was performed in mice bearing subcutaneous Ramos lymphoma xenografts. Results: The radiolabeling efficiency and kinetics of RTX red were superior to that of RTX wt ( 99m Tc: 98% after 3 h for RTX red vs. 70% after 24 h for RTX wt ). 99m Tc(CO) 3 -RTX red was used without purification for in vitro and in vivo studies whereas 188 Re(CO) 3 -RTX red was purified to eliminate free 188 Re-precursor. Both radioimmunoconjugates were stable in human plasma for 24 h at 37 o C. In contrast, displacement experiments with excess cysteine/histidine showed significant transchelation in the case of 99m Tc(CO) 3 -RTX red but not with pre-purified 188 Re(CO) 3 -RTX red . Both conjugates revealed high binding affinity to the CD20 antigen (K d =5-6 nM). Tumor uptake of 188 Re(CO) 3 -RTX red was 2.5 %ID/g and 0.8 %ID/g for 99m Tc(CO) 3 -RTX red 48 h after injection. The values for other organs and tissues were similar for both compounds, for example the tumor-to-blood and tumor-to-liver ratios were 0.4 and 0.3 for 99m Tc(CO) 3 -RTX red and for 188 Re

  8. 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

  9. Biodistribution of radiolabelled human dendritic cells injected by various routes

    International Nuclear Information System (INIS)

    Quillien, Veronique; Moisan, Annick; Carsin, Andre; Lesimple, Thierry; Lefeuvre, Claudia; Bertho, Nicolas; Devillers, Anne; Toujas, Louis; Adamski, Henri; Leberre, Claudine

    2005-01-01

    The purpose of this study was to investigate the biodistribution of mature dendritic cells (DCs) injected by various routes, during a cell therapy protocol. In the context of a vaccine therapy protocol for melanoma, DCs matured with Ribomunyl and interferon-gamma were labelled with 111 In-oxine and injected into eight patients along various routes: afferent lymphatic vessel (IL) (4 times), lymph node (IN) (5 times) and intradermally (ID) (6 times). Scintigraphic investigations showed that the IL route allowed localisation of 80% of injected radioactivity in eight to ten nodes. In three cases of IN injection, the entire radioactivity stagnated in the injected nodes, while in two cases, migration to adjacent nodes was observed. This migration was detected rapidly after injection, as with IL injections, suggesting that passive transport occurred along the physiological lymphatic pathways. In two of the six ID injections, 1-2% of injected radioactivity reached a proximal lymph node. Migration was detectable in the first hour, but increased considerably after 24 h, suggesting an active migration mechanism. In both of the aforementioned cases, DCs were strongly CCR7-positive, but this feature was not a sufficient condition for effective migration. In comparison with DCs matured with TNF-α, IL-1β, IL-6 and PGE2, our DCs showed a weaker in vitro migratory response to CCL21, despite comparable CCR7 expression, and higher allostimulatory and TH1 polarisation capacities. The IL route allowed reproducible administration of specified numbers of DCs. The IN route sometimes yielded fairly similar results, but not reproducibly. Lastly, we showed that DCs matured without PGE2 that have in vitro TH1 polarisation capacities can migrate to lymph nodes after ID injection. (orig.)

  10. 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)

  11. 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

  12. 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

  13. 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)

  14. Binding of radiolabeled asbestos fibers to guinea pig (gp) alveolar macrophages (AM)

    International Nuclear Information System (INIS)

    Giannotti, M.A.; Tewson, T.J.; Francsechini, M.P.; Scheule, R.K.; Holian, A.

    1990-01-01

    The mechanism by which fibrogenic particulates cause pulmonary fibrosis in humans is not understood, but is likely to involve the AM. Using two fibrogenic particulates, namely, chrysotile (CHR) and crocidolite (CRO) asbestos and gpAM as components of an in vitro model system, the authors have shown that CHR stimulates the gpAM to release superoxide anion, but CRO does not. To examine whether this difference in stimulatory abilities is a result of differences in cell-asbestos binding they have developed an efficient procedure that radiolabels asbestos fibers while retaining their bioactivity. The fibers are labeled with 68 Ge. The 68 Ge decays into 68 Ga, which then can be detected by its characteristic position emission. Both CHR and CRO asbestos were radiolabled successfully. Mild reaction conditions and short reaction times were found under which >90% of the added 68 Ge and 68 Ga bound to the fibers. The radiolabel was retained even after washing the fibers extensively with physiologic buffers. A density gradient procedure was developed to quantitate the binding of asbestos to gpAM in suspension. The binding of both fibers increased with time over one hr. Thus, these results indicate that although both CHR and CRO interact with the gpAM, only CHR interacts productively to stimulate superoxide anion release

  15. 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

  16. Studies of the radiolabeling and biodistribution of substance P using lutetium-177 as a radiotracer

    International Nuclear Information System (INIS)

    Lima, Clarice Maria de

    2011-01-01

    Malignant gliomas are primary brain tumors, resistant to various treatments, as chemotherapy, radiotherapy, induction of apoptosis and surgery. An alternative for the treatment of malignant gliomas is the radionuclide therapy. This technique apply radiolabeled molecules that selectively bind to tumor cells producing cytotoxic effect by dose irradiation, and resulting in death of tumor cells. Most protocols for radionuclide therapy of malignant brain tumors involve the administration of peptides labeled with β - emitting radioisotopes. The Substance P (SP) is an 11- amino acid neuropeptide, characterized by the C-terminal sequence Phe-X-Gly-Leu-Met-NH 2 . The use of SP labeled with different radionuclides including 177 Lu, have been proposed for in vivo treatment of tumors. SP is the most important target of neurokinin 1 receptors, over expressed in malignant gliomas. The objective of this work was to study conditions of radiolabeling DOTA-SP with 177 Lu, the stability of labeled compound and in vivo and in vitro, to develop a protocol production and evaluate the potential of the radiopharmaceutical in the therapy of gliomas. The labeling conditions were optimized varying the temperature, reaction time, activity of lutetium-177 chloride and mass of DOTA-SP. The radiochemical purity of preparations were analyzed by chromatographic techniques. The stability of 17L u -DOTA- SP radiolabeled with low activity of 177 Lu was evaluated for different time at 2-8 degree C or incubated in human serum. The stability of the labeled with high activity of 177 Lu was also analyzed in the presence of gentisic acid (6 mg / mL) added after the labeling reaction. The labeled conditions in low and high activity were subjected to evaluation for the ability to cause oxidation of methionine residue, adding the D-L- methionine amino acid to the reaction medium (6 mg / mL) and subsequent chromatographic evaluation. In vitro study with 177 Lu-DOTA-SP, radiolabeled in the absence and presence

  17. 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.)

  18. 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)

  19. 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)

  20. Interpretation of animal data in the calculation of doses from new radiolabelled compounds

    International Nuclear Information System (INIS)

    Ellender, M.; Naylor, G.P.L.

    1992-01-01

    The Radionuclide Biokinetics Group of the Biomedical Effects Department at NRPB provides a dose calculation service for pharmaceutical companies and associated laboratories which plan to administer radiolabelled drugs to human volunteers as part of their research and development programmes for new compounds. Animal data provided by these companies are used to estimate the likely doses to humans from administration of the compound. The dose estimate then accompanies the pharmaceutical company's application for approval from the UK Administration of Radioactive Substances Advisory Committee (ARSAC). The method of calculation, the interpretation of the animal data and the range of results obtained are discussed. In addition, the effect of the use of the new ICRP tissue weighting factors in the calculations is considered. (Author)

  1. The interpretation of animal data in the calculation of doses from new radiolabeled compounds

    International Nuclear Information System (INIS)

    Naylor, G.P.L.; Ellender, M.; Harrison, J.D.

    1992-01-01

    At NRPB, dose calculations are performed for pharmaceutical companies wishing to obtain approval for human volunteer experiments. Animal data from one or more species are used to estimate the radiation doses to humans that would result from the administration of novel radiolabeled compounds. The calculations themselves are straightforward, but the animal data can be interpreted in different ways, leading to variations in the calculated dose. Doses to the gut compartments usually dominate the committed effective dose equivalent, but retention in other tissues may be important for some compounds. Long-term retention components in tissues can affect doses considerably, and the binding of many radiopharmaceuticals to melanin means that doses to the eye are particularly important. The effect of these considerations on calculating doses are considered, as well as the effect of changes in risk estimates and tissue weighting factors

  2. Radiolabelling of sperm cells with 99mTc-HMPAO. In vivo visualization of sperm cell migration in rabbits

    International Nuclear Information System (INIS)

    Bockisch, A.; Tennessee Univ., Knoxville, TN; Tennessee Univ., Knoxville, TN; Al-Hasani, S.; Ven, H.V.D.; Diedrich, K.; Krebs, D.; Posch, C.; Hotze, A.; Biersack, H.J.

    1989-01-01

    The present paper is the first descriptive radiolabeling of sperm cells in order to visualize their in vivo migration and imaging by scintigraphic technique, 99m Tc-HMPAO was used which combines favourable characteristics of both imaging modalities and radiation exposure. The radiolabeling yield was optimised for human sperm cells, and was increasing with the number of sperm cells, the amount of HMPAO, the 99m Tc-HMPAO concentration and the duration of the incubation. Incubation periods greater than 20 min, however, resulted only in a minor increase of labeling yield. A delay of more than 5 min between the labeling of the HMPAO with 99m Tc and initiation of the incubation of the sperm cells with the 99m Tc-HMPAO also decreased the maximum labeling yield. The radiolabeled cells were found to be stable and after 18 h > 93% of the activity was still bound to the sperm cells. After insemination of labeled sperm cells in ovulating rabbits the accumulation of the cells in the Fallopian tubes and their subsequent migration could be clearly visualized by scintigraphic techniques in vivo. (orig.) [de

  3. Renal uptake and retention of radiolabeled somatostatin, bombesin, neurotensin, minigastrin and CCK analogues: species and gender differences

    Energy Technology Data Exchange (ETDEWEB)

    Melis, Marleen [Department of Nuclear Medicine, Erasmus MC Rotterdam, 3015 CE Rotterdam (Netherlands)], E-mail: m.melis@erasmusmc.nl; Krenning, Eric P.; Bernard, Bert F.; Visser, Monique de; Rolleman, Edgar; Jong, Marion de [Department of Nuclear Medicine, Erasmus MC Rotterdam, 3015 CE Rotterdam (Netherlands)

    2007-08-15

    Introduction: During therapy with radiolabeled peptides, the kidney is most often the critical organ. Newly developed peptides are evaluated preclinically in different animal models before their application in humans. In this study, the renal retention of several radiolabeled peptides was compared in male and female rats and mice. Methods: After intravenous injection of radiolabeled peptides [somatostatin, cholecystokinin (CCK), minigastrin, bombesin and neurotensin analogues], renal uptake was determined in both male and female Lewis rats and C57Bl mice. In addition, ex vivo autoradiography of renal sections was performed to localize accumulated radioactivity. Results: An equal distribution pattern of renal radioactivity was found for all peptides: high accumulation in the cortex, lower accumulation in the outer medulla and no radioactivity in the inner medulla of the kidneys. In both male rats and mice, an increasing renal uptake was found: [{sup 111}In-DTPA]CCK8<[{sup 111}In-DTPA-Pro{sup 1},Tyr{sup 4}]bombesin{approx}[{sup 111}In-DTPA] neurotensin<[{sup 111}In-DTPA]octreotide<<[{sup 111}In-DTPA]MG0. Renal uptake of [{sup 111}In-DTPA]octreotide in rats showed no gender difference, and renal radioactivity was about constant over time. In mice, however, renal uptake in females was significantly higher than that in males and decreased rapidly over time in both genders. Moreover, renal radioactivity in female mice injected with [{sup 111}In-DTPA]octreotide showed a different localization pattern. Conclusions: Regarding the renal uptake of different radiolabeled peptides, both species showed the same ranking order. Similar to findings in patients, rats showed comparable and constant renal retention of radioactivity in both genders, in contrast to mice. Therefore, rats appear to be the more favorable species for the study of the renal retention of radioactivity.

  4. Renal uptake and retention of radiolabeled somatostatin, bombesin, neurotensin, minigastrin and CCK analogues: species and gender differences

    International Nuclear Information System (INIS)

    Melis, Marleen; Krenning, Eric P.; Bernard, Bert F.; Visser, Monique de; Rolleman, Edgar; Jong, Marion de

    2007-01-01

    Introduction: During therapy with radiolabeled peptides, the kidney is most often the critical organ. Newly developed peptides are evaluated preclinically in different animal models before their application in humans. In this study, the renal retention of several radiolabeled peptides was compared in male and female rats and mice. Methods: After intravenous injection of radiolabeled peptides [somatostatin, cholecystokinin (CCK), minigastrin, bombesin and neurotensin analogues], renal uptake was determined in both male and female Lewis rats and C57Bl mice. In addition, ex vivo autoradiography of renal sections was performed to localize accumulated radioactivity. Results: An equal distribution pattern of renal radioactivity was found for all peptides: high accumulation in the cortex, lower accumulation in the outer medulla and no radioactivity in the inner medulla of the kidneys. In both male rats and mice, an increasing renal uptake was found: [ 111 In-DTPA]CCK8 111 In-DTPA-Pro 1 ,Tyr 4 ]bombesin∼[ 111 In-DTPA] neurotensin 111 In-DTPA]octreotide 111 In-DTPA]MG0. Renal uptake of [ 111 In-DTPA]octreotide in rats showed no gender difference, and renal radioactivity was about constant over time. In mice, however, renal uptake in females was significantly higher than that in males and decreased rapidly over time in both genders. Moreover, renal radioactivity in female mice injected with [ 111 In-DTPA]octreotide showed a different localization pattern. Conclusions: Regarding the renal uptake of different radiolabeled peptides, both species showed the same ranking order. Similar to findings in patients, rats showed comparable and constant renal retention of radioactivity in both genders, in contrast to mice. Therefore, rats appear to be the more favorable species for the study of the renal retention of radioactivity

  5. In vitro evaluation of canine leukocytes radiolabeled in whole blood with 99mTc stannous colloid

    International Nuclear Information System (INIS)

    Abushhiwa, Mohamed H.; Salehi, Nouria S.; Whitton, Robert C.; Charles, Jennifer A.; Finnin, Peter J.; Lording, Peter M.; Caple, Ivan W.; Parry, Bruce W.

    2008-01-01

    Introduction: Technetium-99m stannous colloid ( 99m TcSnC)-labeled leukocytes are used to investigate a variety of inflammatory diseases in human medicine. The present study investigates the in vitro behavior of canine leukocytes labeled in whole blood with 99m TcSnC. Methods: Blood samples from 10 healthy dogs were labeled with 99m TcSnC using a standard procedure. The distribution of radioactivity among blood components (plasma, leukocyte layers and erythrocytes) was measured following separation of the radiolabeled samples across Histopaque density gradients. Phagocytic function of labeled and unlabeled leukocytes was estimated using zymosan particles. Labeling retention by leukocytes was determined at 1, 3, 4 and 7 h postlabeling. Results: The mean±standard error percentage of radioactivity associated with plasma, erythrocyte and leukocyte fractions was 2.0±0.21%, 55.5±0.60% and 42.5±0.54%, respectively (the last comprising 70.2±0.83% in polymorphonuclear leukocytes and 29.8±0.83% in mononuclear leukocytes). Labeled canine leukocytes had a phagocytic activity of 91.3±0.28% (control, 91.7±0.26%). The radiolabeled canine leukocytes retained 94.1±0.30% of radioactivity at 7 h postlabeling. Conclusions: Radiolabeling of canine leukocytes in whole blood with 99m TcSnC has minor adverse effect on their phagocytic function. The radiolabeled canine leukocytes retained a large percentage of radioactivity for at least 7 h postlabeling

  6. Radiolabeled blood cells: radiation dosimetry and significance

    International Nuclear Information System (INIS)

    Thakur, M.L.

    1986-01-01

    Over the past few years blood cells labeled with In-111 have become increasingly useful in clinical diagnosis and biomedical research. Indium-111 by the virtue of its physical characteristics and ability to bind to cell cytoplasmic components, provides an excellent cell tracer and thereby, allows investigators to monitor in vivo cell distribution by external imaging and help determine a course of regimen in treating life threatening diseases. Due to natural phenomena such as margination, blood pool, and reticuloendothelial cell activity, in the normal state, depending upon the cell type and the quality of cell preparations, 30%-50% of the administered radioactivity is immediately distributed in the liver, spleen and bone marrow. Over a period of time the radioactivity in these organs slightly increases and decays with a physical half-life of In-111. The resulting radiation dose to these organs ranges between 1-25 rads/mCi In-111 administered. The authors have developed a new In-111 labeling technique which preserves platelet ultrastructure and shown that human lymphocytes labeled with In-111 in mixed leukocytes preparations a) are only 0.003% of the total -body lymphocytes population and b) are killed. The consequence if any may be considered insignificant, particularly because 5.6% metaphases from normal men and 6.5% metaphases from normal women in the US have at least one chromosome aberration. Calculations have shown that the risk of fatal hematological malignancy, over a 30 year period, in recipients of 100 million lymphocytes labeled with 100 μCi In-111 is 1/million patients studied. This risk is less than 0.025% of the 1981 spontaneous cancer patient rate in the country. 32 references, 10 tables

  7. Radiolabeling with fluorine-18 of a protein, interleukin-1 receptor antagonist

    Energy Technology Data Exchange (ETDEWEB)

    Prenant, C., E-mail: cprenant@cyclopharma.f [Wolfson Molecular Imaging Centre, University of Manchester, Manchester (United Kingdom); Cawthorne, C. [Academic Department of Radiation Oncology, Christie NHS Foundation Trust, Manchester (United Kingdom); Fairclough, M. [Wolfson Molecular Imaging Centre, University of Manchester, Manchester (United Kingdom); Rothwell, N.; Boutin, H. [Faculty of Life Sciences, University of Manchester, Manchester (United Kingdom)

    2010-09-15

    IL-1RA is a naturally occurring antagonist of the pro-inflammatory cytokine interleukin-1 (IL-1) with high therapeutic promise, but its pharmacokinetic remains poorly documented. In this report, we describe the radiolabeling of recombinant human interleukin-1 receptor antagonist (rhIL-1RA) with fluorine-18 to allow pharmacokinetic studies by positron emission tomography (PET). rhIL-1RA was labeled randomly by reductive alkylation of free amino groups (the {epsilon}-amino group of lysine residues or amino-terminal residues) using [{sup 18}F]fluoroacetaldehyde under mild reaction conditions. Radiosyntheses used a remotely controlled experimental rig within 100 min and the radiochemical yield was in the range 7.1-24.2% (decay corrected, based on seventeen syntheses). We showed that the produced [{sup 18}F]fluoroethyl-rhIL-1ra retained binding specificity by conducting an assay on rat brain sections, allowing its pharmakokinetic study using PET.

  8. Use of isotopically radiolabelled GM3 ganglioside to study metabolic alterations in Salla disease

    International Nuclear Information System (INIS)

    Chigorno, Vanna; Valsecchi, Manuela; Nicolini, Marco; Sonnino, Sandro

    1997-01-01

    We report the preparation of radioactive GM3 ganglioside and its use in the study of sialic acid storage disorders. For the first time GM3 was isotopically radiolabelled in three positions of the molecule: at the sialic acid acetyl group, [ 3 H-Neu5Ac]GM3, at the Cl of the fatty acid moiety, [ 1 4C-Stearoyl]GM3, and at C3 of sphingosine, [ 3 H-Sph]GM3. The radioactive GM3 administered to cultured human fibroblasts from a patient suffering from Salla disease was taken up by the cells and metabolized. An analysis of the distribution of radioactivity within the ganglioside metabolic derivatives showed an accumulation of free sialic acid and ceramide in the pathological cells. (author). 25 refs., 2 figs., 1 tab

  9. 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

  10. 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

  11. 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)

  12. 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).

  13. 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)

  14. Comparative pharmacokinetics and biodistribution studies of {sup 99m}Tc-annexin V produced by different radiolabeling methods

    Energy Technology Data Exchange (ETDEWEB)

    Santos, Josefina da Silva; Pujatti, Priscilla Brunelli; Couto, Renata Martinussi; Mengatti, Jair; Araujo, Elaine Bortoleti de, E-mail: jssantos@usp.b, E-mail: priscillapujatti@yahoo.com.b, E-mail: renatamartinussicouto@yahoo.com.b, E-mail: jmengatti@ipen.b, E-mail: ebaraujo@ipen.b [Instituto de Pesquisas Energeticas e Nucleares (IPEN/CNEN-SP), Sao Paulo, SP (Brazil)

    2009-07-01

    The use of radiolabeled annexin A5 (ANXA5) to detect cell death in vivo has increased in the last years. Several {sup 99m}Tc-labeling techniques were reported using different cores, such as [{sup 99m}Tc=O]{sup +3}, [{sup 99m}Tc]HYNIC, [{sup 99m}Tcident toN]{sup +2} and [Tc(CO{sub 3})]{sup +1}. The goal of the present work was to evaluate the influence of {sup 99m}Tc cores in the biological behavior of radiolabeled ANXA5 in Swiss mice using [{sup 99m}Tc=O]{sup +3}, [{sup 99m}Tc]HYNIC cores. Ethylenedicysteine (EC) was applied to obtain [Tc=O]{sup +3} core, N,N,N',N'-tetramethyl(succinimide) uranium tetrafluoroborate (TSTU) was employed to transfer the carboxyl group to their corresponding hydroxysuccinimide ester and HYNIC-ANXA5 was provided by National Cancer Institute-Frederick. ITLC-SG and HPLC analysis were applied to determine non-desirable products and the stability of preparations was evaluated after incubation at room temperature, 4 deg C and in human serum at 37 deg C. In vivo biodistribution and kinetics studies were performed after the intravenous injection of {sup 99m}Tc-HYNIC-ANXA5 and {sup 99m}Tc-EC-ANXA5 and pharmacokinetic parameters were calculated using Biexp software. ANXA5 was radiolabeled at room temperature with high yield (> 95%). The results of biodistribution in mice showed, as expected, higher renal uptake of {sup 99m}Tc-HYNICANXA5 and higher liver uptake of {sup 99m}Tc-EC-ANXA5. The percent injected activity per gram (% IA/g) in liver at 0.5 hours were 6.52 and 1.09 and in kidneys were 1.59 and 32.2 for {sup 99m}Tc-EC-ANXA5 and {sup 99m}Tc-HYNICANXA5, respectively. The results of radioactivity in blood showed that both HYNIC- and EC- radiolabeled ANXA5 presented fast blood clearance. In this study two {sup 99m}Tc-ANXA5 obtained from three different available radiolabeling methods presently were investigated. Each labeling method possesses unique advantages and disadvantages. (author)

  15. Comparative pharmacokinetics and biodistribution studies of 99mTc-annexin V produced by different radiolabeling methods

    International Nuclear Information System (INIS)

    Santos, Josefina da Silva; Pujatti, Priscilla Brunelli; Couto, Renata Martinussi; Mengatti, Jair; Araujo, Elaine Bortoleti de

    2009-01-01

    The use of radiolabeled annexin A5 (ANXA5) to detect cell death in vivo has increased in the last years. Several 99m Tc-labeling techniques were reported using different cores, such as [ 99m Tc=O] +3 , [ 99m Tc]HYNIC, [ 99m Tc≡N] +2 and [Tc(CO 3 )] +1 . The goal of the present work was to evaluate the influence of 99m Tc cores in the biological behavior of radiolabeled ANXA5 in Swiss mice using [ 99m Tc=O] +3 , [ 99m Tc]HYNIC cores. Ethylenedicysteine (EC) was applied to obtain [Tc=O] +3 core, N,N,N',N'-tetramethyl(succinimide) uranium tetrafluoroborate (TSTU) was employed to transfer the carboxyl group to their corresponding hydroxysuccinimide ester and HYNIC-ANXA5 was provided by National Cancer Institute-Frederick. ITLC-SG and HPLC analysis were applied to determine non-desirable products and the stability of preparations was evaluated after incubation at room temperature, 4 deg C and in human serum at 37 deg C. In vivo biodistribution and kinetics studies were performed after the intravenous injection of 99m Tc-HYNIC-ANXA5 and 99m Tc-EC-ANXA5 and pharmacokinetic parameters were calculated using Biexp software. ANXA5 was radiolabeled at room temperature with high yield (> 95%). The results of biodistribution in mice showed, as expected, higher renal uptake of 99m Tc-HYNICANXA5 and higher liver uptake of 99m Tc-EC-ANXA5. The percent injected activity per gram (% IA/g) in liver at 0.5 hours were 6.52 and 1.09 and in kidneys were 1.59 and 32.2 for 99m Tc-EC-ANXA5 and 99m Tc-HYNICANXA5, respectively. The results of radioactivity in blood showed that both HYNIC- and EC- radiolabeled ANXA5 presented fast blood clearance. In this study two 99m Tc-ANXA5 obtained from three different available radiolabeling methods presently were investigated. Each labeling method possesses unique advantages and disadvantages. (author)

  16. In vitro evaluation, biodistribution and scintigraphic imaging in mice of radiolabeled anthrax toxins

    International Nuclear Information System (INIS)

    Dadachova, Ekaterina; Rivera, Johanna; Revskaya, Ekaterina; Nakouzi, Antonio; Cahill, Sean M.; Blumenstein, Michael; Xiao, Hui; Rykunov, Dmitry; Casadevall, Arturo

    2008-01-01

    Introduction: There is a lot of interest towards creating therapies and vaccines for Bacillus anthracis, a bacterium which causes anthrax in humans and which spores can be made into potent biological weapons. Systemic injection of lethal factor (LF), edema factor (EF) and protective antigen (PA) in mice produces toxicity, and this protocol is commonly used to investigate the efficacy of specific antibodies in passive protection and vaccine studies. Availability of toxins labeled with imageable radioisotopes would allow to demonstrate their tissue distribution after intravenous injection at toxin concentration that are below pharmacologically significant to avoid masking by toxic effects. Methods: LF, EF and PA were radiolabeled with 188 Re and 99m Tc, and their performance in vitro was evaluated by macrophages and Chinese hamster ovary cells toxicity assays and by binding to macrophages. Scintigraphic imaging and biodistribution of intravenously (IV) injected 99m Tc-and 123 I-labeled toxins was performed in BALB/c mice. Results: Radiolabeled toxins preserved their biological activity. Scatchard-type analysis of the binding of radiolabeled PA to the J774.16 macrophage-like cells revealed 6.6x10 4 binding sites per cell with a dissociation constant of 6.7 nM. Comparative scintigraphic imaging of mice injected intravenously with either 99m Tc-or 123 I-labeled PA, EF and LF toxins demonstrated similar biodistribution patterns with early localization of radioactivity in the liver, spleen, intestines and excretion through kidneys. The finding of renal excretion shortly after IV injection strongly suggests that toxins are rapidly degraded which could contribute to the variability of mouse toxigenic assays. Biodistribution studies confirmed that all three toxins concentrated in the liver and the presence of high levels of radioactivity again implied rapid degradation in vivo. Conclusions: The availability of 188 Re and 99m Tc-labeled PA, LF and EF toxins allowed us to

  17. 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

  18. The alginate layer for improving doxorubicin release and radiolabeling stability of chitosan hydrogels

    Energy Technology Data Exchange (ETDEWEB)

    Kwon, Jeong Il; Lee, Chang Moon; Jeong, Hwan Seok; Hwang, Hyo Sook; Lim, Seok Tae; Sohn, Myung Hee; Jeong, Hwan Jeong [Dept. of Nuclear Medicine and Therapeutic Medicine Research Center, Cyclotron Research Center, Institute for Medical Science, Biomedical Research Institute, Chonbuk National University Medical School, Jeonju (Korea, Republic of); Lee, Chang Moon [Dept. of Biomedical Engineering, Chonnam National University, Yeosu (Korea, Republic of)

    2015-12-15

    Chitosan hydrogels (CSH) formed through ionic interaction with an anionic molecule are suitable as a drug carrier and a tissue engineering scaffold. However, the initial burst release of drugs from the CSH due to rapid swelling after immersing in a biofluid limits their wide application as a drug delivery carrier. In this study, alginate layering on the surface of the doxorubicin (Dox)-loaded and I-131-labeled CSH (DI-CSH) was performed. The effect of the alginate layering on drug release behavior and radiolabeling stability was investigated. Chitosan was chemically modified using a chelator for I-131 labeling. After labeling of I-131 and mixing of Dox, the chitosan solution was dropped into tripolyphosphate (TPP) solution using an electrospinning system to prepare spherical microhydrogels. The DI-CSH were immersed into alginate solution for 30 min to form the crosslinking layer on their surface. The formation of alginate layer on the DI-CSH was confirmed by Fourier transform infrared spectroscopy (FT-IR) and zeta potential analysis. In order to investigate the effect of alginate layer, studies of in vitro Dox release from the hydrogels were performed in phosphate buffered in saline (PBS, pH 7.4) at 37 °C for 12 days. The radiolabeling stability of the hydrogels was evaluated using ITLC under different experimental condition (human serum, normal saline, and PBS) at 37 °C for 12 days. Formatting the alginate-crosslinked layer on the CSH surface did not change the spherical morphology and the mean diameter (150 ± 10 μm). FT-IR spectra and zeta potential values indicate that alginate layer was formed successfully on the surface of the DI-CSH. In in vitro Dox release studies, the total percentage of the released Dox from the DI-CSH for 12 days were 60.9 ± 0.8, 67.3 ± 1.4, and 71.8 ± 2.5 % for 0.25, 0.50, and 1.00 mg Dox used to load into the hydrogels, respectively. On the other hand, after formatting alginate layer, the percentage of the

  19. 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

  20. In vitro and in vivo motility studies of radiolabelled sperm cells

    International Nuclear Information System (INIS)

    Balogh, L.; Szasz, F.; Janoki, Gy.A.; Toth, L.; Zoldag, L.; Huszenicza, Gy.

    1994-01-01

    A new method for radiolabelling of sperm cells with 99m Tc HM-PAO (hexamethyl-propylene-amine-oxide) - LEUCO-SCINT kit, is investigated. The labelling technique for fresh rabbit, bull, sheep and horse as well as frozen-thawed bull sperm was optimized. The optimum conditions for sperm cell labelling (incubation volume, incubation time, initial activity of 99m Tc HM-PAO, cell number) yielded a high labelling efficiency (70-80%) and survival rate (50-60%). The labelled sperm cells were used to study their motility in vitro. The migrating at 37 o C cells incubated capillary tubes containing bovine cervical mucus. The tubes were cut and the activity of the parts measured and valued. We compared the results of living and killed sperm cells and the label alone by the change of species and running time. Ten minutes after the labelling procedures the total activity of microtubes was 2-3 times higher and the activity distribution was different from the results obtained 3 hours after the labelling. The sperm migration in vivo in the living female animals using a non invasive technique was also visualized. The sperm flow was clearly demonstrated in 3 different animal model (rabbit, ewe, hen) under gamma camera. The comparison of the in vivo migration of rabbit and bull sperm cells showed that the homologous sperm migrated faster and farther. On study of bull sperm migration in the ewe genital tract the cornu uteri was clearly visualized. In the hen model the whole genital tract was demonstrated with considerable free activity in the cavum abdominal 24 hours after the artificial insemination. The new method is developed and manufactured by NRIRR, Budapest, originally designed for radiolabelling leucocytes. The 99m Tc HM-PAO Labelled sperm cells with their retained migration properties are suitable for in vitro motility assays and in vitro migration studies in both human and veterinary medicine. (author)

  1. Radiolabeled adenoviral sub-unit proteins for molecular imaging and therapeutic applications in oncology

    International Nuclear Information System (INIS)

    Srivastava, Suresh C.

    2005-01-01

    Full text: Our group has initiated investigations on the use of radiolabeled adenoviral (Ad) sub-unit proteins for delivering suitable radionuclides into tumor cells for molecular imaging as well as for combined gene/radionuclide therapy of cancer. A number of issues involved in developing combined gene/radionuclide delivery into tumors mediated by Ad vectors have been identified and are being addressed. Whereas current clinical trials of gene therapy using Ad vectors involve non-systemic delivery of therapeutic genes, the delivery of radionuclides preferably would involve systemic (i.v.) administration. The distribution and delivery of Ad sub-unit proteins following i.v. administration is not understood and must be studied and optimized. In addition, retention of the selective binding and internalization into tumor cells of the radiolabeled viral vectors remains an unmet challenge. We used the intact adenovirus (Ad, ∼80 nm diameter), native adenoviral fiber protein (AdFP, 180 kD trimer, purified from infected human cultured cells) and the adenoviral fiber 'knob' protein (recombinant AdFKP, 60 kD, synthesized in E. Coli), all of which interact with the in-vivo cellular receptor, coxsackie and adenovirus receptor (CAR) through the knob domain of the adenovirus fiber protein. Our initial studies were aimed at optimizing the labeling conditions using I-131 and In-111 to maintain CAR binding activity of the radiolabeled preparations. The CAR-binding was retained as determined using reaction with biotinylated CAR followed by chemiluminescence detection. The biodistribution results in mice and rats following i.v. administration (autoradiography, tissue counting) showed that all three vectors localized preferentially in CAR-expressing organs (liver, lung, heart, kidney), as expected. The CAR-binding of Ad-2 wild serotype was better (∼8 x stronger) than Ad-12, in particular following radiolabeling. Based on the above results, we further focused on the recombinant knob

  2. 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...

  3. 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

  4. 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

  5. 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)

  6. 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

  7. 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

  8. 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)

  9. 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...

  10. 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)

  11. 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)

  12. Synthesis, radiolabeling and quality control of {sup 111}In-DOTA-bevacizumab for radioimmunoscintigraphy of VEGF receptors

    Energy Technology Data Exchange (ETDEWEB)

    Khorami-Moghadam, A.; Jalilian, A.R.; Yavari, K.; Alirezapour, B.; Mazidi, M.; Mirzaii, M. [Nuclear Science and Technology Research Institute (NSTRI), Tehran (Iran, Islamic Republic of)

    2013-11-01

    In this study, bevacizumab was successively labeled with {sup 111}In-InCl{sub 3} after conjugation with DOTA-NHS-ester followed by molecular filtration and determination of the average number ofDOTAconjugated per mAb (6:1) by spectrophotometric method. Radiochemical purity (> 97%, measured by ITLC and HPLC), integrity of protein after radiolabeling (gel electrophoresis) and stability of {sup 111}In-DOTA-Bevacizumab (in final formulation, human serum, liver/kidney homogenates) were determined in 24-72 h as well as biodistribution studies in wild-type rats and human colon cancer (SW-480) bearing mice. The accumulation of the radiolabeled antibody was consistent with the former reported Bevacizumab conjugates. Significant tumor uptake (8%) was observed at 72 h p.i. Tumor/muscle uptake ratios were 2.6 (24 h), 9.74 (48 h) and 25 (72 h). {sup 111}In-DOTA-Bevacizumab was prepared as a SPECT molecular imaging agent for diagnosis and follow-up of vascular endothelial growth factor A (VEGF-A) expression in oncology. (orig.)

  13. Radiolabeled enzyme inhibitors and binding agents targeting PSMA: Effective theranostic tools for imaging and therapy of prostate cancer

    International Nuclear Information System (INIS)

    Pillai, Maroor Raghavan Ambikalmajan; Nanabala, Raviteja; Joy, Ajith; Sasikumar, Arun; Knapp, Furn F.

    2016-01-01

    Because of the broad incidence, morbidity and mortality associated with prostate-derived cancer, the development of more effective new technologies continues to be an important goal for the accurate detection and treatment of localized prostate cancer, lymphatic involvement and metastases. Prostate-specific membrane antigen (PSMA; Glycoprotein II) is expressed in high levels on prostate-derived cells and is an important target for visualization and treatment of prostate cancer. Radiolabeled peptide targeting technologies have rapidly evolved over the last decade and have focused on the successful development of radiolabeled small molecules that act as inhibitors to the binding of the N-acetyl-L-aspartyl-L-glutamate (NAAG) substrate to the PSMA molecule. A number of radiolabeled PSMA inhibitors have been described in the literature and labeled with SPECT, PET and therapeutic radionuclides. Clinical studies with these agents have demonstrated the improved potential of PSMA-targeted PET imaging agents to detect metastatic prostate cancer in comparison with conventional imaging technologies. Although many of these agents have been evaluated in humans, by far the most extensive clinical literature has described use of the 68 Ga and 177 Lu agents. This review describes the design and development of these agents, with a focus on the broad clinical introduction of PSMA targeting motifs labeled with 68 Ga for PET-CT imaging and 177 Lu for therapy. In particular, because of availability from the long-lived 68 Ge (T 1/2 = 270 days)/ 68 Ga (T 1/2 = 68 min) generator system and increasing availability of PET-CT, the 68 Ga-labeled PSMA targeted agent is receiving widespread interest and is one of the fastest growing radiopharmaceuticals for PET-CT imaging.

  14. Evaluation of radiolabeling of annexin A5 with technetium-99m: influence of the labeling methods on physico-chemical and biological properties of the compounds

    International Nuclear Information System (INIS)

    Santos, Josefina da Silva

    2009-01-01

    Annexin A5 (ANXA5) is an intracellular human protein of 36 kDa with high affinity for membrane-bound phosphatidylserine that is selectively exposed on the surface of cells undergoing apoptosis. Apoptosis is important in normal physiology and innumerous pathologic states. Clinical applications for ANXA5 imaging are being developed in oncology, organ transplantation and cardiovascular diseases. Many strategies to radiolabel the protein have been described, including direct labeling, derivatization through a bifunctional chelating agent (BFC), production of mutated protein or peptide analogs. Several 99 mTc-labeling techniques have been reported using different cores, including [Tc=O] +3 , [Tc]HYNIC, [Tc≡N]+2 and [Tc(CO 3 )] +1 . In this study, we evaluated the influence of 99 mTc cores on biological behavior and physico-chemical properties of radiolabeled annexin. Radiolabeling procedure using [Tc≡N] +2 core was a two-step procedure including the reaction of 99 mTcO4 - with SDH in the presence of SnCl 2 and PDTA to obtain the intermediate 99 mTcN-SDH, and successive addition of ANXA5. The results obtained were not satisfactory, despite the high efficiency in the production of the intermediate. The [Tc=O] +3 core was produced using the ethylene dicysteine (EC) as BFC. TSTU was employed in the derivatization to produce the corresponding hydroxysuccinimide ester. Different ANXA5:EC ratios were studied and all labeling conditions resulted in high radiochemical yield but with differences in lipophilicity, stability, biological distribution and affinity for apoptotic cells. The HYNIC-ANXA5 also produced the labeled protein with high radiochemical yield. The stability of the radiolabeled ANXA5 was evaluated after storing at room temperature, at 2 - 8 degree C and in human serum at 37 degree C. The analysis of these results showed that the 99 mTc-EC-ANXA5 (ratio 10-2) was the most stable compound in all the studied conditions. Partition coefficient assay resulted in

  15. 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)

  16. /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

  17. 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

  18. 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.

  19. An improved radiolabelled RNA aptamer molecule for HER2 imaging in cancers.

    Science.gov (United States)

    Varmira, Kambiz; Hosseinimehr, Seyed Jalal; Noaparast, Zohreh; Abedi, Seyed Mohammad

    2014-02-01

    Human epidermal growth factor receptor 2 (HER2) expression has been shown to be increased in several types of human tumours. In this study, for the imaging of HER2-related tumours, a modified RNA aptamer with HER2-specific targeting was labelled with (99m)Tc, by using hydrazino nicotinamide (HYNIC) as the chelator in the presence of tricine or ethylenediamine-N,N'-diacetic acid (EDDA) as the co-ligand. Stability testing of the radiolabelled aptamers in the serum was performed through SDS-PAGE. The aptamer-radionuclide conjugate was evaluated for its cellular HER2-specific binding in ovarian cancer cells (SKOV-3), and its biodistribution properties were assessed in normal and SKOV-3 tumour-bearing mice. In the presence of either tricine or EDDA, the HYNIC-RNA aptamers were labelled with (99m)Tc at a high yield and radiochemical purity. Cellular experiments confirmed the specific binding of the RNA aptamer to the HER2 receptor. In the animal biodistribution study, uptake of the EDDA-co-liganded (99m)Tc-HYNIC-RNA aptamer by the liver and spleen was remarkably lower than that of the aptamer with tricine. Tumours also showed a higher accumulation of radioactivity with the EDDA-co-liganded aptamer complex. This study demonstrated EDDA to be better than tricine for use as a co-ligand with the RNA aptamer, which can be a potential tool for the molecular imaging of HER2-overexpressing cancers.

  20. Cardiac output by Doppler echocardiography in the premature baboon: Comparison with radiolabeled microspheres

    International Nuclear Information System (INIS)

    Kinsella, J.P.; Morrow, W.R.; Gerstmann, D.R.; Taylor, A.F.; deLemos, R.A.

    1991-01-01

    Pulsed-Doppler echocardiography (PDE) is a useful noninvasive method for determining left ventricular output (LVO). However, despite increasingly widespread use in neonatal intensive care units, validation studies in prematures with cardiopulmonary disease are lacking. The purpose of this study was to compare radiolabeled microsphere (RLM) and PDE measurements of LVO, using the critically ill premature baboon as a model of the human neonate. Twenty-two paired RLM and PDE measurements of LVO were obtained in 14 animals between 3 and 24 h of age. Average PDE LVO was 152 ml/min/kg (range, 40-258 ml/min/kg) compared to 158 ml/min/kg (range, 67-278 ml/min/kg) measured by RLM. Linear regression analysis of the paired measurements showed good correlation with a slope near unity (gamma = 0.94x + 4.20, r = 0.91, SEE = 25.7 ml). The authors conclude that PDE determinations of LVO compare well with those measured by RLM in the premature baboon. PDE appears to provide a valid estimate of LVO and should be useful in human prematures with cardiopulmonary distress

  1. 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

  2. SSTR-Mediated Imaging in Breast Cancer: Is There a Role for Radiolabeled Somatostatin Receptor Antagonists?

    Science.gov (United States)

    Dalm, Simone U; Haeck, Joost; Doeswijk, Gabriela N; de Blois, Erik; de Jong, Marion; van Deurzen, Carolien H M

    2017-10-01

    Recent studies have shown enhanced tumor targeting by novel somatostatin receptor (SSTR) antagonists compared with clinically widely used agonists. However, these results have been obtained mostly in neuroendocrine tumors, and only limited data are available for cancer types with lower SSTR expression, including breast cancer (BC). To date, two studies have reported higher binding of the antagonist than the agonist in BC, but in both studies only a limited number of cases were evaluated. In this preclinical study, we further investigated whether the application of an SSTR antagonist can improve SSTR-mediated BC imaging in a large panel of BC specimens. We also generated an in vivo BC mouse model and performed SPECT/MRI and biodistribution studies. Methods: Binding of 111 In-DOTA-Tyr 3 -octreotate (SSTR agonist) and 111 In-DOTA-JR11 (SSTR antagonist) to 40 human BC specimens was compared using in vitro autoradiography. SSTR2 immunostaining was performed to confirm SSTR2 expression of the tumor cells. Furthermore, binding of the radiolabeled SSTR agonist and antagonist was analyzed in tissue material from 6 patient-derived xenografts. One patient-derived xenograft, the estrogen receptor-positive model T126, was chosen to generate in vivo mouse models containing orthotopic breast tumors for in vivo SPECT/MRI and biodistribution studies after injection with 177 Lu-DOTA-Tyr 3 -octreotate or 177 Lu-DOTA-JR11. Results: 111 In-DOTA-JR11 binding to human BC tissue was significantly higher than 111 In-DOTA-Tyr 3 -octreotate binding ( P < 0.001). The median ratio of antagonist binding versus agonist binding was 3.39 (interquartile range, 2-5). SSTR2 immunostaining confirmed SSTR2 expression on the tumor cells. SPECT/MRI of the mouse model found better tumor visualization with the antagonist. This result was in line with the significantly higher tumor uptake of the radiolabeled antagonist than of the agonist as measured in biodistribution studies 285 min after radiotracer

  3. 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)

  4. Characterization of the radiolabeled metabolite of tau PET tracer 18F-THK5351

    International Nuclear Information System (INIS)

    Harada, Ryuichi; Furumoto, Shozo; Tago, Tetsuro; Iwata, Ren; Tashiro, Manabu; Katsutoshi, Furukawa; Ishiki, Aiko; Tomita, Naoki; Arai, Hiroyuki; Yanai, Kazuhiko; Kudo, Yukitsuka; Okamura, Nobuyuki

    2016-01-01

    18 F-THK5351 is a novel radiotracer developed for in vivo imaging of tau pathology in the brain. For the quantitative assessment of tau deposits in the brain, it is important that the radioactive metabolite does not enter the brain and that it does not bind to tau fibrils. The purpose of the study was to identify a radiolabeled metabolite of 18 F-THK5351 in blood samples from human subjects and to characterize its pharmacological properties. Venous blood samples were collected from three human subjects after injection of 18 F-THK5351 and the plasma metabolite was measured by high performance thin layer chromatography. In addition, mass spectrometry analysis and enzymatic assays were used to identify this metabolite. Mice were used to investigate the blood-brain barrier permeability of the radioactive metabolite. Furthermore, the binding ability of the metabolite to tau aggregates was evaluated using autoradiography and binding assays using human brain samples. About 13 % of the unmetabolized radiotracer was detectable in human plasma at 60 min following the injection of 18 F-THK5351. The isolated radiometabolite of 18 F-THK5351 was the sulphoconjugate of THK5351. This metabolite could be produced in vitro by incubating THK5351 with liver but not brain homogenates. The metabolite did not penetrate the blood-brain barrier in mice, and exhibited little binding to tau protein aggregates in post-mortem human brain samples. These results suggest that the sole metabolite detectable in plasma seems to be generated outside the brain and does not cross into the brain, which does not affect quantitative analysis of PET images. (orig.)

  5. Characterization of the radiolabeled metabolite of tau PET tracer {sup 18}F-THK5351

    Energy Technology Data Exchange (ETDEWEB)

    Harada, Ryuichi [Tohoku University, Division of Neuro-imaging, Institute of Development, Aging and Cancer, Sendai (Japan); Furumoto, Shozo; Tago, Tetsuro; Iwata, Ren; Tashiro, Manabu [Tohoku University, Cyclotron and Radioisotope Center, Sendai (Japan); Katsutoshi, Furukawa; Ishiki, Aiko; Tomita, Naoki; Arai, Hiroyuki [Tohoku University, Department of Geriatrics and Gerontology, Institute of Development, Aging and Cancer, Sendai (Japan); Yanai, Kazuhiko [Tohoku University, Cyclotron and Radioisotope Center, Sendai (Japan); Tohoku University School of Medicine, Department of Pharmacology, Sendai (Japan); Kudo, Yukitsuka [Tohoku University, Division of Neuro-imaging, Institute of Development, Aging and Cancer, Sendai (Japan); Tohoku University, Cyclotron and Radioisotope Center, Sendai (Japan); Okamura, Nobuyuki [Tohoku University, Division of Neuro-imaging, Institute of Development, Aging and Cancer, Sendai (Japan); Tohoku University, Cyclotron and Radioisotope Center, Sendai (Japan); Tohoku Medical and Pharmaceutical University, Division of Pharmacology, Faculty of Medicine, Sendai (Japan)

    2016-11-15

    {sup 18}F-THK5351 is a novel radiotracer developed for in vivo imaging of tau pathology in the brain. For the quantitative assessment of tau deposits in the brain, it is important that the radioactive metabolite does not enter the brain and that it does not bind to tau fibrils. The purpose of the study was to identify a radiolabeled metabolite of {sup 18}F-THK5351 in blood samples from human subjects and to characterize its pharmacological properties. Venous blood samples were collected from three human subjects after injection of {sup 18}F-THK5351 and the plasma metabolite was measured by high performance thin layer chromatography. In addition, mass spectrometry analysis and enzymatic assays were used to identify this metabolite. Mice were used to investigate the blood-brain barrier permeability of the radioactive metabolite. Furthermore, the binding ability of the metabolite to tau aggregates was evaluated using autoradiography and binding assays using human brain samples. About 13 % of the unmetabolized radiotracer was detectable in human plasma at 60 min following the injection of {sup 18}F-THK5351. The isolated radiometabolite of {sup 18}F-THK5351 was the sulphoconjugate of THK5351. This metabolite could be produced in vitro by incubating THK5351 with liver but not brain homogenates. The metabolite did not penetrate the blood-brain barrier in mice, and exhibited little binding to tau protein aggregates in post-mortem human brain samples. These results suggest that the sole metabolite detectable in plasma seems to be generated outside the brain and does not cross into the brain, which does not affect quantitative analysis of PET images. (orig.)

  6. 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)

  7. 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

  8. 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

  9. 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

  10. 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

  11. Radiolabeling of substance P with Lutetium-177 and biodistribution study in AR42J pancreatic tumor xenografted Nude mice

    International Nuclear Information System (INIS)

    Araujo, Bortoleti de; Pujatti, Priscilla Brunelli; Barrio, Ofelia; Caldeira, Jose S.; Mengatti, Jair; Suzuki, Miriam F.

    2008-01-01

    Pancreatic tumor (PT) is a neuroendocrine neoplasm that usually origin metastases in the respiratory and gastrointestinal tract. In recent years, new developments in targeted therapies have emerged and the presence of peptide receptors at the cell membrane of PT constitutes the basis of the clinical use of specific radiolabeled ligands. Substance P, an 11-amino acid peptide which has an important role in modulating pain transmission trough neurokinin 1 and 2 receptors (NKr), may play a role in the pathogenesis of PT, because approximately 10% of these tumors over express NKr. The aim of the present work was to produce a pure and stable SP analog (DOTA-SP) radiolabeled with Lutetium-177 ( 177 Lu), and to evaluate its in vivo target to AR42J pancreatic tumor cells in Nude mice in other to verify if SP can be used in this pancreatic tumor detection and treatment. 177 Lu (half-life 6.7 days) has both β and γ-emissions suitable for radiotherapy and imaging respectively. Substance P was successfully labeled with high yield (>99%) at optimized conditions and kept stable for more than 72 hours at 4 deg C and 24 hours in human plasma. Biodistribution studies showed that SP excretion was mainly performed by renal pathway. In addition, 177 Lu-DOTA-SP showed higher uptake by tumor than normal pancreas, indicating the presence of NK receptors in AR42J pancreatic tumor. (author)

  12. 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

  13. 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

  14. 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

  15. 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)

  16. 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.

  17. 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

  18. 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.

  19. 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)

  20. 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)

  1. 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

  2. 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

  3. 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)

  4. 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

  5. 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

  6. A standardised study to compare prostate cancer targeting efficacy of five radiolabelled bombesin analogues

    Energy Technology Data Exchange (ETDEWEB)

    Schroeder, Rogier P.J. [Erasmus MC, Department of Nuclear Medicine, Rotterdam (Netherlands); Erasmus MC, Department of Experimental Urology, Rotterdam (Netherlands); Mueller, Cristina; Melis, Marleen L.; Breeman, Wout A.P.; Blois, Erik de; Krenning, Eric P.; Jong, Marion de [Erasmus MC, Department of Nuclear Medicine, Rotterdam (Netherlands); Reneman, Suzanne; Bangma, Chris H.; Weerden, Wytske M. van [Erasmus MC, Department of Experimental Urology, Rotterdam (Netherlands)

    2010-07-15

    Prostate-specific antigen (PSA)-based screening for prostate cancer (PC) has dramatically increased early diagnosis. Current imaging techniques are not optimal to stage early PC adequately. A promising alternative to PC imaging is peptide-based scintigraphy using radiolabelled bombesin (BN) analogues that bind to gastrin-releasing peptide receptors (GRPR) being overexpressed in PC. When labelled to appropriate radionuclides BN targeting of GRPRs may also provide applications for peptide radionuclide receptor therapy (PRRT). Assessment studies under identical experimental conditions allowing a reliable comparison of the potential of such analogues are lacking. This study was performed to evaluate and directly compare five promising radiolabelled BN analogues for their targeting efficacy for PC under standardised conditions. The BN agonists [{sup 111}In]DOTA-PESIN, [{sup 111}In]AMBA, [{sup 111}In]MP2346 and [{sup 111}In]MP2653 and one antagonist [{sup 99m}Tc]Demobesin-1 were evaluated in GRPR-overexpressing human PC-3 tumour-bearing mice to determine peptide stability in vivo, biodistribution and GRPR targeting potential by animal SPECT/CT imaging and ex vivo autoradiography. HPLC analysis of blood showed intact Demobesin-1 at 5 and 15 min after injection (64.1{+-}1.6% and 41.0{+-}01%, respectively) being much less for the other compounds. AMBA, the second most stable analogue, showed 36.1{+-}2.7% and 9.8{+-}1.1% intact peptide after 5 and 15 min. PC-3 tumour uptake at 1 h was comparable for Demobesin-1, AMBA, PESIN and MP2346 (3.0{+-}0.4, 2.7{+-}0.5, 2.3{+-}0.5 and 2.1{+-}0.9%ID/g, respectively), but very low for MP2653 (0.9 {+-} 0.2%ID/g). In addition, MP2346 showed undesirably high uptake in the kidneys (7.9{+-}1.9%ID/g) being significantly less for the other analogues. AMBA, MP2346 and PESIN revealed favourable increases in tumour to blood ratios over time while changes in tumour to kidney and pancreas ratios for Demobesin-1 from 1 to 24 h after injection were

  7. Cardiovascular side-effects and insulin secretion after intravenous administration of radiolabeled Exendin-4 in pigs

    International Nuclear Information System (INIS)

    Rydén, Anneli; Nyman, Görel; Nalin, Lovisa; Andreasson, Susanne; Korsgren, Olle; Eriksson, Olof; Jensen-Waern, Marianne

    2016-01-01

    Introduction: Radiolabeled Exendin-4, a synthetic glucagon-like peptide-1 (GLP-1) analog, is used as a tracer for diagnostic purposes of β-cells and in experimental animal research. Exendin-4 can be radiolabeled with 68 Ga, 111 In or 99m Tc and used for positron emission tomography (PET) and single-photon emission computed tomography (SPECT) imaging to diagnose insulinomas, visualization of pancreatic β-cell mass and transplanted Islets of Langerhans. In humans, Exendin-4 is widely used as a therapeutic agent for treatment of type 2 diabetes (T2D). The compound, which is administered subcutaneously (SC) may cause nausea, vomiting and a minor increase in the heart rate (HR). However, possible side-effects on cardiovascular functions after intravenous (IV) administration have not been reported. This study describes the Exendin-4 dose at which cardiovascular side-effects occur in pigs and cynomolgus monkeys. The IV effect of the tracer on insulin secretion is also investigated in pigs. Methods: Seven clinically healthy littermate pigs (40 days old) were used; three of them were made diabetic by streptozotocin (STZ). All pigs underwent PET imaging under general anesthesia to examine the glucagon-like peptide-1 receptor (GLP-1R) in β-cells with radiolabeled Exendin-4. A baseline tracer dose IV [ 68 Ga]Exendin-4 (0.025 ± 0.010 μg/kg) followed by a competition dose IV [ 68 Ga]Exendin-4 (3.98 ± 1.33 μg/kg) 60 min later were administered. Blood samples were taken and analyzed for insulin secretion by using ELISA. Cardiovascular and respiratory variables were monitored throughout the experiment. Results: Immediately after administration of the high dose [ 68 Ga]Exendin-4 the HR rose from 122 ± 14 to 227 ± 40 bpm (p < 0.01) and from 100 ± 5 to 181 ± 13 bpm (p < 0.01) in healthy non-diabetic and diabetes-induced pigs, respectively. The tachycardia was observed for > 2 h and one healthy non-diabetic pig suffered cardiac arrest 3 h after the IV [ 68 Ga]Exendin-4

  8. Genetic induction of the gastrin releasing peptide receptor on tumor cells for radiolabeled peptide binding

    International Nuclear Information System (INIS)

    Raben, David; Stackhouse, Murray; Buchsbaum, Donald J.; Mikheeva, Galeena; Khazaeli, M.B.; McLean, Stephanie; Kirkman, Richard; Krasnykh, Victor; Curiel, David T.

    1996-01-01

    Purpose/Objective: To improve upon existing radioimmunotherapy (RAIT) approaches, we have devised a strategy to genetically induce high levels of new membrane-associated receptors on human cancer cells targetable by radiolabeled peptides. In this context, we report successful adenoviral-mediated transduction of tumor cells to express the murine gastrin releasing peptide receptor (mGRPr) as demonstrated by 125 I-labeled bombesin binding. Materials and Methods: To demonstrate the feasibility of our strategy and to provide rapid proof of principle, we constructed a plasmid encoding the mGRPr gene. We cloned the mGRPr gene into the adenoviral shuttle vector pACMVpLpARS+ (F. Graham). We then utilized the methodology of adenovirus-polylysine-mediated transfection (AdpLmGRPr) to accomplish transient gene expression of mGRPr in two human cancer cell lines including A427 non-small cell lung cancer cells and HeLa cervical cancer cells. Murine GRPr expression was then measured by a live-cell binding assay using 125 I-labeled bombesin. In order to develop this strategy further, it was necessary to construct a vector that would be more efficient for in vivo transduction. In this regard, we constructed a recombinant adenoviral vector (AdCMVGRPr) encoding the mGRPr under the control of the CMV promoter based on in vivo homologous recombination methods. The recombinant shuttle vector containing mGRPr was co-transfected with the adenoviral rescue plasmid pJM17 into the E1A trans complementing cell line 293 allowing for derivation of replication-incompetent, recombinant adenoviral vector. Individual plaques were isolated and subjected to two further rounds of plaque purification. The identity of the virus was confirmed at each step by PCR employing primers for mGRPr. The absence of wild-type adenovirus was confirmed by PCR using primers to the adenoviral E1A gene. SKOV3.ip1 human ovarian cancer cells and MDA-MB-231 human breast cancer cells were transduced in vitro with AdCMVGRPr at

  9. A radiolabeled peptide ligand of the hERG channel, [125I]-BeKm-1

    DEFF Research Database (Denmark)

    Angelo, Kamilla; Korolkova, Yuliya V; Grunnet, Morten

    2003-01-01

    The wild-type scorpion toxin BeKm-1, which selectively blocks human ether-a-go-go related (hERG) channels, was radiolabeled with iodine at tyrosine 11. Both the mono- and di-iodinated derivatives were found to be biologically active. In electrophysiological patch-clamp recordings mono-[127I]-BeKm-1...... had a concentration of half-maximal inhibition (IC50 value) of 27 nM, while wild-type BeKm-1 inhibited hERG channels with an IC50 value of 7 nM. Mono-[125I]-BeKm-1 was found to bind in a concentration-dependent manner and with picomolar affinity to hERG channel protein in purified membrane vesicles...... of [125I]-BeKm-1 to the hERG channel to an IC50 of 7 nM. In autoradiographic studies on rat hearts, binding of [125I]-BeKm-1 was dose-dependent and could partially be displaced by the addition of excess amounts of non-radioactive BeKm-1. The density of the radioactive signal was equally distributed...

  10. Imaging the adrenal glands with radiolabeled inhibitors of enzymes: concise communication

    International Nuclear Information System (INIS)

    Beierwaltes, W.H.; Wieland, D.M.; Mosley, S.T.; Swanson, D.P.; Sarkar, S.D.; Freitas, J.E.; Thrall, J.H.; Herwig, K.R.

    1978-01-01

    Although radioiodinated cholesterols furnished the first noninvasive imaging of the adrenal glands, it would be desirable to decrease the time for imaging and decrease the radiation dose. The relative tissue distributions of two radiolabeled enzyme inhibitors [ 3 H] metyrapol and 1-125-SKF-12185 were studied in dogs and man. Their percentage uptakes and target-to-nontarget ratios were similar. The adrenals of three dogs were imaged sharply at 2 hr after injection with 4-6 mCi of I-131-SKF-12185, confirmed by subsequent imaging with 1 mCi of I-131-6-beta-19-nor cholesterol at 5 days after injection. The use of 1 mCi of I-123-SKF will pemit imaging of the adrenals in 1-2 hr and will decrease the radiation dose in the human to 0.76 rads to the adrenal, 0.18 rads to the ovaries and 1.7 rads to the liver

  11. Mammalian Cell Culture Clarification: A Case Study Using Chimeric Anti-CEA Monoclonal Antibodies

    Directory of Open Access Journals (Sweden)

    Mohamed Ali Abol Hassan

    2011-12-01

    Full Text Available The extracellular expression of monoclonal antibodies (mAbs in mammalian cell culture provides both opportunities and restrictions for the design of robust harvest and clarification operations. With advances in cell culture media and cell lines, it is now possible to achieve high titers of over 5 g/l for mAbs. However, Mammalian cells are sensitive to breakage due to shear stress that can result in release of proteases and other host cell proteins (HCPs which eventually affects product stability and purity. There is larger number of mAbs undergoing clinical development and it has placed significant importance on platform technologies of process development. Generally, Centrifugation and microfiltration are the primary harvest techniques used in the industry and depth filtration is also used as a step operation on clarification. This study compares the unit operations; centrifugation, microfiltration and depth filtration for maximum recovery of monoclonal antibodies. The results have shown that the depth filtration as more suitable operation for mammalian cell culture clarification since it gives 96% recovery of mAbs in comparison to centrifugation and microfiltration. ABSTRAK: Pengungkapan luar sel dari antibodi monoklon (monoclonal antibodies ((mAbs dalam kultur sel mamalia memberi ruang dan batasan terhadap reka bentuk penuaian yang cekap dan penerangan operasi. Dengan kemajuan dalam media sel kultur dan cell lines (produk yang berupa sel kekal yang digunakan untuk tujuan kajian biologi, kini adalah berkemungkinan untuk memperolehi titer tinggi melebihi 5g/l untuk mAbs [2]. Walaupun begitu, sel mamalia sensitif terhadap retakan disebabkan tegasan ricih yang menyebabkan pengeluaran protease dan hos sel protein yang lain, (host cell proteins (HCPs akhirnya mempengaruhi kestabilan dan keaslian produk. Terdapat mAbs dalam jumlah besar yang masih menjalani pembangunan klinikal dan sesungguhnya ini penting sebagai satu landasan teknologi dalam proses pembangunan. Umumnya pengemparan dan mikropenurasan merupakan teknik asas tuaian dalam industri dan penurasan dalam juga digunakan sebagai satu pengendalian langkah dalam penjelasannya. Kajian ini membandingkan operasi unit: pengemparan, mikropenurasan dan penurasan dalam untuk perolehan antibodi monoklon yang maksima. Keputusan menunjukkan penurasan dalam adalah operasi yang lebih sesuai untuk penjelasan kultur sel mamalia kerana ia memberikan perolehan 96 % mAbs berbandingkan dengan cara pengemparan dan mikropenurasan.

  12. Origin of urinary nonconjugated 19-nor-deoxycorticosterone and metabolism of infused radiolabeled 19-nor-deoxycorticosterone in men and women

    International Nuclear Information System (INIS)

    Casey, M.L.; Guerami, A.; Milewich, L.; Gomez-Sanchez, C.E.; MacDonald, P.C.

    1985-01-01

    It is known that 19-nor-deoxycorticosterone (19-nor-DOC) is a potent mineralocorticosteroid that is present in urine of rats and humans in a free, i.e., nonconjugated, form. In the present investigation, the authors evaluated the metabolism of intravenously infused [ 3 H]19-nor-DOC and the possibility that 19-nor-DOC was formed from plasma DOC. They found that the metabolism of [ 3 H]19-nor-DOC infused intravenously in men and women was similar to that of DOC with important exceptions. The majority of the radiolabeled urinary metabolites of intravenously infused [ 3 H]19-nor-DOC were excreted in urine as glucuronosides. Little radioactivity, infused as [ 3 H]19-nor-DOC, was recovered in urine as nonconjugated or sulfoconjugated steroids. There was no free radiolabeled 19-nor-DOC in urine after the simultaneous infusion of [ 3 H]19-nor-DOC and [ 14 C]DOC. A major metabolite of [ 3 H]19-nor-DOC in urine was 19-nor-DOC-21-glucuronoside, whereas little or no intravenously infused radiolabeled DOC was excreted as radiolabeled DOC-glucuronoside. They also found that intravenously infused [ 14 C]DOC was not converted to urinary [ 14 C]19-nor-DOC (glucuronoside) and that other tritium-labeled metabolites of infused [ 3 H]19-nor-DOC contained no carbon-14. These findings are supportive of the proposition that free urinary 19-nor-DOC is not formed from plasma DOC; it may be formed in kidney from a precursor other than DOC or it may be formed nonenzymatically in kidney or urine from a precursor such as 19-oic-DOC

  13. 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

  14. 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.

  15. 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)

  16. 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

  17. Diagnostic imaging of herpes simplex virus encephalitis using a radiolabeled antiviral drug: autoradiographic assessment in an animal model

    International Nuclear Information System (INIS)

    Saito, Y.; Rubenstein, R.; Price, R.W.; Fox, J.J.; Watanabe, K.A.

    1984-01-01

    To develop a new approach to the diagnosis of herpes simplex encephalitis, we used a radiolabeled antiviral drug, 2'-fluoro-5-methyl-1-beta-D-arabinosyluracil labeled with carbon 14 ([14C]FMAU), as a probe for selectively imaging brain infection in a rat model by quantitative autoradiography. A high correlation was found between focal infection, as defined by immunoperoxidase viral antigen staining, and increased regional [14C]FMAU uptake in brain sections. Two potential sources of false-positive imaging were defined: high concentrations of drug in the choroid plexus because of its higher permeability compared with brain, and drug sequestration by proliferating uninfected cell populations. Our results support the soundness of the proposed strategy of using a labeled antiviral drug that is selectively phosphorylated by herpes simplex virus type 1 thymidine kinase in conjunction with scanning methods for human diagnosis, and also define some of the factors that must be taken into account when planning clinical application

  18. 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

  19. 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)

  20. 68Ga-THP-PSMA: A PET Imaging Agent for Prostate Cancer Offering Rapid, Room-Temperature, 1-Step Kit-Based Radiolabeling.

    Science.gov (United States)

    Young, Jennifer D; Abbate, Vincenzo; Imberti, Cinzia; Meszaros, Levente K; Ma, Michelle T; Terry, Samantha Y A; Hider, Robert C; Mullen, Greg E; Blower, Philip J

    2017-08-01

    The clinical impact and accessibility of 68 Ga tracers for the prostate-specific membrane antigen (PSMA) and other targets would be greatly enhanced by the availability of a simple, 1-step kit-based labeling process. Radiopharmacy staff are accustomed to such procedures in the daily preparation of 99m Tc radiopharmaceuticals. Currently, chelating agents used in 68 Ga radiopharmaceuticals do not meet this ideal. The aim of this study was to develop and evaluate preclinically a 68 Ga radiotracer for imaging PSMA expression that could be radiolabeled simply by addition of 68 Ga generator eluate to a cold kit. Methods: A conjugate of a tris(hydroxypyridinone) (THP) chelator with the established urea-based PSMA inhibitor was synthesized and radiolabeled with 68 Ga by adding generator eluate directly to a vial containing the cold precursors THP-PSMA and sodium bicarbonate, with no further manipulation. It was analyzed after 5 min by instant thin-layer chromatography and high-performance liquid chromatography. The product was subjected to in vitro studies to determine PSMA affinity using PSMA-expressing DU145-PSMA cells, with their nonexpressing analog DU145 as a control. In vivo PET imaging and ex vivo biodistribution studies were performed in mice bearing xenografts of the same cell lines, comparing 68 Ga-THP-PSMA with 68 Ga-HBED-CC-PSMA. Results: Radiolabeling was complete (>95%) within 5 min at room temperature, showing a single radioactive species by high-performance liquid chromatography that was stable in human serum for more than 6 h and showed specific binding to PSMA-expressing cells (concentration giving 50% inhibition of 361 ± 60 nM). In vivo PET imaging showed specific uptake in PSMA-expressing tumors, reaching 5.6 ± 1.2 percentage injected dose per cubic centimeter at 40-60 min and rapid clearance from blood to kidney and bladder. The tumor uptake, biodistribution, and pharmacokinetics were not significantly different from those of 68 Ga

  1. 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)

  2. 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)

  3. 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.

  4. 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.

  5. 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)

  6. 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

  7. 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.

  8. 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)

  9. 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.)

  10. Radiolabeling of rituximab with {sup 188}Re and {sup 99m}Tc using the tricarbonyl technology

    Energy Technology Data Exchange (ETDEWEB)

    Dias, Carla Roberta [Instituto de Pesquisas Energeticas e Nucleares, Av. Professor Lineu Prestes 2242, 05508-000 Sao Paulo (Brazil); Jeger, Simone [Center for Radiopharmaceutical Sciences ETH-PSI-USZ, Paul Scherrer Institute, 5232 Villigen-PSI (Switzerland); Osso, Joao Alberto [Instituto de Pesquisas Energeticas e Nucleares, Av. Professor Lineu Prestes 2242, 05508-000 Sao Paulo (Brazil); Mueller, Cristina; De Pasquale, Christine; Hohn, Alexander; Waibel, Robert [Center for Radiopharmaceutical Sciences ETH-PSI-USZ, Paul Scherrer Institute, 5232 Villigen-PSI (Switzerland); Schibli, Roger, E-mail: roger.schibli@psi.c [Center for Radiopharmaceutical Sciences ETH-PSI-USZ, Paul Scherrer Institute, 5232 Villigen-PSI (Switzerland); Department of Chemistry and Applied Biosciences of the ETH, 8093 Zurich (Switzerland)

    2011-01-15

    Introduction: The most successful clinical studies of immunotherapy in patients with non-Hodgkin's lymphoma (NHL) use the antibody rituximab (RTX) targeting CD20{sup +} B-cell tumors. Rituximab radiolabeled with {beta}{sup -} emitters could potentiate the therapeutic efficacy of the antibody by virtue of the particle radiation. Here, we report on a direct radiolabeling approach of rituximab with the {sup 99m}Tc- and {sup 188}Re-tricarbonyl core (IsoLink technology). Methods: The native format of the antibody (RTX{sub wt}) as well as a reduced form (RTX{sub red}) was labeled with {sup 99m}Tc/{sup 188}Re(CO){sub 3}. The partial reduction of the disulfide bonds to produce free sulfhydryl groups (-SH) was achieved with 2-mercaptoethanol. Radiolabeling efficiency, in vitro human plasma stability as well as transchelation toward cysteine and histidine was investigated. The immunoreactivity and binding affinity were determined on Ramos and/or Raji cells expressing CD20. Biodistribution was performed in mice bearing subcutaneous Ramos lymphoma xenografts. Results: The radiolabeling efficiency and kinetics of RTX{sub red} were superior to that of RTX{sub wt} ({sup 99m}Tc: 98% after 3 h for RTX{sub red} vs. 70% after 24 h for RTX{sub wt}). {sup 99m}Tc(CO){sub 3}-RTX{sub red} was used without purification for in vitro and in vivo studies whereas {sup 188}Re(CO){sub 3}-RTX{sub red} was purified to eliminate free {sup 188}Re-precursor. Both radioimmunoconjugates were stable in human plasma for 24 h at 37{sup o}C. In contrast, displacement experiments with excess cysteine/histidine showed significant transchelation in the case of {sup 99m}Tc(CO){sub 3}-RTX{sub red} but not with pre-purified {sup 188}Re(CO){sub 3}-RTX{sub red}. Both conjugates revealed high binding affinity to the CD20 antigen (K{sub d}=5-6 nM). Tumor uptake of {sup 188}Re(CO){sub 3}-RTX{sub red} was 2.5 %ID/g and 0.8 %ID/g for {sup 99m}Tc(CO){sub 3}-RTX{sub red} 48 h after injection. The values for other

  11. (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%....

  12. Radiopharmaceuticals in positron emission tomography: Radioisotope productions and radiolabelling procedures at the Austin and Repatriation Medical Centre

    Energy Technology Data Exchange (ETDEWEB)

    Tochon-Danguy, H.J.; Sachinidis, J.I.; Chan, J.G.; Cook, M. [Austin and Repatriation Medical Centre, Melbourne, VIC (Australia). Centre for Positron Emission Tomography

    1997-10-01

    Positron Emission Tomography (PET) is a technique that utilizes positron-emitting radiopharmaceuticals to map the physiology, biochemistry and pharmacology of the human body. Positron-emitting radioisotopes produced in a medical cyclotron are incorporated into compounds that are biologically active in the body. A scanner measures radioactivity emitted from a patient`s body and provides cross-sectional images of the distribution of these radiolabelled compounds in the body. It is the purpose of this paper to review the variety of PET radiopharmaceuticals currently produced at the Austin and Repatriation Medical Centre in Melbourne. Radioisotope production, radiolabelling of molecules and quality control of radiopharmaceuticals will be discussed. A few examples of their clinical applications will be shown as well. During the last five years we achieved a reliable routine production of various radiopharmaceuticals labelled with the four most important positron-emitters: oxygen-15 (t,{sub 1/2}=2min), nitrogen-13 (t{sub 1/2}= 10 min), carbon-11 (t{sub 1/2}=20 min) and fluorine-18 (t{sub 1/2}= 110 min). These radiopharmaceuticals include [{sup 15}O]oxygen, [{sup 15}O]carbon monoxide, [{sup 15}O]carbon dioxide, [{sup 15}O]water, [{sup 13}N]ammonia, [{sup 11}C]flumazenil, [{sup 11}C]SCH23390, [{sup 18}F]fluoromisonidazole and [{sup 18}F]fluoro-deoxy-glucose ([{sup 18}F]FDG). In addition, since the half life of [{sup 18}F] is almost two hours, regional distribution can be done, and the Austin and Repatriation Medical Centre is currently supplying [{sup 18}F]FDG in routine to other hospitals. Future new radiopharmaceuticals development include a [{sup 18}F]thymidine analog to measure cell proliferation and a [{sup 11}C]pyrroloisoquinoline to visualize serotonergic neuron abnormalities. (authors) 23 refs., 2 tabs.

  13. Radiopharmaceuticals in positron emission tomography: Radioisotope productions and radiolabelling procedures at the Austin and Repatriation Medical Centre

    International Nuclear Information System (INIS)

    Tochon-Danguy, H.J.; Sachinidis, J.I.; Chan, J.G.; Cook, M.

    1997-01-01

    Positron Emission Tomography (PET) is a technique that utilizes positron-emitting radiopharmaceuticals to map the physiology, biochemistry and pharmacology of the human body. Positron-emitting radioisotopes produced in a medical cyclotron are incorporated into compounds that are biologically active in the body. A scanner measures radioactivity emitted from a patient's body and provides cross-sectional images of the distribution of these radiolabelled compounds in the body. It is the purpose of this paper to review the variety of PET radiopharmaceuticals currently produced at the Austin and Repatriation Medical Centre in Melbourne. Radioisotope production, radiolabelling of molecules and quality control of radiopharmaceuticals will be discussed. A few examples of their clinical applications will be shown as well. During the last five years we achieved a reliable routine production of various radiopharmaceuticals labelled with the four most important positron-emitters: oxygen-15 (t, 1/2 =2min), nitrogen-13 (t 1/2 = 10 min), carbon-11 (t 1/2 =20 min) and fluorine-18 (t 1/2 = 110 min). These radiopharmaceuticals include [ 15 O]oxygen, [ 15 O]carbon monoxide, [ 15 O]carbon dioxide, [ 15 O]water, [ 13 N]ammonia, [ 11 C]flumazenil, [ 11 C]SCH23390, [ 18 F]fluoromisonidazole and [ 18 F]fluoro-deoxy-glucose ([ 18 F]FDG). In addition, since the half life of [ 18 F] is almost two hours, regional distribution can be done, and the Austin and Repatriation Medical Centre is currently supplying [ 18 F]FDG in routine to other hospitals. Future new radiopharmaceuticals development include a [ 18 F]thymidine analog to measure cell proliferation and a [ 11 C]pyrroloisoquinoline to visualize serotonergic neuron abnormalities. (authors)

  14. Circulating immune complexes in the serum in systemic lupus erythematosus and in carriers of hepatitis B antigen: quantitation by binding to radiolabeled Cl/sub q/

    International Nuclear Information System (INIS)

    Nydegger, U.E.; Lambert, P.H.; Gerber, H.; Miescher, P.A.

    1974-01-01

    A sensitive and reproducible procedure fr the detection of souble immune complexes in sera from patients with various immunopathological disorders is reported. Radiolabeled Clq is reacted with sera containing immune complexes. Separation of free from complex bound [ 125 I]Clq is achieved by selective precipitation with polyethylene glycol (PEG). The minimal amount of aggregated immunoglobulins thus detected is about 10 μg and that of soluble human IgG-anti-IgG complexes is about 3 μg of complexed antibody. Some immune complexes formed in large antigen excess (Ag 2 Ab) can still be detected by this radiolabeled Clq bining assay. In a second step, this radiolabeled Clq binding assay was applied to an experimental model of immune complex disease and was shown to be efficient for the detection of in vivo formed immune complexes. Finally, the technique could be applied to the study of sera from patients with systemic lupus erythematosus (SLE) or to carriers of the Hepatitis B antigen (HB-Ag). Particularly high values were seen in active disease, a finding which was confirmed by follow-up studies performed with four SLE patients. No increased [ 125 I]Clq binding was seen in 18 healthy carriers of the HB-Ag; whereas, sera from carriers with hepatitis appear to precipitate increased [ 125 I]Clq percentages: 7/24 cases with acute transient and 4/7 cases with chronic persistent hepatitis were found to increasingly bind [ 125 I]Clq. The results were also used for a correlative study of [ 125 I]Clq binding to IgG levels in the sera but increased [ 125 I]Clq binding could not be attributed to high serum IgG levels which are likely to account for the evaluation of immune complex diseases in human pathology. (U.S.)

  15. 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

  16. 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

  17. 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...

  18. 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

  19. 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

  20. 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.)

  1. 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

  2. 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)

  3. 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.

  4. 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).

  5. 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)

  6. 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.)

  7. 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

  8. Radiolabeling of HTE1PA: A new monopicolinate cyclam derivative for Cu-64 phenotypic imaging. In vitro and in vivo stability studies in mice

    International Nuclear Information System (INIS)

    Frindel, Mathieu; Camus, Nathalie; Rauscher, Aurore; Bourgeois, Mickaël; Alliot, Cyrille; Barré, Louisa; Gestin, Jean-François; Tripier, Raphaël; Faivre-Chauvet, Alain

    2014-01-01

    Introduction: HTE1PA, a monopicolinate-N-alkylated cyclam-based ligand has previously demonstrated fast complexation process, high kinetic inertness and important thermodynamic and electrochemical stability with respect to natural copper. In this work we first developed a new synthetic route to obtain HTE1PA in good yields. Then, we investigated HTE1PA chelation properties towards copper-64 and assessed in vitro and in vivo stability of the resulting compound. Methods: Radiolabeling of HTE1PA with copper-64 was tested at different ligand concentrations in ammonium acetate medium. In vitro stability study was carried out by incubating [ 64 Cu]TE1PA complex in human serum at both 37 °C and 4 °C; chromatographic controls were performed over 24 h. Biodistribution, pharmacokinetic and hepatic metabolism of [ 64 Cu]TE1PA were conducted in BALC/c mice in comparison with [ 64 Cu]acetate and [ 64 Cu]DOTA, used as a reference ligand. Results: The promising results obtained for natural copper complexation were confirmed. HTE1PA was quantitatively radiolabeled in 15 min at room temperature. The resulting complex showed high serum stability. [ 64 Cu]TE1PA induced a significant uptake in the liver and kidneys at early biodistribution time point. Nevertheless, a high speed wash out was observed at 24 h leading to significantly lower uptake into the liver compared to [ 64 Cu]DOTA. The metabolism study was consistent with a high resistance to transchelation as the initial uptake into liver matches with the intact form of [ 64 Cu]TE1PA. Conclusion: Despite the partial elimination of HTE1PA – as copper-64 complex – through the hepatic route, its high selectivity for copper and its resistance to transchelation make it a promising ligand for antibody radiolabeling with either copper-64 or copper-67

  9. 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

  10. 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.

  11. In vivo and in vitro evaluation of dota-lanreotide radiolabelled with gallium-67

    International Nuclear Information System (INIS)

    Aldegheri, Eliane Bernardes

    2005-01-01

    One of the refinements of modern Nuclear Medicine is the capacity of providing dynamic and kinetics images of the administered radiopharmaceutical, reproducing its transport mechanism, action sites, receptor binding and excretion route. With the continues technological advances new radiopharmaceuticals have been developed in order to express higher specificity and with higher characters of affinity between receptor/complex. One radiopharmaceutical is formed by a reagent or bio molecule that has in its structure a radioisotope, that has the objectives of carrying it to the organs of affinity or to benign or malign tumoral process. Somatostatin inhibits the growing and proliferation of several tumoral cells. Somatostatin analogs bind to somatostatic receptors that are expressed in different kind of neoplasia DOTA-LANREOTIDE (DOTALAN) is an octapeptide analog to somatostatin. The interest of labeling the bio conjugate with gallium-67 in Nuclear Medicine comes from its physical, chemical and biological properties. Besides its gamma radiation, useful in the diagnosis of inflammation and infection foci, 67 Ga emits Auger electrons (0.1 - 8 keV) and conversion electrons (80 - 90 keV), making it attractive to internal radiotherapy if the vectors used to lead the radionuclide to the tumoral cell are internalized. The objective of this work was to develop a methodology of labelling DOTA-LANREOTIDE with 67 Ga, optimizing the labelling variables and its quality control. The novelty aspect was the comparison between labeling with national and imported 67 Ga, in its original and purified forms. The purification of 67 Ga was essential to reach yields higher than 90%. The radiolabelled bio conjugate peptides must be free of metallic contaminants that could compete in the labeling process. The following procedure was established after studying the labeling parameters: mass of peptide of 10 μg (6nmol), pH5, final reaction volume of 170 μL of the labelled and 67 Ga activity of 222

  12. WE-G-303-04: Intrinsically Radiolabeled Nanoparticles: An Emerging Paradigm

    Energy Technology Data Exchange (ETDEWEB)

    Cai, W. [University of Wisconsin-Madison (United States)

    2015-06-15

    Over the last decade, there has been a growing interest in applying nanotechnology to cancer detection, treatment, and treatment monitoring. Advances in nanotechnology have enabled the fabrication of nanoparticles from various materials with different shapes and sizes. Nanoparticles can be accumulated preferentially within tumors by either “passive targeting” through a phenomenon typically known as “enhanced permeability and retention” or “active targeting” in which nanoparticles are conjugated with antibodies or peptides directed against tumor and/or stromal markers. The tumor specificity of nanoparticles in conjunction with their unique physicochemical properties offers many novel strategies for cancer treatment and detection. For example, notable approaches in the radiation oncology setting include the use of gold nanoparticles for radiation response modulation of tumor or normal tissue and thermal ablation or hyperthermia treatment of tumors. Some of these approaches are currently being tested either on humans or on animals and, very likely, will become the clinical reality in the near future. Various computational and experimental techniques have also been applied to address unique research issues associated with nanoparticles and may become the standard tools for future investigations and clinical translations. Therefore, both clinicians and researchers may need to be properly educated about the basic principles as well as the promise of nanoparticle-based applications with regard to the future of cancer diagnostics and therapeutics. This symposium will familiarize the audience with the potential applications of nanoparticles in oncologic imaging and therapy using specific illustrative examples. The audience will be properly oriented by these illustrative examples to the multiple avenues for collaborative research amongst interdisciplinary teams of physicists, clinicians, engineers, chemists, and biologists in industry and academia. Learning

  13. Radiohalogenation of biomolecules. An experimental study on radiohalogen preparation, precursor synthesis, radiolabeling and biodistribution

    International Nuclear Information System (INIS)

    Koziorowski, J.

    1998-01-01

    Radiohalogens are widely used in nuclear medicine, both as tool for diagnostic in vivo imaging, and in radionuclide therapy. This study deals with the use of radiohalogens; separation, precursor synthesis, labeling and biological behavior. The focus is on 211 At and 124 I, the former being a candidate for nuclide therapy and the latter potentially useful for diagnostic imaging and Auger-electron based radiotherapy. For astatine the separation, labeling and some biological behavior is described, and for iodine the latter two. Astatine was separated from an irradiated bismuth target by dry distillation. A novel cryotrap was developed for the isolation of astatine and subsequent synthesis of radiolabeled compounds. 5-[ 211 At]astato-2'-deoxyuridine (AUdR) and N-succinimidyl-4-[ 211 At]astatobenzoate (SAB) were synthesized in 95% respectively 90% radiochemical yields. The former is incorporated into DNA of proliferating cells and can therefore be used as an endoradiotherapeutic agent. The latter is a conjugate for the astatination of proteins. Human epidermal growth factor (hEGF) was tagged with astatine using three approaches: a) direct labeling of native hEGF, b) conjugation with SAB, and c) direct labeling of an hEGF - 7-(3-aminopropyl)-7,8-dicarba-nido-undecaborate(1-) conjugate. The overall labeling yields were 3.5% for direct labeling, 44% for SAB and 70% for the hEGF-nido-carborane conjugate. A new route to N-succinimidyl 3- and 4- [ 124 I]iodobenzoate, two reagents for radioiodination of proteins is described affording 90% radiochemical yield. Three radioiodinated analogs of PK11195, 1-(2-chlorophenyl)-N-methyl-N-(1-methylpropyl)isoquinoline-3-carboxyam ide, a peripheral-type benzodiazepine receptor antagonist, were synthesized. All three analogs were obtained in >90% radiochemical yield. Synthesis and application of 5-[ 124 I]iodo-2'-deoxyuridine (IUdR) is presented. The closo-dodecaborate anion was evaluated as prosthetic group for radioiodination of

  14. WE-G-303-04: Intrinsically Radiolabeled Nanoparticles: An Emerging Paradigm

    International Nuclear Information System (INIS)

    Cai, W.

    2015-01-01

    Over the last decade, there has been a growing interest in applying nanotechnology to cancer detection, treatment, and treatment monitoring. Advances in nanotechnology have enabled the fabrication of nanoparticles from various materials with different shapes and sizes. Nanoparticles can be accumulated preferentially within tumors by either “passive targeting” through a phenomenon typically known as “enhanced permeability and retention” or “active targeting” in which nanoparticles are conjugated with antibodies or peptides directed against tumor and/or stromal markers. The tumor specificity of nanoparticles in conjunction with their unique physicochemical properties offers many novel strategies for cancer treatment and detection. For example, notable approaches in the radiation oncology setting include the use of gold nanoparticles for radiation response modulation of tumor or normal tissue and thermal ablation or hyperthermia treatment of tumors. Some of these approaches are currently being tested either on humans or on animals and, very likely, will become the clinical reality in the near future. Various computational and experimental techniques have also been applied to address unique research issues associated with nanoparticles and may become the standard tools for future investigations and clinical translations. Therefore, both clinicians and researchers may need to be properly educated about the basic principles as well as the promise of nanoparticle-based applications with regard to the future of cancer diagnostics and therapeutics. This symposium will familiarize the audience with the potential applications of nanoparticles in oncologic imaging and therapy using specific illustrative examples. The audience will be properly oriented by these illustrative examples to the multiple avenues for collaborative research amongst interdisciplinary teams of physicists, clinicians, engineers, chemists, and biologists in industry and academia. Learning

  15. 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)

  16. 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.

  17. 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

  18. 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

  19. 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

  20. 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.

  1. 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.

  2. 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.

  3. 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

  4. 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)

  5. Synthesis of radiolabeled racemic and enanthiomeric antiarrhythmic agents

    International Nuclear Information System (INIS)

    Hsi, R.S.P.; Stolle, W.T.; Stelzer, L.S.; Hester, J.B.; Perricone, S.C.

    1992-01-01

    Ventricular fibrillation is a leading cause of fatality in patients suffering from cardiovascular disorders. Among approaches to treating cardiac dysrhythmia with medicinal agents is the use of compounds categorized as open-quotes Class IIIclose quotes antiarrhythmic agents to prolong cardiac action potential and increase the refractoriness of cardiac tissues without affecting the sodium current. Investigations into structural requirements necessary for such biological activities led to the synthesis of a series of aniline-propanolamine derivatives. This report describes the preparation of carbon-14 and tritium labeled forms of racemic and enantiomeric forms of these derivatives for conducting drug disposition studies in test animals and human subjects

  6. Studies of the radiolabeling and biodistribution of substance P using lutetium-177 as a radiotracer; Estudo da marcacao e biodistribuicao da substancia P utilizando lutecio-177 como radiotracador

    Energy Technology Data Exchange (ETDEWEB)

    Lima, Clarice Maria de

    2011-07-01

    Malignant gliomas are primary brain tumors, resistant to various treatments, as chemotherapy, radiotherapy, induction of apoptosis and surgery. An alternative for the treatment of malignant gliomas is the radionuclide therapy. This technique apply radiolabeled molecules that selectively bind to tumor cells producing cytotoxic effect by dose irradiation, and resulting in death of tumor cells. Most protocols for radionuclide therapy of malignant brain tumors involve the administration of peptides labeled with {beta}{sup -} emitting radioisotopes. The Substance P (SP) is an 11- amino acid neuropeptide, characterized by the C-terminal sequence Phe-X-Gly-Leu-Met-NH{sub 2}. The use of SP labeled with different radionuclides including {sup 177}Lu, have been proposed for in vivo treatment of tumors. SP is the most important target of neurokinin 1 receptors, over expressed in malignant gliomas. The objective of this work was to study conditions of radiolabeling DOTA-SP with {sup 177}Lu, the stability of labeled compound and in vivo and in vitro, to develop a protocol production and evaluate the potential of the radiopharmaceutical in the therapy of gliomas. The labeling conditions were optimized varying the temperature, reaction time, activity of lutetium-177 chloride and mass of DOTA-SP. The radiochemical purity of preparations were analyzed by chromatographic techniques. The stability of {sup 17L}u -DOTA- SP radiolabeled with low activity of {sup 177}Lu was evaluated for different time at 2-8 degree C or incubated in human serum. The stability of the labeled with high activity of {sup 177}Lu was also analyzed in the presence of gentisic acid (6 mg / mL) added after the labeling reaction. The labeled conditions in low and high activity were subjected to evaluation for the ability to cause oxidation of methionine residue, adding the D-L- methionine amino acid to the reaction medium (6 mg / mL) and subsequent chromatographic evaluation. In vitro study with {sup 177}Lu

  7. 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.)

  8. 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.

  9. 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.)

  10. 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

  11. 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...

  12. 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)

  13. 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.)

  14. 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

  15. 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.)

  16. 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)

  17. N-hydroxysuccinimide-hippuran ester: application for radiolabeling of macromolecules

    International Nuclear Information System (INIS)

    Chervu, L.R.; Chun, S.B.; Bhargava, K.K.

    1987-01-01

    A method for synthesis of N-hydroxysuccinimide ester of radioactive orthoiodohippurric acid (OIH-OSU) is developed in order to label macromolecules including antibodies. The OIH-OSU is prepared in 87% yield by reacting molar equivalents of o-iodohippuric acid, N:N-di-succinimidyl carbonate and pyridine in DMF overnight. The active labeled ester is obtained using high specific activity OIH in a similar synthetic protocol. Conjugation of OIH-OSU to human serum albumin is effected by incubating the reactants for half an hour at room temperature followed by purification of the labeled protein on a Sephadex G-100 column with activity yield of 44.3%. Organ distribution for the labeled albumin preparation and the commercial iodinated human serum albumin (RISA) in mice and rats is similar. As expected urinary excretion of radioactivity for the labeled preparation is greater than that of RISA reflecting the rapid urinary clearance of the OIH moiety released into the bloodstream. Hippuran labeling method offers a mild and rapid protocol for radioiodine labeling of proteins and antibodies for application in diagnostic nuclear medicine procedures

  18. 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.)

  19. 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.

  20. 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

  1. 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

  2. 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.

  3. 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)

  4. 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.

  5. 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

  6. 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

  7. 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

  8. 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)

  9. 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)

  10. Evaluation of new radiopharmaceuticals: synthesis, evaluation, and biodistribution of radiolabelled peptide of VCAM-1 and αvβ3

    International Nuclear Information System (INIS)

    Ardisson, V.

    2006-07-01

    The new development of nuclear medicine implies the search of new isotopes but also for new vectors specific of functions or metabolic pathways. We investigated new radiopharmaceuticals intended for new diagnostic approaches of two physiopathological mechanisms frequently met in our populations: the atherosclerosis vulnerable plaque and the tumor angio genesis. We studied and optimized the iodine and 99 m-technetium radiolabelling, of a series of peptides in order to allow the in vivo use of these tracers for imaging studies in animals and possibly in humans. The radioiodination, was carried out by electrophilic substitution, and technetium was linked by a tri-carbonyl B.F.C.A. (Isolink). The reaction parameters were defined so that the labelling reactions presents a high radiochemical purity (>95%), and a high specificity activity. The reactions are fast and reproducible. Various physicochemical properties: lipo-solubility, stability of labelling, and pharmacokinetic properties: non specific binding, metabolization and organ biodistribution of peptides in animal model, were studied. These results indicate which peptide may be a suitable candidate for targeting trials. (author)

  11. Diagnostic and therapeutic perspectives in nuclear medicine: radiolabelled biomolecules; Perspectivas diagnosticas y terapeuticas en medicina nuclear: biomoleculas radiomarcadas

    Energy Technology Data Exchange (ETDEWEB)

    Ferro F, G. [Gerencia de Aplicaciones Nucleares en la Salud. ININ, 11801 Mexico D.F. (Mexico); Murphy, C.A. de; Pedraza L, M. [Departamento de Medicina Nuclear. Instituto Nacional de Ciencias Medicas y Nutricion Salvador Zubiran, Mexico D.F. (Mexico); Melendez A, L. [Facultad de Medicina, UAEM, 50000 Toluca, Estado de Mexico (Mexico)

    2003-07-01

    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)

  12. 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

  13. Diagnostic and therapeutic perspectives in nuclear medicine: radiolabelled biomolecules; Perspectivas diagnosticas y terapeuticas en medicina nuclear: biomoleculas radiomarcadas

    Energy Technology Data Exchange (ETDEWEB)

    Ferro F, G [Gerencia de Aplicaciones Nucleares en la Salud. ININ, 11801 Mexico D.F. (Mexico); Murphy, C.A. de; Pedraza L, M [Departamento de Medicina Nuclear. Instituto Nacional de Ciencias Medicas y Nutricion Salvador Zubiran, Mexico D.F. (Mexico); Melendez A, L [Facultad de Medicina, UAEM, 50000 Toluca, Estado de Mexico (Mexico)

    2003-07-01

    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)

  14. 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

  15. Regional deposition of mometasone furoate nasal spray suspension in humans.

    Science.gov (United States)

    Shah, Samir A; Berger, Robert L; McDermott, John; Gupta, Pranav; Monteith, David; Connor, Alyson; Lin, Wu

    2015-01-01

    Nasal deposition studies can demonstrate whether nasal sprays treating allergic rhinitis and polyposis reach the ciliated posterior nasal cavity, where turbinate inflammation and other pathology occurs. However, quantifying nasal deposition is challenging, because in vitro tests do not correlate to human nasal deposition; gamma scintigraphy studies are thus used. For valid data, the radiolabel must distribute, as the drug, into different-sized droplets, remain associated with the drug in the formulation after administration, and not alter its deposition. Some nasal deposition studies have demonstrated this using homogenous solutions. However, most commercial nasal sprays are heterogeneous suspensions. Using mometasone furoate nasal suspension (MFS), we developed a technique to validate radiolabel deposition as a surrogate for nasal cavity drug deposition and characterized regional deposition and nasal clearance in humans. Mometasone furoate (MF) formulation was spiked with diethylene triamine pentacaetic acid. Both unlabeled and radiolabeled formulations (n = 3) were sprayed into a regionally divided nasal cast. Drug deposition was quantified by high pressure liquid chromatography within each region; radiolabel deposition was determined by gamma camera. Healthy subjects (n = 12) were dosed and imaged for six hours. Scintigraphic images were coregistered with magnetic resonance imaging scans to quantify anterior and posterior nasal cavity deposition and mucociliary clearance. The ratio of radiolabel to unlabeled drug was 1.05 in the nasal cast and regionally appeared to match, indicating that in vivo radiolabel deposition could represent drug deposition. In humans, MFS delivered 86% (9.2) of metered dose to the nasal cavity, approximately 60% (9.1) of metered dose to the posterior nasal cavity. After 15 minutes, mucociliary clearance removed 59% of the initial radiolabel in the nasal cavity, consistent with clearance rates from the ciliated posterior surface. MFS

  16. Improvement of A.E.S System, using a 188Re-radiolabeled hapten

    International Nuclear Information System (INIS)

    Morandeau, L.

    2002-01-01

    Full text: Feasibility of two-step radioimmunotherapy (RIT) of cancer by the Affinity Enhancement System (AES) has been demonstrated in experimental and clinical studies. This technique, associating a bispecific antibody (BsAb) and a radiolabeled bivalent peptide, reduces toxicity and improves therapeutic efficacy of the treatment compared to the one step targeting method. The formation of a cyclic complex (antigen-BsAb- hapten-BsAb-antigen) observed on the tumor allows good tumoral fixation. This is associated with low non-specific uptake, due to the fast clearance of the hapten from the organism. Iodine 131, used currently in clinical applications, has however several disadvantages. These include the mean energy of □ . particles, strong y emission and long physical half-life. Rhenium-188 is the radionuclide of choice to replace iodine-131; its low cost, its availability from a W-188/Re-188 generator and its very favorable radiophysical properties (t 1/2 =16.9h; E□=2.118 MeV; Ey (15%)=155keV) make it a very interesting radionuclide for radioimmunotherapy applications. Unlike the case of iodine-131, the radiolabelling of the peptide by rhenium-188 requires the preliminary coupling of a bifunctional chelating agent. This ensures the formation of an in vivo stable complex with the radionuclide. The object of this post-doctoral project is to obtain a rhenium-188 radiolabeled bivalent hapten. To do this, a monovalent hapten will be coupled to a chelating agent that involves two or three patterns to complex the radionuclide, leading to a bivalent or trivalent radiolabeled hapten, suitable for applications in A.E.S. system. The monovalent hapten used, called HSGL (histaminosuccinylglycyllysine) is a small heteropeptide composed of a chain of four molecules which are histamine, succinic acid, glycine, lysine. It is recognised by the antibody anti-HSG. Two kinds of chelating agents, dithiocarbamates and dithiobenzoates will be studied. They have been synthesised at

  17. Radiolabelled multifunctional nanoparticles for targeted diagnostic and therapeutic applications in oncology

    International Nuclear Information System (INIS)

    Rangger, C.

    2013-01-01

    Nanoparticles, liposomes in particular, have gained great attention as easily engineerable nanoscale systems with distinct properties, offering an ideal platform for a variety of diagnostic and therapeutic applications. The aim of this PhD thesis was the design, synthesis as well as the in vitro and in vivo evaluation of several radiolabelled multifunctional liposomal nanoparticles for the targeted imaging of tumour cells and tumour-induced angiogenesis. Radiolabelling methods for different radionuclides were developed and the liposomes were functionalised with polyethylene glycol (PEG) to improve the pharmacokinetic profile. Targeting sequences such as the tripeptide Arg-Gly-Asp (RGD), the neuropeptide substance P (SP), the somatostatin analogue tyrosine-3-octreotide (TOC), and the vasoactive intestinal peptide (VIP) were tested for their applicability as tools for the targeted delivery of imaging agents. Finally, by the combination of two targeting sequences, namely RGD and SP, on one liposome multireceptor-targeting (hybrid-targeting) was investigated. These multifunctional vehicles were also functionalized with imaging labels for the detection and imaging of tumours by single photon emission computed tomography (SPECT), fluorescence microscopy as well as magnetic resonance (MR) imaging. The liposomes developed in this thesis showed multifunctional properties combining several imaging approaches with specific targeting for oncological applications. In vitro behaviour, e.g., receptor binding could be improved, resulting in optimised targeting shown both by the radiolabel and fluorescent label. However, the in vivo properties, especially the tumour targeting characteristics remained suboptimal, revealing the challenges of targeting approaches in nanoscience. Nonetheless, these results brought important insights for the development and optimisation of multifunctional nanocarriers. (author) [de

  18. Effect of glycosylation on biodistribution of radiolabeled glucagon-like peptide 1

    International Nuclear Information System (INIS)

    Watanabe, Ayahisa; Nishijima, Ken-ichi; Zhao, Songji; Tamaki, Nagara; Kuge, Yuji; Tanaka, Yoshikazu; Itoh, Takeshi; Takemoto, Hiroshi

    2012-01-01

    Glycosylation is generally applicable as a strategy for increasing the activity of bioactive proteins. In this study, we examined the effect of glycosylation on biodistribution of radiolabeled glucagon-like peptide 1 (GLP-1) as a bioactive peptide for type 2 diabetes. Noninvasive imaging studies were performed using a gamma camera after the intravenous administration of 123 I-GLP-1 or 123 I-α2, 6-sialyl N-acetyllactosamine (glycosylated) GLP-1 in rats. In ex vivo biodistribution studies using 125 I-GLP-1 or 125 I-glycosylated GLP-1, organ samples were measured for radioactivity. Plasma samples were added to 15% trichloroacetic acid (TCA) to obtain TCA-insoluble and TCA-soluble fractions. The radioactivity in the TCA-insoluble and TCA-soluble fractions was measured. In the noninvasive imaging studies, a relatively high accumulation level of 123 I-GLP-1 was found in the liver, which is the major organ to eliminate exogenous GLP-1. The area under the time-activity curve (AUC) of 123 I-glycosylated GLP-1 in the liver was significantly lower (89%) than that of 123 I-GLP-1. These results were consistent with those of ex vivo biodistribution studies using 125 I-labeled peptides. The AUC of 125 I-glycosylated GLP-1 in the TCA-insoluble fraction was significantly higher (1.7-fold) than that of GLP-1. This study demonstrated that glycosylation significantly decreased the distribution of radiolabeled GLP-1 into the liver and increased the concentration of radiolabeled GLP-1 in plasma. These results suggested that glycosylation is a useful strategy for decreasing the distribution into the liver of bioactive peptides as desirable pharmaceuticals. (author)

  19. Identification of Staphylococcus aureus infection by aptamers directly radiolabeled with technetium-99m

    International Nuclear Information System (INIS)

    Santos, Sara Roberta dos; Rodrigues Corrêa, Cristiane; Branco de Barros, André Luís; Serakides, Rogéria; Fernandes, Simone Odília

    2015-01-01

    Introduction: Aptamers are oligonucleotides that have high affinity and specificity for their molecular targets which are emerging as a new class of molecules for radiopharmaceuticals development. In this study, aptamers selected to Staphylococcus aureus were evaluated for bacterial infection identification. Methods: Anti S. aureus aptamers were labeled with 99m Tc by the direct method. The radiolabel yield and complex stability were assessed by thin-layer chromatography (TLC). Three groups of Swiss mice containing 6 animals each were used. The first group was infected intramuscularly in the right thigh with S. aureus. The second group was infected in the same way with C. albicans and the third group was injected with zymosan to induce aseptic inflammation. After 24 h, radiolabeled aptamers (22.2 MBq) were injected by the tail vein. The mice were euthanized 4 h post injection and tissue sample activities measured in a gamma counter. Results: The 99m Tc labeled aptamers were stable in saline, plasma and cystein excess. Radiolabeled aptamers showed increased uptake in the kidneys for all groups indicating a main renal excretion, which is consistent with the hydrophilic nature and small size of aptamers. The radiopharmaceutical showed rapid blood clearance indicated by a reduced dose (% ID/g) in the blood. The biodistribution showed that aptamers were able to identify the infection foci caused by S. aureus displaying a target/non-target ratio of 4.0 ± 0.5. This ratio for mice infected with C. albicans was 2.0 ± 0.4 while for mice with aseptic inflammation was 1.2 ± 0.2. Histology confirmed the presence of infection in groups 1 and 2, and inflammation in group 3. Conclusions: The biodistibution study demonstrated a statistically higher uptake in the S. aureus foci relative to inflammation and C. albicans infected areas. These results highlight the potential of aptamers labeled directly with 99m Tc for bacterial infection diagnosis by scintigraphy

  20. Liquid phase radioimmunoassay system for determination of progesterone in human serum using different radiolabeled tracers

    International Nuclear Information System (INIS)

    Mehany, N.L.; El-Kolaly, M.T.; Sallam, Kh.M.; EI-Hashash, M.A.

    2007-01-01

    The preparation and development of primary reagents of progesterone radioimmunoassay (R1A) technique with low cost is considered to be the main objective of the present study . The preparation of 125 l-progesterone radiotracers was carried out using chloramine-T, iodogen and lactoperoxidase oxidation methods and they were purified using high perfomance liquid chromatography (HPLC). Tyramine hydrochloride was conjugated with activated progesterone 11α-hemisuccinate and then iodinated using Na 125 I.The tracers obtained were investigated in terms of radiochemical purity, radiochemical yield and immunoreactivity. The production of polyclonal antibodies was undertaken by immunizing six New-Zealand rabbits subcutaneously through primary injection and four booster doses.The preparation of progesterone standards were carried out by preparing stock standard solution of progesterone in ethanol. After evaporation of ethanol, the steroid assay buffer was used as a standard matrix to prepare the working standards required. Optimization and validation of the assay were carried out. The results obtained provide a highly sensitive, specific and accurate RIA system of progesterone based on liquid phase separation. In conclusion, this assay could be used in evaluating corpus luteum insufficiency among women in child bearing period

  1. Preclinical evaluation of neurotensin(8-13) analog radiolabeled with 99mTc: in vitro and in vivo characterization

    International Nuclear Information System (INIS)

    Teodoro, Rodrigo

    2010-01-01

    The radiolabeling of receptor specific biomolecules with 99m Tc using bifunctional chelator agents represents a growing field in Nuclear Medicine, specially, regarding regulatory peptides, such as Neurotensin, which are important in several essential physiological functions, particularly in tumor growth. The aim of the study was the comparative radiolabeling evaluation of the double-stabilized NT(8-13) analog with 99m Tc, via the bifunctional chelating agents 6- hydrazinonicotinamide (HYNIC) and S-acetyl-mercaptoacetyltriglycine (MAG3) in MDA-MB-231 breast cancer cell line. High radiochemical yields (> 97%) and stability toward transchelant agents was observed for both radiolabeled analogs. Also, comparable in vitro behaviour regarding the percentage of plasma protein binding (nearby 22%), metabolic stability, receptor binding affinity (nM range), and internalization/externalization rates were obtained. The greater lipophilicity found for the analog radiolabeled via MAG 3 , reflected in the major differences in biodistribution studies. The in vivo metabolic stability studies suggested that the degradation observed in the later time point (90 min) for the conjugate radiolabeled via HYNIC, leads not only to lower tumor uptake accumulation (0,44±0,02% ID/g), but also to lower tumor-to-non-tumor ratios ( 3 had been confirmed in the present study, a structural re-design aiming the reduction of the high gastrointestinal uptake must be done in order to guarantee the potential applicability of MAG 3 -radio complex. (author)

  2. 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

  3. 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

  4. Radiolabelled parasite antigens as tools for diagnosis and identification of protective antigens

    International Nuclear Information System (INIS)

    Parkhouse, R.M.E.; Cabrera, Z.

    1986-01-01

    Radiolabelling specific compartments and molecules of parasites provides a valuable tool for establishing parasite antigen-host response systems with utility and/or importance in protection, diagnosis and pathology. The combined immunological, biochemical and molecular biological expertise currently available forms a sufficient basis for a relatively logical and effective programme directed towards the ultimate eradication of tropical diseases. The organization of carefully selected and clinically well characterized sera and patients, representing the range of commonly occurring parasitic infections, would be of great practical value in the pursuance of this goal. (author)

  5. 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

  6. Whole-body effective half-lives for radiolabeled antibodies and related issues

    International Nuclear Information System (INIS)

    Kaurin, D.G.L.; Carsten, A.L.; Baum, J.W.; Barber, D.E.

    1996-08-01

    Radiolabeled antibodies (RABs) are being developed and used in medical imaging and therapy in rapidly increasing numbers. Data on the whole body half effective half-lives were calculated from external dose rates obtained from attending physicians and radiation safety officers at participating institutions. Calculations were made using exponential regression analysis of data from patients receiving single and multiple administrations. Theses data were analyzed on the basis of age, sex, isotope label, radiation energy, antibody type, disease treated, administration method, and number of administrations

  7. 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.

  8. Alternate radiolabeled markers for detecting metabolic activity of Mycobacterium leprae residing in murine macrophages

    Energy Technology Data Exchange (ETDEWEB)

    Prasad, H.K.; Hastings, R.C.

    1985-05-01

    This study demonstrated the utility of using 4% NaOH as a murine macrophage cell-solubilizing agent to discriminate between host macrophage metabolism and that of intracellular Mycobacterium leprae. A 4% concentration of NaOH had no deleterious effect on labeled mycobacteria. Thereby, alternate radiolabeled indicators of the metabolic activity of intracellular M. leprae could be experimented with. Significant incorporation of /sup 14/C-amino acid mixture, (/sup 14/C)leucine, (/sup 14/C)uridine, and carrier-free /sup 32/P was observed in cultures containing freshly extracted (''live'') strains of M. leprae as compared with control cultures containing autoclaved bacilli.

  9. Alternate radiolabeled markers for detecting metabolic activity of Mycobacterium leprae residing in murine macrophages

    International Nuclear Information System (INIS)

    Prasad, H.K.; Hastings, R.C.

    1985-01-01

    This study demonstrated the utility of using 4% NaOH as a murine macrophage cell-solubilizing agent to discriminate between host macrophage metabolism and that of intracellular Mycobacterium leprae. A 4% concentration of NaOH had no deleterious effect on labeled mycobacteria. Thereby, alternate radiolabeled indicators of the metabolic activity of intracellular M. leprae could be experimented with. Significant incorporation of 14 C-amino acid mixture, [ 14 C]leucine, [ 14 C]uridine, and carrier-free 32 P was observed in cultures containing freshly extracted (''live'') strains of M. leprae as compared with control cultures containing autoclaved bacilli

  10. Parameters optimization defined by statistical analysis for cysteine-dextran radiolabeling with technetium tricarbonyl core.

    Science.gov (United States)

    Núñez, Eutimio Gustavo Fernández; Faintuch, Bluma Linkowski; Teodoro, Rodrigo; Wiecek, Danielle Pereira; da Silva, Natanael Gomes; Papadopoulos, Minas; Pelecanou, Maria; Pirmettis, Ioannis; de Oliveira Filho, Renato Santos; Duatti, Adriano; Pasqualini, Roberto

    2011-04-01

    The objective of this study was the development of a statistical approach for radiolabeling optimization of cysteine-dextran conjugates with Tc-99m tricarbonyl core. This strategy has been applied to the labeling of 2-propylene-S-cysteine-dextran in the attempt to prepare a new class of tracers for sentinel lymph node detection, and can be extended to other radiopharmaceuticals for different targets. The statistical routine was based on three-level factorial design. Best labeling conditions were achieved. The specific activity reached was 5 MBq/μg. Crown Copyright © 2011. Published by Elsevier Ltd. All rights reserved.

  11. Parameters optimization defined by statistical analysis for cysteine-dextran radiolabeling with technetium tricarbonyl core

    Energy Technology Data Exchange (ETDEWEB)

    Fernandez Nunez, Eutimio Gustavo, E-mail: eutimiocu@yahoo.co [Radiopharmacy Center, Institute of Energetic and Nuclear Research, Sao Paulo, SP 05508-000 (Brazil); Linkowski Faintuch, Bluma; Teodoro, Rodrigo; Pereira Wiecek, Danielle; Gomes da Silva, Natanael [Radiopharmacy Center, Institute of Energetic and Nuclear Research, Sao Paulo, SP 05508-000 (Brazil); Papadopoulos, Minas [Institute of Radioisotopes, Radiodiagnostic Products, National Center for Scientific Research ' Demokritos' , Athens (Greece); Pelecanou, Maria [Institute of Biology, National Center for Scientific Research ' Demokritos' , Athens (Greece); Pirmettis, Ioannis [Institute of Radioisotopes, Radiodiagnostic Products, National Center for Scientific Research ' Demokritos' , Athens (Greece); Santos Oliveira Filho, Renato de [Faculty of Medicine, Federal University of Sao Paulo, SP (Brazil); Duatti, Adriano [Department of Radiological Sciences, University of Ferrara, Ferrara (Italy); Pasqualini, Roberto [CIS Bio International, Gif sur Yvette (France)

    2011-04-15

    The objective of this study was the development of a statistical approach for radiolabeling optimization of cysteine-dextran conjugates with Tc-99m tricarbonyl core. This strategy has been applied to the labeling of 2-propylene-S-cysteine-dextran in the attempt to prepare a new class of tracers for sentinel lymph node detection, and can be extended to other radiopharmaceuticals for different targets. The statistical routine was based on three-level factorial design. Best labeling conditions were achieved. The specific activity reached was 5 MBq/{mu}g.

  12. Radiolabeled Peptide Scaffolds for PET/SPECT - Optical in Vivo Imaging of Carbohydrate-Lectin Interactions

    Energy Technology Data Exchange (ETDEWEB)

    Deutscher, Susan

    2014-09-30

    The objective of this research is to develop phage display-selected peptides into radio- and fluoresecently- labeled scaffolds for the multimodal imaging of carbohydrate-lectin interactions. While numerous protein and receptor systems are being explored for the development of targeted imaging agents, the targeting and analysis of carbohydrate-lectin complexes in vivo remains relatively unexplored. Antibodies, nanoparticles, and peptides are being developed that target carbohydrate-lectin complexes in living systems. However, antibodies and nanoparticles often suffer from slow clearance and toxicity problems. Peptides are attractive alternative vehicles for the specific delivery of radionuclides or fluorophores to sites of interest in vivo, although, because of their size, uptake and retention may be less than antibodies. We have selected high affinity peptides that bind a specific carbohydrate-lectin complex involved in cell-cell adhesion and cross-linking using bacteriophage (phage) display technologies (1,2). These peptides have allowed us to probe the role of these antigens in cell adhesion. Fluorescent versions of the peptides have been developed for optical imaging and radiolabeled versions have been used in single photon emission computed tomography (SPECT) and positron emission tomography (PET) in vivo imaging (3-6). A benefit in employing the radiolabeled peptides in SPECT and PET is that these imaging modalities are widely used in living systems and offer deep tissue sensitivity. Radiolabeled peptides, however, often exhibit poor stability and high kidney uptake in vivo. Conversely, optical imaging is sensitive and offers good spatial resolution, but is not useful for deep tissue penetration and is semi-quantitative. Thus, multimodality imaging that relies on the strengths of both radio- and optical- imaging is a current focus for development of new in vivo imaging agents. We propose a novel means to improve the efficacy of radiolabeled and fluorescently

  13. Computer-assisted high-pressure liquid chromatography of radio-labelled phenylthiohydantoin amino acids

    International Nuclear Information System (INIS)

    Bhown, A.S.; Mole, J.E.; Hollaway, W.L.; Bennet, J.C.

    1978-01-01

    A computer-controlled high-pressure liquid chromatographic (HPLC) system is described to identify in vitro phenyl [ 35 S]isothiocyanate-labelled phenylthiohydantoin (PTH) amino acids from a solid-phase sequencer. Each radio-labelled amino acid from the sequencer is added to a PTH amino acid standard and the mixture separated by HPLC using a computer, programmed to detect a slope change in the absorbance. Individual fractions corresponding to the PTH amino acids are collected and counted. The sensitivity of the system is demonstrated on 700 pmoles of lysozyme. (Auth.)

  14. Radiolabeled phosphonium salts as mitocondrial voltage sensors for positron emission tomography myocardial imaging agents

    Energy Technology Data Exchange (ETDEWEB)

    Kim, Dong Yon; Min, Jung Joon [Dept. of Nuclear Medicine,Chonnam National University Medical School and Hwasun Hospital, Gwangju (Korea, Republic of)

    2016-09-15

    Despite substantial advances in the diagnosis of cardiovascular disease, {sup 18}F-labeled positron emission tomography (PET) radiopharmaceuticals remain necessary to diagnose heart disease because clinical use of current PET tracers is limited by their short half-life. Lipophilic cations such as phosphonium salts penetrate the mitochondrial membranes and accumulate in mitochondria of cardiomyocytes in response to negative inner-transmembrane potentials. Radiolabeled tetraphenyl phosphonium cation derivatives have been developed as myocardial imaging agents for PET. In this review, a general overview of these radiotracers, including their radiosynthesis, in vivo characterization, and evaluation is provided and clinical perspectives are discussed.

  15. Whole-body effective half-lives for radiolabeled antibodies and related issues

    Energy Technology Data Exchange (ETDEWEB)

    Kaurin, D.G.L.; Carsten, A.L.; Baum, J.W.; Barber, D.E.

    1996-08-01

    Radiolabeled antibodies (RABs) are being developed and used in medical imaging and therapy in rapidly increasing numbers. Data on the whole body half effective half-lives were calculated from external dose rates obtained from attending physicians and radiation safety officers at participating institutions. Calculations were made using exponential regression analysis of data from patients receiving single and multiple administrations. Theses data were analyzed on the basis of age, sex, isotope label, radiation energy, antibody type, disease treated, administration method, and number of administrations.

  16. Scintigraphic imaging of Staphylococcus aureus infection using 99mTc radiolabeled aptamers.

    Science.gov (United States)

    Santos, Sara Roberta Dos; de Sousa Lacerda, Camila Maria; Ferreira, Iêda Mendes; de Barros, André Luís Branco; Fernandes, Simone Odília; Cardoso, Valbert Nascimento; de Andrade, Antero Silva Ribeiro

    2017-10-01

    Staphylococcus aureus is a specie of great medical importance associated with many infections as bacteremia and infective endocarditis as well as osteoarticular, skin and soft tissue, pleuropulmonary, and device related infections. Early identification of infectious foci is crucial for successful treatment. Scintigraphy could contribute to this purpose since specific radiotracers were available. Aptamers due to their high specificity have great potential for radiopharmaceuticals development. In the present study scintigraphic images of S. aureus infectious foci were obtained using specific S. aureus aptamers radiolabeled with 99m Tc. Copyright © 2017 Elsevier Ltd. All rights reserved.

  17. 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

  18. Radiolabeling of Ceftriaxone with 99mTc as a Targeting Radiopharmaceutical for Staphylococcus Aureus Detection in Mouse Model

    International Nuclear Information System (INIS)

    Fazli, A.; Saluti, M.; Ahmadi, Gh.; Mirshojaei, F.; Mazidi, M.; Heydari, Z.

    2012-01-01

    Bacterial infection is one of the major causes of morbidity and mortality especially in developing countries. Nuclear medicine has an important role in helping the diagnosis of deep-seated infections by developing more specific radiopharmaceuticals. The aim of this study was to evaluate 99mTc-labeling ceftriaxone as a new radiopharmaceutical for Staphylococcus aureus infection imaging in nuclear medicine. Radiolabeling of ceftriaxone was carried out by adding 370 MBq of 99mTc to 10 mg of ceftriaxone in the presence of 50 μg of SnCl 2 .2H 2 O at pH=5. The radiochemical purity and stability tests at room temperature and human blood serum were evaluated with ITLC. Intramuscular infection was induced by injection of Staphylococcus aureus into the left thigh muscle of the mice. The biodistribution of 99mTc-ceftriaxone was studied in normal and infected mice at various times post-injection. Radiochemical purity of the product was 94.5±5.4% with a good stability at room temperature and human serum, 80.6% and 71.2% after 24 h, respectively. The biodistribution studies showed the localization of 99mTc-ceftriaxone at the site of infection with high sensitivity without any significant accumulation in vital organs. Due to the ease of 99mTc-ceftriaxone conjugation method, high labeling efficiency, and high uptake in the infected muscle, it may provide a promising candidate as a targeting radiopharmaceutical for imaging infectious foci due to Staphylococcus aureus in nuclear medicine.

  19. Development of a novel bombesin analog radiolabeled with Lutetium-177: in vivo evaluation of the biological properties in Balb-C mice

    International Nuclear Information System (INIS)

    Pujatti, Priscilla Brunelli; Barrio, Ofelia; Santos, Josefina da Silva; Mengatti, Jair; Araujo, Elaine Bortoleti de

    2008-01-01

    Bombesin (BBN), a 14-aminoacid amphibian peptide homologue of mammalian gastrin-releasing peptide (GRP), has demonstrated the ability to bind with high affinity and specificity to GRP receptor, which are overexpressed on a variety of human cancers. A large number of BBN analogs were synthesized for this purpose and have shown to reduce tumor growth in mice. However, most of the studied analogs exhibit high abdominal accumulation, specially in pancreas. This abdominal accumulation may represent a problem in clinical use of radiolabeled bombesin analogs probably due to serious side effects to patients. In this study we describe the results of radiolabeling with lutetium-177 ( 177 Lu) and in vivo biodistribution and pharmacokinetics studies in normal Balb-C mice of a novel bombesin analog (BBNp4) - DOTA-X-BBN(6-14), where X is a spacer of four aminoacids. This spacer was inserted between the chelator and the binding sequence in order to improve bombesin in vivo properties. BBNp4 was successfully labeled with high yield and kept stable for more than 96 hours at 4 deg C and 4 hours in human plasma. Data analysis obtained from the in vivo studies showed that the amount of BBNp4 present in plasma decreased rapidly and became almost undetectable at 60 min p.i., indicating rapid peptide excretion, which is performed mainly by renal pathway. In addition, biodistribution and single photon emission tomography showed low abdominal accumulation of 177 Lu-DOTA-X-BBN(6-14), indicating that this analog is a potential candidate for tumors target therapy. (author)

  20. Radiolabelled neoglycopeptides

    International Nuclear Information System (INIS)

    Krohn, K.A.; Vera, D.R.; Stadalnik, R.C.

    1984-01-01

    This patent provides a composition comprising a galactosyl or glucosyl substituted serum albumin, having from about 5 to 40 galactosyl or glucosyl groups, combined with a reductant for pertechnetate sufficient to provide Tc-99m in an amount of from about 1 to 100 mCi/mg albumin

  1. Radiolabeled leukocytes

    International Nuclear Information System (INIS)

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

    1986-01-01

    Leukocytes are a heterogeneous group of nucleated cells that follow similar patterns of differentiation in the bone marrow. Although the various leukocyte cell types perform somewhat different functions, they act as a group to protect the host from hazards of the internal and external environment, such as infection and neoplasia, and they assist in the repair of damaged tissue. Leukocytes spend a small fraction of their life in the peripheral blood, using it only for transportation to sites where they are needed to perform their defensive functions. In adults, the mature types of leukocytes are neutrophils (59 percent of the leukocyte population), lymphocytes (34 percent), monocytes (four percent), eosinophils (three percent), and basophils (0.5 percent). Neutrophils, eosinophils, and basophils all contain nuclei with finitely granular, evenly distributed chromatin and are collectively called granulocytes. In addition to the main categories of leukocytes listed above, there are subsets of many of these classes of cells; for example, natural killer cells are a subset of lymphocytes

  2. Peptide synthesis, characterization and 68Ga-radiolabeling of NOTA-conjugated ubiquicidin fragments for prospective infection imaging with PET/CT

    International Nuclear Information System (INIS)

    Ebenhan, Thomas; Chadwick, Nicholas; Sathekge, Mike M.; Govender, Patrick; Govender, Thavendran; Kruger, Hendrik G.; Marjanovic-Painter, Biljana; Zeevaart, Jan Rijn

    2014-01-01

    Introduction: Human antimicrobial peptides are of interest for the development of positron emission tomography (PET) tracers as they exhibit desirable characteristics that make them good candidates for targeting vectors. Due to their natural role in the innate immune system they selectively bind to pathogenic bacteria and yeast, whilst remaining minimally immunogenic and cytotoxic to humans. Research into ubiquicidin (UBI)-based tracers has focused on 99m Tc as a radionuclide, however, the use of bi-functional chelators such as 1,4,7-triazacyclononane-1,4,7-triacetic acid (NOTA), in combination with 68 Ga as a radionuclide, allows for a simple radiolabeling procedure which is preferable in a clinical setting using PET/CT. Methods: The peptides fragments UBI29-41, UBI30-41 were synthesized by standard microwave Fmoc/tert-butyl (tBu)-solid phase synthetic protocols. Characterizations were performed using analytical HPLC and LC/MS. Both NOTA-conjugated peptides were exposed to nat Ga 3+ ; their complexed form was quantified by direct LC/MS injection. This complexation was utilized to testify bacterial and mammalian cell binding potential of fluorophore-linked NOTA-UBI29-41/30-41. 68 Ga labeled NOTA-UBI fragments were also tested for competitive interaction to Staphylococcus aureus to proof the binding target. 68 Ga was eluted from SnO 2 - and TiO 2 -based 68 Ge/ 68 Ga generators using fractionated elution and anion exchanged-based post-procession. NOTA-peptide radiolabeling was carried out including optimization of buffer molarity, NOTA-peptide concentration(s), incubation temperature and –duration as well as considering various SPE purification cartridges. Results: Pure UBI29-41, UBI30-41 and NOTA-UBI30-41 were successfully characterized. Both, NOTA-UBI fragments exhibited complexation rates to nat Ga 3+ ≥ 99%. The percentage binding was significantly higher to Staphylococcus aureus bacilli over Mt4 human leucocytes (P > 0.05) for NOTA-UBI29-41[Lys(Abz)] < NOTA

  3. Positron-emitting resin microspheres as surrogates of 90Y SIR-Spheres: a radiolabeling and stability study

    International Nuclear Information System (INIS)

    Avila-Rodriguez, Miguel A.; Selwyn, Reed G.; Hampel, Joseph A.; Thomadsen, Bruce R.; DeJesus, Onofre T.; Converse, Alexander K.; Nickles, Robert J.

    2007-01-01

    Commercially available resin microspheres and SIR-Spheres were labeled with metallic positron emitters and evaluated as positron emission tomography (PET) imaging surrogates of 90 Y SIR-Spheres. Radiolabeling was performed using a batch method, and in vitro stability over 24 h was evaluated in saline at physiological pH at 37 o C. The activity per microsphere distribution, as evaluated by autoradiography, showed the activity per microsphere to be proportional to the square radius of the spheres, suggesting surface binding. The in vivo stability of radiolabeling was evaluated in rats by micro-PET imaging after the intravenous injection of labeled microspheres. The different resin microspheres and radionuclides evaluated in this study all showed good radiolabeling efficiency and in vitro stability. However, only resins labeled with 86 Y and 89 Zr proved to have the in vivo stability required for clinical applications

  4. Brief study about the distribution of recombinant human Epidermic Growth Factor (rh-EGF)

    International Nuclear Information System (INIS)

    Rodriguez Garcia, J.C.; De Dios D Espaux, R.; Bello Garciga, J.L.

    1997-01-01

    This report describes results of the study about biodistribution of I-125 recombinant human Epidermic Growth Factor (rhEGF). The radiolabelled product was administrated to Sprague Dawley rats in three different ways: intramuscular, subcutaneous and epidermic; the highest concentration of EGF in blood was found 4 hours after rhEGF administration, with a greater distribution in the plasma with regard to cellular pellet. The slowest plasma clearance corresponded to the intramuscular administration. The highest concentration of radiolabelled rhEGF was found in liver, kidney and intestine. It was found that radiolabelled EGF is excreted mainly throughout urine and faeces although other excretion pathways could exist

  5. 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

  6. The use of radiolabelled milk proteins to study thermally-induced interactions in milk systems

    International Nuclear Information System (INIS)

    Noh, B.

    1988-01-01

    Heat induced complexes between milk proteins are of considerable importance in determining the heat stability and rennin clottability of milk products. Thiol-disulfide interchange reactions have been suggested as the principal reaction mechanism for complex formation. Studies to data have not adequately established the mechanism and stoichiometry of complex formation in situ in total milk system. Tracer amounts of 14 C-β-lactoglobulin and α-lactalbumin were heated under various conditions. After clotting with rennet, radioactivity retained in the curd was counted to estimate extent of interaction of β-lactoglobulin with casein. 14 C- and 3 H-Methyl labelled proteins were used for the preparation of radiolabelled artificial casein micelles. These micelles with radiolabelled whey proteins were heated and heat-induced complexes were separated on Sephacryl S-300 eluting with 6 M guanidine hydrochloride to break all non-covalent bonds. Further separation of the protein complexes was obtained using CPG-10 or Sephacryl S-1000. The ratios of 3 H to 14 C labelled proteins in the protein complexes suggested that the stoichiometries of k-, α s2 -casein, β-lactoglobulin and α-lactalbumin in the heat-induced complexes varied as a function of the heat treatment

  7. Detection of early atherosclerosis with radiolabeled monocyte chemoattractant protein-1 in prediabeteic Zucker rats

    Energy Technology Data Exchange (ETDEWEB)

    Blankenberg, F.G. [Div. of Pediatric Radiology, Stanford, CA (United States); Wen, P.; Dai, M.; Zhu, D.; Panchal, S.N.; Valantine, H.A. [Division of Cardiovascular Medicine, Department of Medicine, Stanford, California (United States); Tait, J.F. [Dept. of Laboratory Medicine, Univ. of Washington, Seattle (United States); Post, A.M.; Strauss, H.W. [Div. of Nuclear Medicine, Stanford Univ., CA (United States)

    2001-12-01

    Background: Migration of monocytes into the arterial wall is an early finding of atherosclerosis. Monocytes are attracted to sites of vascular endothelial cell injury, the initiating event in the development of atheromatous disease, by a chemokine known as monocyte chemoattractant protein-1 (MCP-1). Injured vascular endothelial and smooth muscle cells selectively secrete MCP-1. Objective: This study was performed to determine if radiolabeled MCP-1 would co-localize at sites of monocyte/macrophage concentration in an experimental model of transplant-induced vasculopathy in diabetic animals. Materials and methods: Hearts from 3-month-old male Zucker rats, heterozygote (Lean) or homozygote (Fat) for the diabetes-associated gene fa, were transplanted into the abdomens of genetically matched recipients. Lean and Fat animals were then fed normal or high-fat diets for 90 days. Results: At 90 days significant increases (P < 0.013) of MCP-1 graft uptake were seen at imaging and confirmed on scintillation gamma well counting studies in Lean (n = 5) and Fat (n = 12) animals, regardless of diet, 400 % and 40 %, above control values, respectively. MCP-1 uptake of native and grafted hearts correlated with increased numbers of perivascular macrophages (P < 0.02), as seen by immunostaining with an antibody specific for macrophages (ED 2). Conclusion: Radiolabeled MCP-1 can detect abnormally increased numbers of perivascular mononuclear cells in native and grafted hearts in prediabetic rats. MCP-1 may be useful in the screening of diabetic children for early atherosclerotic disease. (orig.)

  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. Scintigraphic detection of peptic lesions with the method of radiolabelled sucralfate

    International Nuclear Information System (INIS)

    Naumovski, J.; Kovkarova, E.; Simova, N.; Janevik-Ivanovska, E.; Georgievska- Kuzmanovska, S.

    2003-01-01

    Background. Sucralfate is an antiulcer agent that after peroral application strongly adheres to mucosal defects and in that way provides a protective barrier to further damage from acid and pepsin. If radiolabelled with a gamma isotope, it could be detected under a gamma camera pointing lesions to which it adhered. With the aim to confirm a suitable noninvasive method for investigation of caustic lesions of the upper gastrointestinal tract we evaluated in a preliminary study the validity of the radiolabelled Sucralfate scintigraphy in detection of peptic disease. Patients and methods. With that purpose, 35 patients after an endoscopic examination underwent scintigraphy with Tc-99m-DTPA sucralfate. Patients were divided in two groups: a group of 20 patients with endoscopic confirmed peptic disease and a control group of 15 persons who had not any disease of the upper gastrointestinal tract. Results. Using the test for clinical evaluation of a new method, the scan showed sensitivity of 75 %, specificity of 100 % and accuracy of 85.7 %. Conclusions. Scintigraphy with Tc-99m-DTPA Sucralfate promoting it as an additional method, complementary to routine investigations in detecting mucosal lesions. (author)

  11. Preliminary investigations on the preparation of gold nanoparticles intrinsically radiolabeled with 199Au

    International Nuclear Information System (INIS)

    Vimalnath, K.V.; Chakraborty, Sudipta; Dash, Ashutosh

    2016-01-01

    Radiolabeled nanoparticles are of great interest in the current perspective of the nuclear medicine. Water dispersible materials with nanoscale dimensions are finding role in biomedical application owing to their size. These particles can access otherwise unreachable regions in tumor mainly due to Enhanced Permeability and Retention (EPR) effect. Nanoparticles of gold (AuNPs) can bind to a wide range of biologically active molecules with functional groups that have high affinity for the gold surface. Sulfur containing compounds (e.g. thiols, disulfides), organic phosphates, amines, PEG, etc. are some of the well known surface modifiers. Functional thiolates, oligonucleotides, peptides and PEGs are introduced upon subsequent bimolecular substitution of a ligand by a functional thiol easily attached to AuNPs. Owing to its favourable decay characteristics 199 Au (T 1/2 = 3.15 d, E âmax = 474 keV, Eg 158.4 keV (36.9 %) and 208.2 keV (8.4 %)) is an attractive radionuclide for theragnostic applications. In the present work, we have carried out preliminary radiochemical investigations on the preparation of gold nanoparticles intrinsically radiolabeled with 199 Au for its potential utility as a theragnostic agent targeted delivery to the tumors

  12. CT-guided radiolabelled aerosol studies for assessing pulmonary impairment in children with bronchiectasis

    International Nuclear Information System (INIS)

    Pifferi, M.; Baldini, M.; Caramella, D.; Bartolozzi, C.; Di Mauro, M.; Cangiotti, A.M.

    2000-01-01

    Objective. To determine whether CT-guided mucociliary clearance studies allow differentiation between bronchiectasis associated with primary ciliary dyskinesia (PCD) and those unrelated to congenital or genetically transmitted defects. Materials and methods. Fifteen children aged 4-18 years with a CT diagnosis of bronchiectasis were included in the study. Six had PCD, while in nine cases no congenital disorder was demonstrated. Results. CT showed bronchiectasis in 26 (29 %) of 90 lung regions. Radiolabelled aerosol studies were conducted globally for each lung and on the regions affected by bronchiectasis. Global half-time of activity (t 1/2 ) values of patients with PCD were significantly higher (P 1/2 values. Patients with bronchiectasis unrelated to congenital disorders showed significantly higher regional t 1/2 values in the affected regions with respect to the corresponding global pulmonary t 1/2 (P < 0.06). Conclusions. The combination of morphological CT information with functional data concerning the clearance of radiolabelled aerosol adds to our understanding of pulmonary impairment in children with bronchiectasis. In particular, regional studies allow the recognition of different mucociliary clearance patterns in bronchiectasis associated with PCD and those unrelated to congenital or genetically transmitted defects. (orig.)

  13. 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)

  14. Detection of early atherosclerosis with radiolabeled monocyte chemoattractant protein-1 in prediabeteic Zucker rats

    International Nuclear Information System (INIS)

    Blankenberg, F.G.; Wen, P.; Dai, M.; Zhu, D.; Panchal, S.N.; Valantine, H.A.; Tait, J.F.; Post, A.M.; Strauss, H.W.

    2001-01-01

    Background: Migration of monocytes into the arterial wall is an early finding of atherosclerosis. Monocytes are attracted to sites of vascular endothelial cell injury, the initiating event in the development of atheromatous disease, by a chemokine known as monocyte chemoattractant protein-1 (MCP-1). Injured vascular endothelial and smooth muscle cells selectively secrete MCP-1. Objective: This study was performed to determine if radiolabeled MCP-1 would co-localize at sites of monocyte/macrophage concentration in an experimental model of transplant-induced vasculopathy in diabetic animals. Materials and methods: Hearts from 3-month-old male Zucker rats, heterozygote (Lean) or homozygote (Fat) for the diabetes-associated gene fa, were transplanted into the abdomens of genetically matched recipients. Lean and Fat animals were then fed normal or high-fat diets for 90 days. Results: At 90 days significant increases (P < 0.013) of MCP-1 graft uptake were seen at imaging and confirmed on scintillation gamma well counting studies in Lean (n = 5) and Fat (n = 12) animals, regardless of diet, 400 % and 40 %, above control values, respectively. MCP-1 uptake of native and grafted hearts correlated with increased numbers of perivascular macrophages (P < 0.02), as seen by immunostaining with an antibody specific for macrophages (ED 2). Conclusion: Radiolabeled MCP-1 can detect abnormally increased numbers of perivascular mononuclear cells in native and grafted hearts in prediabetic rats. MCP-1 may be useful in the screening of diabetic children for early atherosclerotic disease. (orig.)

  15. A study of radiolabelling parameters of 1/5 fractionated cardiolite

    International Nuclear Information System (INIS)

    Forster, M.; Snowdon, G.M.

    1997-01-01

    Full text: Fractionation of Cardiolite (Dupont Pharma) has in recent times become increasingly popular in order to minimise costs in our funds-strapped public health system. We investigated the following parameters which are known to potentially affect 1/5 Cardiolite radiolabelling efficiency: 1. Radioactivity-4 to 12 GBq per vial. 2. Total volumes-2.5 and 6.5 mL per vial. 3. Boiling times-2 to 10 minutes. 4. Extra stannous chloride concentration-16 and 32 mg. 5. Quality control procedure-ITLC-SG v. Sep Pak Lite column chromatography. The addition of extra stannous chloride was essential to achieve radiochemical purity >90%. Increasing the total vial volume had a deleterious effect on radiochemical purity. A radiochemical purity >90% was achieved after four minutes boiling of 1/5 fractionated Cardiolite radiolabelled with an activity of up to 10 GBq [ 99m Tc] sodium pertechnetate provided 32 μg 99m Tc stannous chloride was added to the Cardiolite vial prior to the addition of sodium pertechnetate. The ITLC-SG quality control method gave a constantly higher radiochemical purity estimation (∼ 3%) than the Sep Pak Lite method. This was assumed to be due to a radiochemical impurity not detected by ITLC-SG but confirmed on HPLC via personal communication with the radiochemists from St George Hospital, Sydney

  16. 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

  17. A novel method for synthesis of {sup 56}Co-radiolabelled silica nanoparticles

    Energy Technology Data Exchange (ETDEWEB)

    Cydzik, I. [Institute for Health and Consumer Protection, European Commission, Joint Research Centre (Italy); Bilewicz, A. [Institute of Nuclear Chemistry and Technology (Poland); Abbas, K. [Institute for Transuranium Elements (Ispra Site), European Commission, Joint Research Centre (Italy); Simonelli, F.; Bulgheroni, A.; Holzwarth, U., E-mail: uwe.holzwarth@jrc.ec.europa.eu; Gibson, N. [Institute for Health and Consumer Protection, European Commission, Joint Research Centre (Italy)

    2012-10-15

    A method for synthesis of radiolabelled amorphous silica nanoparticles is presented. The method is based on the well-known Stoeber process with the exception that {sup 56}Co radiotracer is introduced into one of the precursor materials prior to the initiation of the nanoparticle synthesis. The {sup 56}Co was prepared by proton irradiation of an iron foil, followed by dissolution in hydrochloric acid and {sup 56}Co/Fe radiochemical separation. In order to determine the residual Fe in the {sup 56}Co radiotracer solution, ICP-MS measurements were performed. Nanoparticles in the size range 20-100 nm were synthesised and characterised by gamma spectrometry, ICP-MS, XRD, DLS, and Zeta potential measurement. It was shown that the size and Zeta potential of the nanoparticles was roughly the same following synthesis with or without added {sup 56}Co, and in both cases, the structure was that of amorphous silica. It was found that 99.5 % of the {sup 56}Co was bound into the nanoparticles during synthesis, and centrifugation experiments confirmed that the radiolabels were stably incorporated into the silica matrix.

  18. Radiolabeling and physicochemical characterization of boron nitride nanotubes functionalized with glycol chitosan polymer

    Energy Technology Data Exchange (ETDEWEB)

    Soares, Daniel Cristian Ferreira; Ferreira, Tiago Hilario; Ferreira, Carolina de Aguiar; Sousa, Edesia Martins Barros de, E-mail: sousaem@cdtn.b [Centro de Desenvolvimento da Tecnologia Nuclear (CDTN/CNEN-MG) Belo Horizonte, MG (Brazil). Lab. de Materiais Nanoestruturados para Bioaplicacoes; Cardoso, Valbert Nascimento, E-mail: cardosov@farmacia.ufmg.b [Universidade Federal de Minas Gerais (UFMG), Belo Horizonte, MG (Brazil). Fac. de Farmacia

    2011-07-01

    In the last years, some nanostructured systems has proposed as new drugs and radioisotopes delivery systems, aiming the diagnosis and treatment of many diseases, including the cancer. Among these systems, the Boron Nitride Nanotubes (BNNTs) showed adequate characteristics to be applied in biomedical area, due to its high stability and considerable biocompatibility. However, due to its hydrophobic characteristics, these applications are limited and its behavior in vivo (guinea pigs) is unexplored yet. Seeking to overcome this problems, in the present work, we functionalized the BNNTs (noncovalent wrapped) with glycol chitosan (GC), a biocompatible and stable polymer, in order to disperse it in water. The results showed that BNNTs were well dispersed in water with mean size and polydispersity index suitable to conduct biodistribution studies in mice. The nanostructures were physicochemical and morphologically characterized by Scanning Electron Microscopy (SEM), X-ray diffraction (XRD) and Raman Spectroscopy. The results revealed that the functionalization process with glycol chitosan was obtained with successfully on BNNTs surface. Furthermore, we developed a radiolabeling protocol with {sup 99m}Tc radioisotope in functionalized BNNTs, aiming in future, to conduct image biodistribution studies in mice. The results revealed that the nanotubes were radiolabeled with radiochemical purity above of 90%, being considered suitable to scintigraphic image acquisition. (author)

  19. N-(m-[125I]iodophenyl)maleimide: an agent for high yield radiolabeling of antibodies

    International Nuclear Information System (INIS)

    Khawli, L.A.; Van den Abbeele, A.D.; Kassis, A.I.

    1992-01-01

    In an effort to radiolabel antibodies, N-(m-[ 125 I]iodophenyl)maleimide (m-[ 125 I]IPM) was prepared by the demetallation of an N-[m-tri-(n-butyl)stannylphenyl]maleimide intermediate. The unlabeled intermediate was synthesized in ≥ 75% yield using a palladium catalyzed reaction of hexabutylditin with m-bromoaniline, followed by reaction with maleic anhydride and ring annulation. All products were confirmed by NMR and elemental analysis. Labeling with 125 I was carried out in a biphasic mixture containing chloramine-T (radiochemical yield ≥ 70%). Rabbit IgG modified with the heterobifunctional crosslinking agent N-succinimidyl-3-(2-pyridyldithio)propionate (SPDP) and bovine serum albumin were conjugated with m-[ 125 I]IPM (yield: 40 and 80%, respectively). In addition, m-[ 125 I]IPM was conjugated to rabbit IgG subunits (HL) in 70% yield. The in vitro stability of the radiolabeled proteins in serum showed < 1% deiodination over 24h. (author)

  20. Integrity of 111In-radiolabeled superparamagnetic iron oxide nanoparticles in the mouse

    International Nuclear Information System (INIS)

    Wang, Haotian; Kumar, Rajiv; Nagesha, Dattatri; Duclos, Richard I.; Sridhar, Srinivas; Gatley, Samuel J.

    2015-01-01

    Introduction: Iron-oxide nanoparticles can act as contrast agents in magnetic resonance imaging (MRI), while radiolabeling the same platform with nuclear medicine isotopes allows imaging with positron emission tomography (PET) or single-photon emission computed tomography (SPECT), modalities that offer better quantification. For successful translation of these multifunctional imaging platforms to clinical use, it is imperative to evaluate the degree to which the association between radioactive label and iron oxide core remains intact in vivo. Methods: We prepared iron oxide nanoparticles stabilized by oleic acid and phospholipids which were further radiolabeled with 59 Fe, 14 C-oleic acid, and 111 In. Results: Mouse biodistributions showed 111 In preferentially localized in reticuloendothelial organs, liver, spleen and bone. However, there were greater levels of 59 Fe than 111 In in liver and spleen, but lower levels of 14 C. Conclusions: While there is some degree of dissociation between the 111 In labeled component of the nanoparticle and the iron oxide core, there is extensive dissociation of the oleic acid component

  1. Radiolabeling and physicochemical characterization of boron nitride nanotubes functionalized with glycol chitosan polymer

    International Nuclear Information System (INIS)

    Soares, Daniel Cristian Ferreira; Ferreira, Tiago Hilario; Ferreira, Carolina de Aguiar; Sousa, Edesia Martins Barros de; Cardoso, Valbert Nascimento

    2011-01-01

    In the last years, some nanostructured systems has proposed as new drugs and radioisotopes delivery systems, aiming the diagnosis and treatment of many diseases, including the cancer. Among these systems, the Boron Nitride Nanotubes (BNNTs) showed adequate characteristics to be applied in biomedical area, due to its high stability and considerable biocompatibility. However, due to its hydrophobic characteristics, these applications are limited and its behavior in vivo (guinea pigs) is unexplored yet. Seeking to overcome this problems, in the present work, we functionalized the BNNTs (noncovalent wrapped) with glycol chitosan (GC), a biocompatible and stable polymer, in order to disperse it in water. The results showed that BNNTs were well dispersed in water with mean size and polydispersity index suitable to conduct biodistribution studies in mice. The nanostructures were physicochemical and morphologically characterized by Scanning Electron Microscopy (SEM), X-ray diffraction (XRD) and Raman Spectroscopy. The results revealed that the functionalization process with glycol chitosan was obtained with successfully on BNNTs surface. Furthermore, we developed a radiolabeling protocol with 99m Tc radioisotope in functionalized BNNTs, aiming in future, to conduct image biodistribution studies in mice. The results revealed that the nanotubes were radiolabeled with radiochemical purity above of 90%, being considered suitable to scintigraphic image acquisition. (author)

  2. Evaluation of 4-[18F]fluoro-1-butyne as a radiolabeled synthon for click chemistry with azido compounds

    International Nuclear Information System (INIS)

    Kim, Dong Hyun; Choe, Yearn Seong; Kim, Byung-Tae

    2010-01-01

    Click chemistry is a useful approach for the preparation of novel radiopharmaceuticals. In this study, we evaluated 4-[ 18 F]fluoro-1-butyne as a radiolabeled synthon for click chemistry with azido compounds. Our results showed that nucleophilic substitution of 4-tosyloxy-1-butyne with K[ 18 F]F produces vinyl acetylene as well as 4-[ 18 F]fluoro-1-butyne, while the same reaction using 5-tosyloxy-1-pentyne gives exclusively 5-[ 18 F]fluoro-1-pentyne. Thus, ω-[ 18 F]fluoro-1-alkynes with chain lengths longer than four carbons may be better radiolabeled synthons for use in click chemistry.

  3. Computer simulations and the use of radiolabelled sulphur colloid to measure the efficiency of the mononuclear phagocyte system

    International Nuclear Information System (INIS)

    Saad, A.H.; Rutishauser, S.C.B.; Williams, A.R.

    1985-01-01

    Techniques are described whereby the clearance of the radiolabelled blood borne colloid can be continuously and reproducibly measured non-invasively from the same animal in vivo or from the isolated perfused intact liver in vitro. Using these techniques, the rate of removal of radiolabelled sulphur colloid by the mononuclear phagocytes in vivo and in vitro was shown to be biexponential. The pattern of clearance of colloid and the factors contributing to this were analysed with the aid of a computer program which mimicked the in vitro liver perfusion. (Auth.)

  4. 99m Tc-UBI 29-41: radiolabelled antimicrobial peptide for the diagnostic by image of infectious processes

    International Nuclear Information System (INIS)

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

    2005-01-01

    Recently the radiolabelled anti microbic peptides has intended as new radiopharmaceuticals for distinguish a bacterial infection of a sterile inflammatory process through a diagnostic image. The ubiquicidine 29-41 (UBI), it is a fragment of an anti microbic cationic peptide located in the human skin whose sequence of amino acids is Thr-Gly-Arg-Ala-Lys-Arg-Arg-Met-Gln-Tyr-Asn-Arg-Arg. The objective of this study was to develop a derived of the UBI 29-41 radiolabelled with Tc-99m in high radiochemical purity and to evaluate the feasibility of using it in the specific detection of infectious focuses. The molecular structures of the UBI as well as of other 2 cationic peptides used as control (Tat-1-Scr and Tat-2-Scr), they were calculated and optimized in their more stable configuration by molecular mechanics procedures and quantum mechanics. Once established the site for the labelled with 99m Tc, the three complexes were represented by the general formula [Tc(V)(O)(H 2 O) 2 (Lys n=1,2 -Arg n=0.1 -peptide)] 10+,11+ , with potential energy of 104.5 Kcal/mol, 95.6 Kcal/mol and 90.8 Kcal/mol for the 99m Tc-Tat-1-Scr, 99m Tc-Tat-2-Scr and 99m Tc-UBI 29-41 respectively. The three radio complexes got ready experimentally and their stability in vitro saline solution is evaluated, human serum and cysteine solutions. The experimental results correlated appropriately with the calculated data. The specificity in vitro was carried out evaluating the percentage of union of the 99m Tc-UBI 29-41 as well as of the control peptides at bacteria of S. aureus and two tumoral cellular lines (LS174T and ACHN). The In vivo specificity was determined using Balb-C mice with induction in a paw of an infectious process and in another paw of a sterile inflammatory process. Simultaneously it was administered to the mice with infection and inflammation induced 99m Tc-UBI 29-41 and 67 Ga-citrate this last an unspecific radiopharmaceutical used so much in the detection of infectious processes as

  5. Radiolabeled anti-EGFR-antibody improves local tumor control after external beam radiotherapy and offers theragnostic potential

    International Nuclear Information System (INIS)

    Koi, Lydia; Bergmann, Ralf; Brüchner, Kerstin; Pietzsch, Jens; Pietzsch, Hans-Jürgen; Krause, Mechthild

    2014-01-01

    Purpose: The effect of radioimmunotherapy (RIT) using the therapeutic radionuclide Y-90 bound to the anti-EGFR antibody cetuximab combined with external beam irradiation (EBRT) (EBRIT) on permanent local tumor control in vivo was examined. Methods: Growth delay was evaluated in three human squamous cell carcinoma models after RIT with [ 90 Y]Y-(CHX-A′′-DTPA) 4 -cetuximab (Y-90-cetuximab). The EBRT dose required to cure 50% of the tumors (TCD 50 ) for EBRT alone or EBRIT was evaluated in one RIT-responder (FaDu) and one RIT-non-responder (UT-SCC-5). EGFR expression and microenvironmental parameters were evaluated in untreated tumors, bioavailability was visualized by PET using ([ 86 Y]Y-(CHX-A′′-DTPA) 4 -cetuximab (Y-86-cetuximab) and biodistribution using Y-90-cetuximab. Results: In UT-SCC-8 and FaDu but not in UT-SCC-5 radiolabeled cetuximab led to significant tumor growth delay. TCD 50 after EBRT was significantly decreased by EGFR-targeted RIT in FaDu but not in UT-SCC-5. In contrast to EGFR expression, parameters of the tumor micromilieu and in particular the Y-90-cetuximab biodistribution or Y-86-cetuximab visualization in PET correlated with the responsiveness to RIT or EBRIT. Conclusion: EGFR-targeted EBRIT can improve permanent local tumor control compared to EBRT alone. PET imaging of bioavailability of labeled cetuximab appears to be a suitable predictor for response to EBRIT. This theragnostic approach should be further explored for clinical translation

  6. A Novel Selective Inverse Agonist of the CB2 Receptor as a Radiolabeled Tool Compound for Kinetic Binding Studies.

    Science.gov (United States)

    Martella, Andrea; Sijben, Huub; Rufer, Arne C; Grether, Uwe; Fingerle, Juergen; Ullmer, Christoph; Hartung, Thomas; IJzerman, Adriaan P; van der Stelt, Mario; Heitman, Laura H

    2017-10-01

    The endocannabinoid system, and in particular the cannabinoid type 2 receptor (CB2R), raised the interest of many medicinal chemistry programs for its therapeutic relevance in several (patho)physiologic processes. However, the physico-chemical properties of tool compounds for CB2R (e.g., the radioligand [ 3 H]CP55,940) are not optimal, despite the research efforts in developing effective drugs to target this system. At the same time, the importance of drug-target binding kinetics is growing since the kinetic binding profile of a ligand may provide important insights for the resulting in vivo efficacy. In this context we synthesized and characterized [ 3 H]RO6957022, a highly selective CB2R inverse agonist, as a radiolabeled tool compound. In equilibrium and kinetic binding experiments [ 3 H]RO6957022 showed high affinity for human CB2R with fast association ( k on ) and moderate dissociation ( k off ) kinetics. To demonstrate the robustness of [ 3 H]RO6957022 binding, affinity studies were carried out for a wide range of CB2R reference ligands, spanning the range of full, partial, and inverse agonists. Finally, we used [ 3 H]RO6957022 to study the kinetic binding profiles (i.e., k on and k off values) of selected synthetic and endogenous (i.e., 2-arachidonoylglycerol, anandamide, and noladin ether) CB2R ligands by competition association experiments. All tested ligands, and in particular the endocannabinoids, displayed distinct kinetic profiles, shedding more light on their mechanism of action and the importance of association rates in the determination of CB2R affinity. Altogether, this study shows that the use of a novel tool compound, i.e., [ 3 H]RO6957022, can support the development of novel ligands with a repertoire of kinetic binding profiles for CB2R. Copyright © 2017 by The American Society for Pharmacology and Experimental Therapeutics.

  7. Synthesis, radiolabeling and bioevaluation of a novel arylpiperazine derivative containing triazole as a 5-HT1A receptor imaging agents

    International Nuclear Information System (INIS)

    Hassanzadeh, Leila; Erfani, Mostafa; Najafi, Reza; Shafiei, Mohammad; Amini, Mohsen; Shafiee, Abbass; Ebrahimi, Seyed Esmaeil Sadat

    2013-01-01

    Introduction: It has been recognized that serotonin plays a main role in various pathological conditions such as anxiety, depression, aggressiveness, schizophrenia, suicidal behavior, panic and autism. 1-(2-Methoxyphenyl) piperazine pharmacophore, a fragment of the true 5-HT 1A antagonist WAY100635, is found in numerous selective 5-HT 1A imaging agents. In this paper, we have reported the synthesis of a novel derivative of 1-(2-methoxyphenyl) piperazine that is labeled with 99m Tc (CO) 3 via click chemistry. Methods: The bidentate alkyne, propargylglycine was reacted with phenyl piperazine triazole derivative in the presence of a catalytic amount of Cu (I) to form tridentate ligand. The ligand was radiolabeled with the precursor [ 99m Tc] [(H 2 O) 3 (CO) 3 ] + and characterized by HPLC. The bioevaluation of radio labeled ligand was carried out in rats. Results: Triazole complex was labeled by 99m Tc-tricarbonyl and its radiochemical yield was more than > 95% which was determined by HPLC. In vivo stability studies in human serum albumin show a 93% ratio of complex after a 24 h period. The calculated partition coefficient (logP) was 0.34 ± 0.02. Receptor binding assays indicated about 70% specific binding of radioligand to 5-HT 1A receptors. Biodistribution studies have shown brain hippocampus uptake of 0.40 ± 0.08 %ID/g at 30 min post injection. Conclusions: Results indicate that this 99m Tc-tricabonyl-arylpiperazine derivative has specific binding to 5-HT 1A receptors and presented suitable characters for its use as a CNS imaging agent

  8. 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.)

  9. ECT with /sup 123/I-labeled fragments of anti-CEA monoclonal antibodies in colo-rectal cancer

    International Nuclear Information System (INIS)

    Bischof-Delaloye, A.; Delaloye, B.

    1986-01-01

    The recent progress of tumor localization with labelled antibodies can be attributed to three techniques: 1) use of I-123 as a label; 2) fragmentation of antibodies; 3) tomographic recording and evaluation of patient radiation data. Under these conditions the method yields good sensitivity and specifity indexes (15/16 for primary tumors and local recurrences, 7/10 for metastasis). A strictly prospective study, however, remains mandatory in order to assess the clinical value of this method

  10. Preparation of anti-CEA and anti-goat γ-globulin sera for radioimmunologic assay of carcinoembryonic antigen

    International Nuclear Information System (INIS)

    Kusnierczyk-Glazman, H.; Breborowicz, J.

    1977-01-01

    Goats were immunized with purified carcinoembryonic antigen, and the suitability of the antisera for clinical assays of carcinoembryonic antigen was characterized. Reactivity of equine sera to goat γ-globulin as a precipitating factor in the radioimmunologic double antibody technique was also evaluated. (author)

  11. Copper Cu 64 Anti-CEA Monoclonal Antibody M5A PET in Diagnosing Patients With CEA Positive Cancer

    Science.gov (United States)

    2018-05-04

    Breast Cancer; Colon Cancer; Extrahepatic Bile Duct Cancer; Gallbladder Cancer; Gastrointestinal Cancer; Liver and Intrahepatic Biliary Tract Cancer; Lung Cancer; Metastatic Cancer; Pancreatic Cancer; Rectal Cancer; Thyroid Gland Medullary Carcinoma; Unspecified Adult Solid Tumor, Protocol Specific

  12. Fluorine-18 radiolabeling of low-density lipoproteins: a potential approach for characterization and differentiation of metabolism of native and oxidized low-density lipoproteins in vivo

    International Nuclear Information System (INIS)

    Pietzsch, Jens; Bergmann, Ralf; Rode, Katrin; Hultsch, Christina; Pawelke, Beate; Wuest, Frank; Hoff, Joerg van den

    2004-01-01

    Oxidative modification of low-density lipoprotein (LDL) is regarded as a crucial event in atherogenesis. Assessing the metabolic fate of oxidized LDL (oxLDL) in vivo with radiotracer techniques is hindered by the lack of suitable sensitive and specific radiolabeling methods. We evaluated an improved methodology based on the radiolabeling of native LDL (nLDL) and oxLDL with the positron emitter fluorine-18 ( 18 F) by conjugation with N-succinimidyl-4-[ 18 F]fluorobenzoate ([ 18 F]SFB). We investigated whether radiolabeling of LDL induces adverse structural modifications. Results suggest that radiolabeling of both nLDL and oxLDL using [ 18 F]SFB causes neither additional oxidative structural modifications of LDL lipids and proteins nor alteration of their biological activity and functionality, respectively. Thus, radiolabeling of LDL using [ 18 F]SFB could prove to be a promising approach for studying the kinetics of oxLDL in vivo

  13. Fluorine-18 radiolabeling of low-density lipoproteins: a potential approach for characterization and differentiation of metabolism of native and oxidized low-density lipoproteins in vivo.

    Science.gov (United States)

    Pietzsch, Jens; Bergmann, Ralf; Rode, Katrin; Hultsch, Christina; Pawelke, Beate; Wuest, Frank; van den Hoff, Joerg

    2004-11-01

    Oxidative modification of low-density lipoprotein (LDL) is regarded as a crucial event in atherogenesis. Assessing the metabolic fate of oxidized LDL (oxLDL) in vivo with radiotracer techniques is hindered by the lack of suitable sensitive and specific radiolabeling methods. We evaluated an improved methodology based on the radiolabeling of native LDL (nLDL) and oxLDL with the positron emitter fluorine-18 ((18)F) by conjugation with N-succinimidyl-4-[(18)F]fluorobenzoate ([(18)F]SFB). We investigated whether radiolabeling of LDL induces adverse structural modifications. Results suggest that radiolabeling of both nLDL and oxLDL using [(18)F]SFB causes neither additional oxidative structural modifications of LDL lipids and proteins nor alteration of their biological activity and functionality, respectively. Thus, radiolabeling of LDL using [(18)F]SFB could prove to be a promising approach for studying the kinetics of oxLDL in vivo.

  14. Synthesis of radiolabelled aryl azides from diazonium salts: experimental and computational results permit the identification of the preferred mechanism.

    Science.gov (United States)

    Joshi, Sameer M; de Cózar, Abel; Gómez-Vallejo, Vanessa; Koziorowski, Jacek; Llop, Jordi; Cossío, Fernando P

    2015-05-28

    Experimental and computational studies on the formation of aryl azides from the corresponding diazonium salts support a stepwise mechanism via acyclic zwitterionic intermediates. The low energy barriers associated with both transition structures are compatible with very fast and efficient processes, thus making this method suitable for the chemical synthesis of radiolabelled aryl azides.

  15. Effect of highly radiolabelled 2,4-dinitrochlorobenzene (DNCB) on experimental DNCB contact dermatitis in guinea pigs

    Energy Technology Data Exchange (ETDEWEB)

    Filipp, G [Red Cross Clinic, Dept. of Clinical Immunology and Allergology, Saarbruecken; Biro, G [2. Medical Clinic, Medical School, University of Saarland, Homburg/Saar; Bahmer, F [Clinic of Dermatology, Medical School, University of Saarland, Homburg/Saar; Mitschke, H [Institute of Pathology, Municipal Academic Hospital, Winterberg, Saarbruecken; Lehmann, G [Dept. of Analytical and Biological Chemistry, University of Saarland, Saarbruecken, Federal Republic of Germany

    1984-01-01

    With the aid of epicutaneous application of 2,4-dinitrochlorobenzene (DNCB) solution in acetone, we induced a cutaneous allergic reaction of the delayed type. Our question was whether the development of the DNCB cutaneous sensitivity could be suppressed by highly radiolabelled DNCB. On the basis of the clonal selection theory and our own results with other in vivo-experimental animal models, one could suppose that the highly radiolabelled DNCB as haptens binds to the Ig-membrane receptors of the genetically determined T-lymphocyte clone, and that the conjugated radioactivity (/sup 125/I) causes a selective radioactive damage to this competent T-lymphocyte subpopulation. By means of intracardially applied radiolabelled DNCB, we are able to induce either complete or very significant suppression of the cutaneous DNCB immune response. In the second experiment, the highly radiolabelled DNCB was not able to inhibit sensitization to a simultaneously applied 4-ethoxy-methylene-2-phenyl-oxazolone (oxazolone). This result clearly demonstrates the antigen specificity of this form of immune suppression.

  16. Radiolabeling optimization and characterization of (68)Ga labeled DOTA-polyamido-amine dendrimer conjugate - Animal biodistribution and PET imaging results.

    Science.gov (United States)

    Ghai, Aanchal; Singh, Baljinder; Panwar Hazari, Puja; Schultz, Michael K; Parmar, Ambika; Kumar, Pardeep; Sharma, Sarika; Dhawan, Devinder; Kumar Mishra, Anil

    2015-11-01

    The present study describes the optimization of (68)Ga radiolabeling with PAMAM dendrimer-DOTA conjugate. A conjugate (PAMAM-DOTA) concentration of 11.69µM, provided best radiolabeling efficiency of more than 93.0% at pH 4.0, incubation time of 30.0min and reaction temperature ranging between 90 and 100°C. The decay corrected radiochemical yield was found to be 79.4±0.01%. The radiolabeled preparation ([(68)Ga]-DOTA-PAMAM-D) remained stable (radiolabeling efficiency of 96.0%) at room temperature and in serum for up to 4-h. The plasma protein binding was observed to be 21.0%. After intravenous administration, 50.0% of the tracer cleared from the blood circulation by 30-min and less than 1.0% of the injected activity remained in blood by 1.0h. The animal biodistribution studies demonstrated that the tracer excretes through the kidneys and about 0.33% of the %ID/g accumulated in the tumor at 1h post injection. The animal organ's biodistribution data was supported by animal PET imaging showing good 'non-specific' tracer uptake in tumor and excretion is primarily through kidneys. Additionally, DOTA-PAMAM-D conjugation with αVβ3 receptors targeting peptides and drug loading on the dendrimers may improve the specificity of the (68)Ga labeled product for imaging and treating angiogenesis respectively. Copyright © 2015 Elsevier Ltd. All rights reserved.

  17. Effect of highly radiolabelled 2,4-dinitrochlorobenzene (DNCB) on experimental DNCB contact dermatitis in guinea pigs

    International Nuclear Information System (INIS)

    Filipp, G.; Biro, G.; Bahmer, F.; Mitschke, H.; Lehmann, G.

    1984-01-01

    With the aid of epicutaneous application of 2,4-dinitrochlorobenzene (DNCB) solution in acetone, we induced a cutaneous allergic reaction of the delayed type. Our question was whether the development of the DNCB cutaneous sensitivity could be suppressed by highly radiolabelled DNCB. On the basis of the clonal selection theory and our own results with other in vivo-experimental animal models, one could suppose that the highly radiolabelled DNCB as haptens binds to the Ig-membrane receptors of the genetically determined T-lymphocyte clone, and that the conjugated radioactivity ( 125 I) causes a selective radioactive damage to this competent T-lymphocyte subpopulation. By means of intracardially applied radiolabelled DNCB, we are able to induce either complete or very significant suppression of the cutaneous DNCB immune response. In the second experiment, the highly radiolabelled DNCB was not able to inhibit sensitization to a simultaneously applied 4-ethoxy-methylene-2-phenyl-oxazolone (oxazolone). This result clearly demonstrates the antigen specificity of this form of immune suppression. (author)

  18. Radiolabeling of intact dosage forms by neutron activation: effects on in vitro performance

    International Nuclear Information System (INIS)

    Parr, A.; Jay, M.

    1987-01-01

    Compressed tablets containing various quantities of stable isotopes of Ba, Er, and Sm for use in neutron activation studies were evaluated for the effect of stable isotope incorporation on tablet hardness and disintegration times. At concentrations likely to be used in scintigraphic studies employing neutron activation as a radiolabeling method, no significant effect on in vitro parameters were observed. While the incorporation of stable isotopes influenced tablet hardness to a greater degree than disintegration time, irradiation of tablets in a neutron flux of 4.4 x 10(13) n/cm2 sec had a direct effect on tablet disintegration time. Thus, future neutron activation studies should focus on minimizing the amount of stable isotope to be incorporated with the formulation while using the shortest feasible irradiation time

  19. Microbial uptake of radiolabeled substrates: estimates of growth rates from time course measurements

    International Nuclear Information System (INIS)

    Li, W.K.W.

    1984-01-01

    The uptake of [ 3 H]glucose and a mixture of 3 H-labeled amino acids was measured, in time course fashion, in planktonic microbial assemblages of the eastern tropical Pacific Ocean. The average generation times of those portions of the assemblages able to utilize these substrates were estimated from a simple exponential growth model. Other workers have independently used this model in its integrated or differential form. A mathematical verification and an experimental demonstration of the equivalence of the two approaches are presented. A study was made of the size distribution of heterotrophic activity, using time course measurements. It was found that the size distribution and the effect of sample filtration before radiolabeling were dependent on time of incubation. In principle, it was possible to ascribe these time dependences to differences in th specific growth rate and initial standing stock of the microbial assemblages. 33 references

  20. Maternal-fetal distribution studies of two radiolabeled compounds in miniature Hormel pigs

    International Nuclear Information System (INIS)

    Ikeda, G.J.; Michel, T.C.; Miller, E.; Sager, A.O.; Sapienza, P.P.

    1986-01-01

    Distribution patterns of two radiolabeled compounds were determined in miniature Hormel pigs and their litters late in pregnancy. Seven sows (45 fetuses) were administered (1- 14 C) acrylamide (5 mg/kg IV) and four sows (30 fetuses) were administered (N-methyl- 14 C) betaine (5 mg/kg IV). Acrylamide was distributed readily to both maternal and fetal tissues; a placental factor of 31% was calculated. A blood/brain factor was insignificant in sows and nonexistent in fetal pigs. The placental factor for betaine was calculated to be 97.8% for maternal and fetal tissues. The blood/brain factor was 89% in sows but nonexistent in fetuses. Maternal liver and kidney accounted for the highest levels of radioactivity for both compounds. Although placenta protects the minipig fetus to some degree from substances in maternal blood, the fetal brain is unprotected from possible injury or damage if a foreign substance enters the fetal blood stream

  1. Intracellular uptake and distribution of radiolabeled iodovinly deoxy uridine (IVDU) for gene therapy monitoring

    Energy Technology Data Exchange (ETDEWEB)

    Choi, T. H.; Lee, T. S.; Lee, S. J.; Woo, K. S.; Jeon, W. S.; Choi, C. W.; Yim, S. M. [KCCH, Seoul (Korea, Republic of)

    2001-05-01

    We have evaluated a useful synthetic radiolabeled nucleoside substrate, (E)-5-2(2-[125I] idodovinyl) uracil deoxyuridine (IVDU), for herpes simplex virus type-1 thymidine kinase (HSV1-TK). Cellular uptake of these labeled compounds was observed in vitro. low uptake was showed in MCA cell line and high uptake was observed in Herpes simplex virus type-1 thymidine kinase(HSV1-tk) gene tranduced MCA(MCA-tk) cell line. Intracellular distribution of {sup 125}I-IVDU was differently occured in the MCA and MCA-TK cell line, respectively. Main distribution of MCA cells is in cytosol, and that of MCA-TK cells was in mitochondria and nuclei. For HSV1-tk system. We confirmed that IVDU was incorporated into DNA synthesis.

  2. 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).

  3. Radiolabeled 9- or 10-monoiodostearic acid and 9- or 10-monoiodostearyl carnitine: Pt. 1

    International Nuclear Information System (INIS)

    Reed, K.W.; Ueda, C.T.; Murray, W.J.; Augustine, S.C.

    1989-01-01

    The purpose of this investigation was to synthesize and purify radiolabeled 9- or 10-monoiodostearyl carnitine for potential use as a perfusion and metabolic imaging agent for the heart. Oleic acid was iodinated via a free radical addition reaction of Hl across the double bond to give 9- or 10-monoiodostearic acid which in turn was esterified with carnitine. The identity of 9- or 10-monoiodostearic acid and 9-or 10-monoiodostearyl carnitine was determined using nuclear magnetic resonance (NMR), infrared (i.r.), ultraviolet (u.v.), and mass spectroscopy. The purity of the fatty acid and carnitine ester was established by thin layer chromatography. 9- or 10-Monoiodo[ 125 I]stearic acid and 9- or 10-monoiodo[ 125 I]stearyl carnitine were synthesized via the isotopic exchange of 125 I for cold iodine bonded to 9- or 10-monoiodostearic acid and 9- or 10-monoiodostearyl carnitine. (author)

  4. Echinococcus granulosus: the potential use of specific radiolabelled antibodies in diagnosis by immunoscintigraphy

    Energy Technology Data Exchange (ETDEWEB)

    Rogan, M.T.; Morris, D.L.; Pritchard, D.I.; Perkins, A.C. (Nottingham Univ. (UK))

    1990-05-01

    Diagnosis of hydatid disease in man is frequently dependent on the imaging of cysts in situ by techniques such as ultrasonography and CAT scans. Such methods are useful but are not specific and can lead to errors in diagnosis. The present work reports preliminary experiments on the development of a specific imaging technique for hydatid cysts using radiolabelled antibodies. A purified preparation of antigen B of hydatid fluid was used to raise polyclonal antisera in rabbits and the resulting affinity-purified IgG labelled with {sup 131}I. Gerbils with an established Echinococcus granulosus infection were injected intraperitoneally with the labelled antibody and imaged 48 h later with a gamma camera. Hydatid cysts could be identified within the peritoneal cavity and post-mortem assessment of activity showed the cysts to contain approximately four times as much activity as the surrounding organs thereby indicating successful targeting of the antibody to the cysts. (author).

  5. Echinococcus granulosus: the potential use of specific radiolabelled antibodies in diagnosis by immunoscintigraphy

    International Nuclear Information System (INIS)

    Rogan, M.T.; Morris, D.L.; Pritchard, D.I.; Perkins, A.C.

    1990-01-01

    Diagnosis of hydatid disease in man is frequently dependent on the imaging of cysts in situ by techniques such as ultrasonography and CAT scans. Such methods are useful but are not specific and can lead to errors in diagnosis. The present work reports preliminary experiments on the development of a specific imaging technique for hydatid cysts using radiolabelled antibodies. A purified preparation of antigen B of hydatid fluid was used to raise polyclonal antisera in rabbits and the resulting affinity-purified IgG labelled with 131 I. Gerbils with an established Echinococcus granulosus infection were injected intraperitoneally with the labelled antibody and imaged 48 h later with a gamma camera. Hydatid cysts could be identified within the peritoneal cavity and post-mortem assessment of activity showed the cysts to contain approximately four times as much activity as the surrounding organs thereby indicating successful targeting of the antibody to the cysts. (author)

  6. Contamination of pig carcasses with scalding water studied with a radiolabelled colloid

    Energy Technology Data Exchange (ETDEWEB)

    Jones, E; Nilsson, T; Ekman, L; Oestlund, K [Sveriges Lantbruksuniversitet, Uppsala. Dept. of Clinical Chemistry; Sveriges Lantbruksuniversitet, Uppsala. Abt. fuer Lebensmittelhygiene; Schwedisches Fleischforschungszentrum, Kaevlinge

    1979-10-01

    Swine carcasses at slaughter are normally scalded after bleeding, i.e. immersed in a hot-water-tank. The present study was made to investigate whether during this treatment scalding water enters the severed vessels via the stick wound and contaminates the carcass. Five experimental pigs were slaughtered and immersed in a scalding vat containing water with a dispersed radiolabelled colloid, sup(99m)Tc-sulphide. After scalding muscles and other tissues from various parts of the body were examined for radioactivity. Scalding water (radioactivity) could be demonstrated in tissues from all investigated parts of the carcass. The highest amounts were found in the lungs and in the large blood vessels. The hygienic significance of the findings is discussed.

  7. Use of a microwave cavity to reduce reaction times in radiolabelling with [11C]cyanide

    International Nuclear Information System (INIS)

    Thorell, J.-O.; Stone-Elander, S.; Elander, N.

    1992-01-01

    Advantages of using a microwave cavity over thermal treatment are demonstrated for radiolabelling reactions with [ 11 C]cyanide. For comparison purposes, two literature syntheses involving typical cyanide chemistry at rather vigorous conditions were investigated: cyano-de-halogenation with subsequent hydrolysis of the nitrile and the Bucher-Strecker synthesis of an aromatic amino acid. Comparable yields were obtained with intensities <100 W in reaction times that were 1/15 to 1/20th those used in thermal methods. Even rates of slower nucleophilic substitutions could be increased by manipulating the polarity of the medium. For the short-lived radionuclide carbon-11, such time gains result in radioactivity gains at the end-of-synthesis on the order of 70-100%. (Author)

  8. Radiolabelling of sperm cells with 99mTc-HM-PAO

    International Nuclear Information System (INIS)

    Balogh, L.; Szasz, F.; Janoki, Gy.; Zoldag, L.; Huszenicza, Gy.

    1992-01-01

    The study of the influence of labelling volume on the labelling efficiency showed decreased yield when the volume was increased. The survival rate was unchanged over 0.5 ml of reaction volume. During labelling procedure only a few cells (6%) survived in the incubation volume was less than 0.4 ml. Changing the incubation time the radiolabelling yield increased for 10 minutes, and thereafter practically did not change. The optimum conditions of sperm labelling yielded a high labelling efficiency (70-80%) and survival rate (50-60%). The 99m Tc-HM-PAO labelled sperm cells seem to be suitable to study the in vivo and in vitro sperm transport. (author) 14 refs.; 5 figs.; 2 tabs

  9. Synthesis and Radiolabeling of Modified Peptides Attached to Heterocyclic Rings and Their Possible Medical Applications

    International Nuclear Information System (INIS)

    Shams El-Din, H.A.A.

    2012-01-01

    Keeping in mind the pharmacological potential of heterocyclic rings as well as the advantage of biodegradability and biocompatibility of amino acids/peptides, in this thesis we were prompted for the following: 1. Synthesis of novel dipeptide derivatives coupled with different heterocyclic rings (pyridine, 1,2,4-triazol-pyridine, 1,3,4-oxadiazolpyridine and tetrazol-pyridine rings). 2. Characterization of the synthesized compounds on the basis of their spectral data (IR, Mass and 1 H-NMR spectra). 3. Study their antimicrobial activity as one of their expected biological activities. 4. Study the radioiodination of some synthesized dipeptide derivatives. 5. Study the biodistribution of the radiolabeled compounds in normal mice as preliminary studies for the possibility of using them as agents for imaging and treatment.

  10. 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

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

    International Nuclear Information System (INIS)

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

    1990-01-01

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

  12. Comparative study between phenol and imidazole derivatives in radiolabeling of some steroid hormones

    International Nuclear Information System (INIS)

    Sallam, Kh.M.

    2010-01-01

    A phenol or imidazole ring is rarely present in steroid hormones, So, the molecule of steroid hormone requires chemical modification by addition of an iodinable residue like phenol or imedazole. So that the comparative study between phenol derivatives, include tyrosine methyl ester (TME) and tyramine, and imidazole derivatives, like histamine and histedine methyl ester (HME), for radiolabeling of some steroid hormones include estradiol and testosterone is the aim of the present study. The conjugation step was carried using mixed anhydride method and followed by radioiodination using iodogen as an oxidizing agent. Purification step was carried out using high performance liquid chromatography (HPLC). Optimization and validation of the tracer were carried out. Immunoreactivity of the all obtained tracers was check by using specific polyclonal antibodies. The results indicated that imidazols derivatives are more suitable from immunoreactivity view and storage period.

  13. Preparation of crotalus venom radiolabeled with technetium99m as a tool for biodistribution study

    International Nuclear Information System (INIS)

    Pujatti, Priscilla Brunelli; Santos, Raquel Gouvea dos; Simal, Carlos Jorge Rodrigues

    2005-01-01

    Technetium- 99m ( 99m Tc) has been the radionuclide of choice for nuclear medicine procedures and experimental research. Because of its optimal nuclear properties, 99m Tc is suitable for high efficiency detection with the advantage of reduced radiological waste. Crotalus venom (CV) has been shown to reduce tumors in clinical studies and tissue distribution studies are very important for clinical use. The goal of this work was to obtain CV labeled with 99m Tc which preserves its biological activity. After labeling, biological activity was assessed by hemolytic activity evaluation. Labeled and crude venom caused indirect hemolysis provided that the incubation medium contained an exogenous source of lecithin. High yield radiolabeled-CV was obtained and biological activity was preserved. The results suggest that 99m Tc-CV can be a useful tool for biodistribution studies. (author)

  14. Tc-99m Radiolabeled Alendronate Sodium Microemulsion: Characterization and Permeability Studies Across Caco-2 Cells.

    Science.gov (United States)

    Elitez, Yetkin; Ekinci, Meliha; Ilem-Ozdemir, Derya; Gundogdu, Evren; Asikoglu, Makbule

    2018-01-01

    Alendronate sodium (ALD) is used orally but it is poorly absorbed from the gastrointestinal (GI) tract. For this reason, microemulsion system was chosen to evaluate ALD from the GI tract after oral delivery. This study was aimed to prepare water-in-oil (w/o) microemulsion formulation of ALD and evaluate the permeability of ALD microemulsion from Caco-2 cell lines with radioactive and nonradioactive studies. The ALD microemulsion was developed by using pseudo-ternary phase diagram and composed of Soybean oil, Colliphor EL, Tween 80, Transcutol and distilled water. The prepared ALD microemulsion was characterized by physical appearance, droplet size, viscosity, pH, electrical conductivity and refractive index. The stability of the formulation was investigated for 6 months at 25±2°C/60±5% of relative humidity (RH) as well as at 40±2°C/75±5% RH. After that 1 mg of ALD was radiolabeled with 99mTc and added to microemulsion. The permeability studies were performed with both 99mTc-ALD microemulsion and ALD microemulsion. The experimental results suggested that ALD microemulsion presented adequate stability with droplet size varying from 37.8±0.9 to 39.9±1.2 nm during incubation time. In addition, ALD microemulsion was radiolabeled with high labeling efficiency (>95%). In a non-radioactive study, ALD permeability was found to be 45 µg.mL-1 and microemulsion has high permeability percentage when compared to another study. The novel w/o microemulsion formulation has been developed for oral delivery of ALD. Based on the results, permeability of ALD could be significantly improved by the microemulsion formulation. In addition, 99mTc-ALD microemulsion in capsule can be used for bone disease treatment and diagnosis. Copyright© Bentham Science Publishers; For any queries, please email at epub@benthamscience.org.

  15. Radiolabeling, quality control and radiochemical purity assessment of 99mTc-HYNIC-TOC

    International Nuclear Information System (INIS)

    Melero, Laura T.U.H.; Araujo, Elaine B.; Mengatti, Jair

    2009-01-01

    Somatostatine receptors are widely expressed by several tumors, especially of the neuroendocrine origin. In vivo images of these tumors using radiolabeled somatostatine analogues became a useful clinical tool in oncology. The aim of this work was the radiolabeling of the somatostatine analogue HYNIC-TOC with 99mTc as well as the evaluation of the radiochemical stability and quality control of labeled complex. 99mTc-HYNIC-TOC was produced by labeling conditions using 20 μg of peptide, 20 mg of tricine and 10 mg of EDDA as coligands, 1110 MBq of 99mTc (99Mo-99mTc IPEN-TEC generator) and 15 μg of SnCl 2 .2H 2 O. The reaction proceeds for 10 minutes at boiling water bath. Radiochemical purity of labeled preparation was evaluated by different chromatographic systems: ITLC-SG in methanol:ammonium acetate (1:1); TLC-SG in sodium citrate buffer 0.1 N pH 5.0 and methylethylketone, and HPLC employing column C-18, 5 μm, 4.6 mm x 250 mm, UV (220 nm), radioactivity detectors, 1 mL/minute flow of acetonitrile and trifluoroacetic acid solution 0.1 %. Labeled compound has been found radiochemically stable for 5 hours and radiochemical purity was higher than 90 %. The thin layer chromatographic systems enabled the separation of radiochemical species presented in the labeled mixture as well as HPLC system. The labeling procedure studied resulted in high radiochemical yield and easy preparation. Future works include the preparation of a lyophilized reagent to make feasible the preparation of 99mTc-HYNIC-TOC at nuclear medicine services in order to study the clinical potential of the radiopharmaceutical in diagnostic and staging of neuroendocrine tumors. (author)

  16. Evaluation of di-amino phenol substituted EDTA for use in radiolabelling proteins with 64Cu

    International Nuclear Information System (INIS)

    Schmidt, P.F.; Smith, S.V.; DiBartolo, N.M.

    1996-01-01

    This study involves a high yielding synthesis of a novel di-amino-phenol substituted EDTA (DAHA-EDTA) ligand and its radiolabelling chemistry with 64 Cu produced at the National Medical Cyclotron (NMC). High activity levels (up to 59.2 GBq EOB) of 64 Cu is co-produced during the production of 67 Ga from enriched 68 Zn. Waste eluent from the NMC 67 Ga production was evaporated to dryness and found to contain by products such as 57 Ni, 57 Co, 64 Cu, 67 Cu and 55 Co. A new method involving low acid concentration aqueous/organic mixtures with an anion exchange (AG 1-X8, BioRad) have been used to isolate the carrier-free 64 Cu. The specific activity of the 64 Cu (5 x 10 14 Bq/g) was found to be higher than that produce by Australian radioisotopes (ARI). The synthesis of the ligand involves the refluxing of EDTA anhydride in the presence of 4-nitro-2-amino-phenol in acetonitrile to produce the di-nitro derivative (DNHA- EDTA) in > 95% yield. The DNHA-EDTA is then reduced in the presence of activated palladium charcoal with sodium borohydride under an inert atmosphere at room temperature. The reaction mixture was acidified and the catalyst removed to obtain the final product, DAHA-EDTA. Labelling of proteins (B72.3, DD-3B6/22 and streptavidin) has been achieved with the DAHA-EDTA ligand. The reaction mixture is left to incubate for 1 h at 37 deg C and radiolabelled protein is then isolated using size exclusion chromatography

  17. Radiolabeling, quality control and radiochemical purity assessment of {sup 99m}Tc-HYNIC-TOC

    Energy Technology Data Exchange (ETDEWEB)

    Melero, Laura T.U.H.; Araujo, Elaine B.; Mengatti, Jair [Instituto de Pesquisas Energeticas e Nucleares (IPEN/CNEN-SP), Sao Paulo, SP (Brazil)

    2009-07-01

    Somatostatine receptors are widely expressed by several tumors, especially of the neuroendocrine origin. In vivo images of these tumors using radiolabeled somatostatine analogues became a useful clinical tool in oncology. The aim of this work was the radiolabeling of the somatostatine analogue HYNIC-TOC with 99mTc as well as the evaluation of the radiochemical stability and quality control of labeled complex. 99mTc-HYNIC-TOC was produced by labeling conditions using 20 {mu}g of peptide, 20 mg of tricine and 10 mg of EDDA as coligands, 1110 MBq of 99mTc (99Mo-99mTc IPEN-TEC generator) and 15 {mu}g of SnCl{sub 2}.2H{sub 2}O. The reaction proceeds for 10 minutes at boiling water bath. Radiochemical purity of labeled preparation was evaluated by different chromatographic systems: ITLC-SG in methanol:ammonium acetate (1:1); TLC-SG in sodium citrate buffer 0.1 N pH 5.0 and methylethylketone, and HPLC employing column C-18, 5 {mu}m, 4.6 mm x 250 mm, UV (220 nm), radioactivity detectors, 1 mL/minute flow of acetonitrile and trifluoroacetic acid solution 0.1 %. Labeled compound has been found radiochemically stable for 5 hours and radiochemical purity was higher than 90 %. The thin layer chromatographic systems enabled the separation of radiochemical species presented in the labeled mixture as well as HPLC system. The labeling procedure studied resulted in high radiochemical yield and easy preparation. Future works include the preparation of a lyophilized reagent to make feasible the preparation of 99mTc-HYNIC-TOC at nuclear medicine services in order to study the clinical potential of the radiopharmaceutical in diagnostic and staging of neuroendocrine tumors. (author)

  18. Intrinsically radiolabelled [(59)Fe]-SPIONs for dual MRI/radionuclide detection.

    Science.gov (United States)

    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 [(59)Fe]-superparamagnetic iron oxide nanoparticles ([(59)Fe]-SPIONs) as a proof of concept for an intrinsic dual probe strategy. (59)Fe was incorporated into Fe3O4 nanoparticle crystal lattice with 92±3% efficiency in thermal decomposition synthesis. Multidentate poly(acrylic acid)-dopamine-poly(ethylene-glycol-2000) (PAA-DOP-PEG) ligands were designed and synthesized based on facile EDC chemistry and utilized to functionalize the [(59)Fe]-SPIONs. The transverse relaxivity of [(59)Fe]-SPIONs (97±3 s(-1)mM(-1)) was characterized and found to be similar to non-radioactive SPIONs (72±10 s(-1)mM(-1)), indicating that (59)Fe incorporation does not alter the SPIONs' MRI contrast properties. [(59)Fe]-SPIONs were used to evaluate the nanoparticle biodistribution by ex vivo gamma counting and MRI. Nude mice (n=15) were injected with [(59)Fe]-SPIONs and imaged at various time points with 7T small animal MRI scanner. Ex vivo biodistribution was evaluated by tissue-based gamma counting. MRI signal contrast qualitatively correlates with the %ID/g of [(59)Fe]-SPIONs, with high contrast in liver (45±6%), medium contrast in kidneys (21±5%), and low contrast in brain (4±6%) at 24 hours. This work demonstrates the synthesis and in vivo application of intrinsically radiolabeled [(59)Fe]-SPIONs for bimodal detection and provides a proof of concept for incorporation of both gamma- and positron-emitting inorganic radionuclides into the core of metal based MRI contrast agent nanoparticles.

  19. Botulinum neurotoxin type A radiolabeled at either the light or the heavy chain

    International Nuclear Information System (INIS)

    Dekleva, M.L.; DasGupta, B.R.; Sathyamoorthy, V.

    1989-01-01

    Botulinum neurotoxin (NT) has two distinct structural regions called L and H chains (approximately 50 and approximately 100 kDa, respectively). Although the H chain is responsible for binding of the NT to neuronal cells, it is not known which of the subunits is internalized and therefore responsible for causing the blockage of acetylcholine release in susceptible neuronal cells. In this report we describe for the first time the preparation of type A NT which is selectively radiolabeled at either the L or the H chain subunit. Such NT preparations will be useful as tools for determining the distribution of L and H chains in poisoned neuronal cells and the role that each subunit plays in inducing toxicity. The L and H chains of the NT (approximately 150 kDa) were separated, purified, and then individually radiolabeled by reductive methylation of the lysine residues using [3H]- or [14C]formaldehyde. The labeled L and H chains were reconjugated with the complementary unlabeled L and H chains. Formation of -S-S- and noncovalent bonds between the L and H chains regenerated the approximately 150 kDa NT. Autoradiographs of sodium dodecyl sulfate polyacrylamide gels confirmed that each reconstituted NT preparation was labeled at only one subunit chain. NT selectively labeled at either the L or the H chain had specific radioactivities of ca. 25-30 and 45-55 microCi/mumol, respectively, and toxicity (mouse LD50/mg protein) values of 2.2 +/- 1.1 X 10(7) and 3.0 +/- 1.0 X 10(7), respectively. A linear increase in the specific radioactivity of L and H chain subunits was observed with increasing concentrations of 3H- or 14C-labeled formaldehyde in the reaction mixture and with increasing concentrations of L or H chain in the reaction mixture

  20. Synthesis and radiolabelling of AG957 a potential tyrphostin PET radiotracer

    International Nuclear Information System (INIS)

    Ackermann, U.; Tochon-Danguy, H.J.; Sachinidis, J.; Burgess, A.W.; Scott, A.M.

    2000-01-01

    Full text: Signalling of tyrosine kinases is a critical component of intracellular regulation of growth and function. AG957 is an inhibitor of the c-ABL tyrosine kinase found in chronic myeloid leukemia, and the labelling of AG957 with a PET radiotracer would allow for the in vivo mapping of this receptor-kinase. Synthesis of the normethyl precursor of the tyrosine kinase inhibitor AG957 has been achieved by condensation of p-amino benzoic acid with 2,6 dihydroxy benzaldehyde and subsequent reduction of the imino function with sodium cyanoborohydride. The radiolabeling of this precursor using 11 C-methyliodide in basic conditions gave unsatisfactory yields because of decomposition of the starting material. We have therefore investigated the formation of 11 C-methyl esters using 11 Cmethanol and free carboxylic acids in the presence of either trimethylsilylchloride or boron trifluoride etherate as catalyst. P-amino benzoic acid, benzoic acid and salicylic acid were used as model compounds. Boron trifluoride etherate proved to be superior to trimethylsilylchloride giving good yields of the esters of the respective carboxylic acids when reacted with 11 C-methanol at 150 deg C. However, when this method was applied to desmethyl AG957, none of the desired product was obtained due to decomposition of the precursor at high temperatures. In light of these results we are planning to investigate the irreversible transesterification of enol esters with 11 C-methanol in the presence of a tin catalyst. This reaction is known to proceed smoothly at lower temperatures and should enable us to radiolabel the tyrosine kinase inhibitor 11 C-AG957. Copyright (2000) The Australian and New Zealand Society of Nuclear Medicine Inc

  1. The use of 14C-FIAU to predict bacterial thymidine kinase presence: Implications for radiolabeled FIAU bacterial imaging

    International Nuclear Information System (INIS)

    Peterson, Kristin L.; Reid, William C.; Freeman, Alexandra F.; Holland, Steven M.; Pettigrew, Roderic I.; Gharib, Ahmed M.; Hammoud, Dima A.

    2013-01-01

    Currently available infectious disease imaging techniques cannot differentiate between infection and sterile inflammation or between different types of infections. Recently, radiolabeled FIAU was found to be a substrate for the thymidine kinase (TK) enzyme of multiple pathogenic bacteria, leading to its translational use in the imaging of bacterial infections. Patients with immunodeficiencies, however, are susceptible to a different group of pathogenic bacteria when compared to immunocompetent subjects. In this study, we wanted to predict the usefulness of radiolabeled FIAU in the detection of bacterial infections commonly occurring in patients with immunodeficiencies, in vitro, prior to attempting in vivo imaging with 124 I-FIAU-PET. Methods: We obtained representative strains of bacterial pathogens isolated from actual patients with genetic immunodeficiencies. We evaluated the bacterial susceptibility of different strains to the effect of incubation with FIAU, which would implicate the presence of the thymidine kinase (TK) enzyme. We also incubated the bacteria with 14 C-FIAU and consequently measured its rate of incorporation in the bacterial DNA using a liquid scintillation counter. Results: Unlike the other bacterial strains, the growth of Pseudomonas aeruginosa was not halted by FIAU at any concentration. All the tested clinical isolates demonstrated different levels of 14 C-FIAU uptake, except for P. aeruginosa. Conclusion: Radiolabeled FIAU has been successful in delineating bacterial infections, both in preclinical and pilot translational studies. In patients with immunodeficiencies, Pseudomonas infections are commonly encountered and are usually difficult to differentiate from fungal infections. The use of radiolabeled FIAU for in vivo imaging of those patients, however, would not be useful, considering the apparent lack of TK enzyme in Pseudomonas. One has to keep in mind that not all pathogenic bacteria possess the TK enzyme and as such will not all

  2. Optimised labeling, preclinical and initial clinical aspects of CCK-2 receptor-targeting with 3 radiolabeled peptides

    International Nuclear Information System (INIS)

    Breeman, Wouter A.P.; Froeberg, A.C.; Blois, E. de; Gameren, A. van; Melis, M.; Jong, M. de; Maina, T.; Nock, B.A.; Erion, J.L.; Maecke, H.R.; Krenning, E.P.

    2008-01-01

    Medullary thyroid carcinoma (MTC) expresses CCK-2 receptors. 111 In-labeled DOTA-DGlu-Ala-Tyr-Gly-Trp-Met-Asp-Phe-NH 2 (DOTA-MG11), DOTA-DAsp-Tyr-Nle-Gly-Trp-Nle-Asp-Phe-NH 2 (DOTA-CCK), and 99m Tc-labeled N 4 -Gly-DGlu-(Glu) 5 -Ala-Tyr-Gly-Trp-Met-Asp-Phe-NH 2 ( 99m Tc-Demogastrin 2) are analogs developed for CCK-2 receptor-targeted scintigraphy. All 3 radiolabeled analogs were selected on the basis of their high CCK-2 receptor affinity and their good in vitro serum stability, with in vitro serum t 1/2 values of several hours. Radiolabeling of DOTA-peptides with 111 In requires a heating procedure, typically in the range of 80 deg. - 100 deg. C up to 30 min. Following this procedure with DOTA-MG11 resulted in a >98 % incorporation of 111 In, however, with a radiochemical purity (RCP) of 111 In involved 5 min heating at 80 deg. C and led to an incorporation of 111 In of >98 %. In addition, all analogs were radiolabeled in the presence of quenchers to prevent radiolysis and oxidation resulting in a RCP of >90 %. All 3 radiolabeled analogs were i.v. administered to 6 MTC patients: radioactivity cleared rapidly by the kidneys, with no significant differences in the excretion pattern of the 3 radiotracers. All 3 radiolabeled analogs exhibited a low in vivo stability in patients, as revealed during analysis of blood samples, with the respective t 1/2 found in the order of minutes. In patient blood, the rank of radiopeptide in vivo stability was: 99m Tc-Demogastrin 2 (t 1/2 10-15 min)> 111 In-DOTA-CCK (t 1/2 ∼5-10 min)> 111 In-DOTA-MG11 (t 1/2 <5 min)

  3. Evaluation of single amino acid chelate derivatives and regioselective radiolabelling of a cyclic peptide for the urokinase plasminogen activator receptor

    Energy Technology Data Exchange (ETDEWEB)

    Armstrong, Andrea F.; Lemon, Jennifer A. [McMaster Institute for Applied Radiation Sciences, McMaster University, ON, L8S 4M1 (Canada); Czorny, Shannon K. [McMaster Institute for Applied Radiation Sciences, McMaster University, ON, L8S 4M1 (Canada); Juravinski Cancer Centre, Hamilton, ON, L8V 5C2 (Canada); Singh, Gurmit [Juravinski Cancer Centre, Hamilton, ON, L8V 5C2 (Canada); Valliant, John F. [Department of Chemistry, McMaster University, Hamilton, ON, L8S 4M1 (Canada); Department of Medical Physics and Applied Radiation Sciences, McMaster University, Hamilton, ON, L8S 4M1 (Canada)], E-mail: valliant@mcmaster.ca

    2009-11-15

    Introduction: The aim of this work was to investigate the relative radiolabelling kinetics and affinity of a series of ligands for the [{sup 99m}Tc(CO){sub 3}]{sup +} core, both in the absence and in the presence of competing donors. This information was used to select a suitable ligand for radiolabelling complex peptide-based targeting vectors in high yield under mild conditions. Methods: A series of {alpha}-N-Fmoc-protected lysine derivatives bearing two heterocyclic donor groups at the {epsilon}-amine (, 2-pyridyl; , quinolyl; , 6-methoxy-2-pyridyl; 1d, 2-thiazolyl; 1e, N-methylimidazolyl; , 3-pyridyl) were synthesized and labelled with {sup 99m}Tc. A resin-capture purification strategy for the separation of residual ligand from the radiolabelled product was also developed. The binding affinities of targeted peptides 4, 5a and 5b for uPAR were determined using flow cytometry. Results: Variable temperature radiolabelling reactions using - and [{sup 99m}Tc(CO){sub 3}]{sup +} revealed optimal kinetics and good selectivity for compounds and 1d; in the case of , 1d, and 1e, the labelling can be conducted at ambient temperature. The utility of this class of ligands was further demonstrated by the radiolabelling of a cyclic peptide that is known to target the serine protease receptor uPAR; essentially quantitative incorporation of {sup 99m}Tc occurred exclusively at the SAAC site, despite the presence of a His residue, and without disruption of the disulfide bond. Conclusion: A series of single amino acid chelate (SAAC) ligands have been evaluated for their ability to incorporate {sup 99m}Tc into peptides. The lead agent to emerge from this work is the thiazole SAAC derivative 1d which has demonstrated the ability to regioselectively label the widest range of peptides.

  4. [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

  5. Radiolabelling of glycosylated MFE-23::CPG2 fusion protein (MFECP1) with 99mTc for quantitation of tumour antibody-enzyme localisation in antibody-directed enzyme pro-drug therapy (ADEPT).

    Science.gov (United States)

    Francis, R J; Mather, S J; Chester, K; Sharma, S K; Bhatia, J; Pedley, R B; Waibel, R; Green, A J; Begent, R H J

    2004-08-01

    MFECP1 is a glycosylated recombinant fusion protein composed of MFE-23, a high-affinity anti-carcinoembryonic antigen (CEA) single chain Fv (scFv), fused to the enzyme carboxypeptidase G2 (CPG2), and has been constructed for use in antibody-directed enzyme pro-drug therapy (ADEPT). Radiolabelling of glycosylated MFECP1 with technetium-99m was developed for the purpose of determining tumour localisation of MFECP1 in a phase I ADEPT clinical study. The method used was 99mTc-carbonyl [99mTc(H2O)3(CO)3]+ (abbreviated to TcCO) mediated labelling of 99mTc to the hexahistidine (His) tag of MFECP1. MFECP1 fusion protein was labelled with TcCO under a variety of conditions, and this was shown to be a relatively simple and robust method. Tissue biodistribution was assessed in a CEA-expressing LS174T (human colon carcinoma) nude mouse xenograft model. Tissues were taken at 1, 4 and 6 h for assessment of distribution of radioactivity and for measurement of CPG2 enzyme levels. The amount of radioactivity retained by the tumour proved to be an accurate estimation of actual measured enzyme activity, indicating that this radiolabelling method does not appear to damage the antibody-antigen binding or the enzyme activity of MFECP1. However, correlation between CPG2 enzyme activity and measured radioactivity in liver, spleen and kidney was poor, indicating retention of radioactivity in non-tumour sites but loss of enzyme activity. The high retention of technetium radioisotope in normal tissues may limit the clinical applicability of this radiolabelling method for MFECP1; however, these results suggest that this technique does have applicability for measuring the biodistribution of His-tagged recombinant proteins.

  6. Radiolabelling of glycosylated MFE-23::CPG2 fusion protein (MFECP1) with 99mTc for quantitation of tumour antibody-enzyme localisation in antibody-directed enzyme pro-drug therapy (ADEPT)

    International Nuclear Information System (INIS)

    Francis, R.J.; Chester, K.; Sharma, S.K.; Bhatia, J.; Pedley, R.B.; Green, A.J.; Begent, R.H.J.; Mather, S.J.; Waibel, R.

    2004-01-01

    MFECP1 is a glycosylated recombinant fusion protein composed of MFE-23, a high-affinity anti-carcinoembryonic antigen (CEA) single chain Fv (scFv), fused to the enzyme carboxypeptidase G2 (CPG2), and has been constructed for use in antibody-directed enzyme pro-drug therapy (ADEPT). Radiolabelling of glycosylated MFECP1 with technetium-99m was developed for the purpose of determining tumour localisation of MFECP1 in a phase I ADEPT clinical study. The method used was 99m Tc-carbonyl [ 99m Tc(H 2 O) 3 (CO) 3 ] + (abbreviated to TcCO) mediated labelling of 99m Tc to the hexahistidine (His) tag of MFECP1. MFECP1 fusion protein was labelled with TcCO under a variety of conditions, and this was shown to be a relatively simple and robust method. Tissue biodistribution was assessed in a CEA-expressing LS174T (human colon carcinoma) nude mouse xenograft model. Tissues were taken at 1, 4 and 6 h for assessment of distribution of radioactivity and for measurement of CPG2 enzyme levels. The amount of radioactivity retained by the tumour proved to be an accurate estimation of actual measured enzyme activity, indicating that this radiolabelling method does not appear to damage the antibody-antigen binding or the enzyme activity of MFECP1. However, correlation between CPG2 enzyme activity and measured radioactivity in liver, spleen and kidney was poor, indicating retention of radioactivity in non-tumour sites but loss of enzyme activity. The high retention of technetium radioisotope in normal tissues may limit the clinical applicability of this radiolabelling method for MFECP1; however, these results suggest that this technique does have applicability for measuring the biodistribution of His-tagged recombinant proteins. (orig.)

  7. Radiolabeling procedure, quality control and stability of {sup 99m}Tc-labeled chondroitin sulfate: A new approach of targeting osteoarthritis

    Energy Technology Data Exchange (ETDEWEB)

    Sobal, Grazyna [Department of Nuclear Medicine, Medical University of Vienna, A-1090 Vienna, Waehringer Guertel 18-20 (Austria)], E-mail: Grazyna.Sobal@meduniwien.ac.at; Menzel, Ernst Johannes [Institute of Immunology, Medical University of Vienna, Vienna (Austria); Sinzinger, Helmut [Department of Nuclear Medicine, Medical University of Vienna, A-1090 Vienna, Waehringer Guertel 18-20 (Austria)

    2008-04-15

    Chondroitin sulfate (CS) is an endogenous component of cartilage which could determine osteoarthritis after radiolabeling. Radiolabeling was performed by {sup 99m}TcO{sub 4}{sup -}/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 {sup 99m}TcCS could be a promising imaging agent of osteoarthritis due to simple radiolabeling and high stability.

  8. Optimised labeling, preclinical and initial clinical aspects of CCK-2 receptor-targeting with 3 radiolabeled peptides

    Energy Technology Data Exchange (ETDEWEB)

    Breeman, Wouter A.P. [Department of Nuclear Medicine, Erasmus MC Rotterdam' s 3015 CE Rotterdam (Netherlands)], E-mail: w.a.p.breeman@erasmusmc.nl; Froeberg, A.C.; Blois, E. de; Gameren, A. van; Melis, M.; Jong, M. de [Department of Nuclear Medicine, Erasmus MC Rotterdam' s 3015 CE Rotterdam (Netherlands); Maina, T.; Nock, B.A. [Molecular Radiopharmacy Section, I/R-RP, NCSR ' Demokritos' , Athens (Greece); Erion, J.L. [BioSynthema Inc., St. Louis, MO (United States); Maecke, H.R. [Radiological Chemistry, University Hospital Basel (Switzerland); Krenning, E.P. [Department of Nuclear Medicine, Erasmus MC Rotterdam' s 3015 CE Rotterdam (Netherlands); Department of Internal Medicine, Erasmus MC, Rotterdam (Netherlands)

    2008-11-15

    Medullary thyroid carcinoma (MTC) expresses CCK-2 receptors. {sup 111}In-labeled DOTA-DGlu-Ala-Tyr-Gly-Trp-Met-Asp-Phe-NH{sub 2} (DOTA-MG11), DOTA-DAsp-Tyr-Nle-Gly-Trp-Nle-Asp-Phe-NH{sub 2} (DOTA-CCK), and {sup 99m}Tc-labeled N{sub 4}-Gly-DGlu-(Glu){sub 5}-Ala-Tyr-Gly-Trp-Met-Asp-Phe-NH{sub 2} ({sup 99m}Tc-Demogastrin 2) are analogs developed for CCK-2 receptor-targeted scintigraphy. All 3 radiolabeled analogs were selected on the basis of their high CCK-2 receptor affinity and their good in vitro serum stability, with in vitro serum t{sub 1/2} values of several hours. Radiolabeling of DOTA-peptides with {sup 111}In requires a heating procedure, typically in the range of 80 deg. - 100 deg. C up to 30 min. Following this procedure with DOTA-MG11 resulted in a >98 % incorporation of {sup 111}In, however, with a radiochemical purity (RCP) of <50 %. The decrease in RCP was found to be due to oxidation of the methionine residue in the molecule. Moreover, this oxidized compound lost its CCK-2 receptor affinity. Therefore, conditions during radiolabeling were optimised: labeling of DOTA-MG11 and DOTA-CCK with {sup 111}In involved 5 min heating at 80 deg. C and led to an incorporation of {sup 111}In of >98 %. In addition, all analogs were radiolabeled in the presence of quenchers to prevent radiolysis and oxidation resulting in a RCP of >90 %. All 3 radiolabeled analogs were i.v. administered to 6 MTC patients: radioactivity cleared rapidly by the kidneys, with no significant differences in the excretion pattern of the 3 radiotracers. All 3 radiolabeled analogs exhibited a low in vivo stability in patients, as revealed during analysis of blood samples, with the respective t{sub 1/2} found in the order of minutes. In patient blood, the rank of radiopeptide in vivo stability was: {sup 99m}Tc-Demogastrin 2 (t{sub 1/2} 10-15 min)>{sup 111}In-DOTA-CCK (t{sub 1/2}{approx}5-10 min)>{sup 111}In-DOTA-MG11 (t{sub 1/2}<5 min)

  9. Remote-loading of liposomes with manganese-52 and in vivo evaluation of the stabilities of 52Mn-DOTA and 64Cu-DOTA using radiolabelled liposomes and PET imaging.

    Science.gov (United States)

    Jensen, Andreas I; Severin, Gregory W; Hansen, Anders E; Fliedner, Frederikke P; Eliasen, Rasmus; Parhamifar, Ladan; Kjær, Andreas; Andresen, Thomas L; Henriksen, Jonas R

    2018-01-10

    Liposomes are nanoparticles used in drug delivery that distribute over several days in humans and larger animals. Radiolabeling with long-lived positron emission tomography (PET) radionuclides, such as manganese-52 ( 52 Mn, T½=5.6days), allow the imaging of this biodistribution. We report optimized protocols for radiolabeling liposomes with 52 Mn, through both remote-loading and surface labeling. For comparison, liposomes were also remote-loaded and surface labeled with copper-64 ( 64 Cu, T½=12.7h) through conventional means. The chelator DOTA was used in all cases. The in vivo stability of radiometal chelates is widely debated but studies that mimic a realistic in vivo setting are lacking. Therefore, we employed these four radiolabeled liposome types as platforms to demonstrate a new concept for such in vivo evaluation, here of the chelates 52 Mn-DOTA and 64 Cu-DOTA. This was done by comparing "shielded" remote-loaded with "exposed" surface labeled variants in a CT26 tumor-bearing mouse model. Remote loading (90min at 55°C) and surface labeling (55°C for 2h) of 52 Mn gave excellent radiolabeling efficiencies of 97-100% and 98-100% respectively, and the liposome biodistribution was imaged by PET for up to 8days. Liposomes with surface-conjugated 52 Mn-DOTA exhibited a significantly shorter plasma half-life (T ½ =14.4h) when compared to the remote-loaded counterpart (T ½ =21.3h), whereas surface-conjugated 64 Cu-DOTA cleared only slightly faster and non-significantly, when compared to remote-loaded (17.2±2.9h versus 20.3±1.2h). From our data, we conclude the successful remote-loading of liposomes with 52 Mn, and furthermore that 52 Mn-DOTA may be unstable in vivo whereas 64 Cu-DOTA appears suitable for quantitative imaging. Copyright © 2017 Elsevier B.V. All rights reserved.

  10. Authentically radiolabelled Mn(II) complexes as bimodal PET/MR tracers

    Energy Technology Data Exchange (ETDEWEB)

    Vanasschen, Christian; Brandt, Marie; Ermert, Johannes [Institute of Neuroscience and Medicine, INM-5 - Nuclear Chemistry, Forschungszentrum Jülich (Germany); Neumaier, Bernd [Institute for Radiochemistry and Experimental Molecular Imaging, Medical Clinics, University of Cologne (Germany); Coenen, Heinz H [Institute of Neuroscience and Medicine, INM-5 - Nuclear Chemistry, Forschungszentrum Jülich (Germany)

    2015-05-18

    The development of small molecule bimodal PET/MR tracers is mainly hampered by the lack of dedicated preparation methods. Authentic radiolabelling of MR contrast agents ensures easy access to such probes: a ligand, chelating a paramagnetic metal ion (e.g. Mn2+) and the corresponding PET isotope (e.g. 52gMn), leads to a “cocktail mixture” where both imaging reporters exhibit the same pharmacokinetics. Paramagnetic [55Mn(CDTA)]2- shows an excellent compromise between thermodynamic stability, kinetic inertness and MR contrast enhancement. Therefore, the aim of this study was to develop new PET/MR tracers by labelling CDTA ligands with paramagnetic manganese and the β+-emitter 52gMn. N.c.a. 52gMn (t1/2: 5.6 d; Eβ+: 575.8 keV (29.6%)) was produced by proton irradiation of a natCr target followed by cation-exchange chromatography. CDTA was radiolabelled with n.c.a. 52gMn2+ in NaOAc buffer (pH 6) at RT. The complex was purified by RP-HPLC and its stability tested in PBS and blood plasma at 37°C. The redox stability was assessed by monitoring the T1 relaxation (20 MHz) in HEPES buffer (pH 7.4). A functionalized CDTA ligand was synthesized in 5 steps. [52gMn(CDTA)]2- was quantitatively formed within 30 min at RT. The complex was stable for at least 6 days in PBS and blood plasma at 37°C and no oxidation occurred within 7 months storage at RT. Labelling CDTA with an isotopic 52g/55Mn2+ mixture led to the corresponding bimodal PET/MR tracer. Furthermore, a functionalized CDTA ligand was synthesized with an overall yield of 18-25%. [52g/55Mn(CDTA)]2-, the first manganese-based bimodal PET/MR tracer prepared, exhibits excellent stability towards decomplexation and oxidation. This makes the functionalized CDTA ligand highly suitable for designing PET/MR tracers with high relaxivity or targeting properties.

  11. Authentically radiolabelled Mn(II) complexes as bimodal PET/MR tracers

    International Nuclear Information System (INIS)

    Vanasschen, Christian; Brandt, Marie; Ermert, Johannes; Neumaier, Bernd; Coenen, Heinz H

    2015-01-01

    The development of small molecule bimodal PET/MR tracers is mainly hampered by the lack of dedicated preparation methods. Authentic radiolabelling of MR contrast agents ensures easy access to such probes: a ligand, chelating a paramagnetic metal ion (e.g. Mn2+) and the corresponding PET isotope (e.g. 52gMn), leads to a “cocktail mixture” where both imaging reporters exhibit the same pharmacokinetics. Paramagnetic [55Mn(CDTA)]2- shows an excellent compromise between thermodynamic stability, kinetic inertness and MR contrast enhancement. Therefore, the aim of this study was to develop new PET/MR tracers by labelling CDTA ligands with paramagnetic manganese and the β+-emitter 52gMn. N.c.a. 52gMn (t1/2: 5.6 d; Eβ+: 575.8 keV (29.6%)) was produced by proton irradiation of a natCr target followed by cation-exchange chromatography. CDTA was radiolabelled with n.c.a. 52gMn2+ in NaOAc buffer (pH 6) at RT. The complex was purified by RP-HPLC and its stability tested in PBS and blood plasma at 37°C. The redox stability was assessed by monitoring the T1 relaxation (20 MHz) in HEPES buffer (pH 7.4). A functionalized CDTA ligand was synthesized in 5 steps. [52gMn(CDTA)]2- was quantitatively formed within 30 min at RT. The complex was stable for at least 6 days in PBS and blood plasma at 37°C and no oxidation occurred within 7 months storage at RT. Labelling CDTA with an isotopic 52g/55Mn2+ mixture led to the corresponding bimodal PET/MR tracer. Furthermore, a functionalized CDTA ligand was synthesized with an overall yield of 18-25%. [52g/55Mn(CDTA)]2-, the first manganese-based bimodal PET/MR tracer prepared, exhibits excellent stability towards decomplexation and oxidation. This makes the functionalized CDTA ligand highly suitable for designing PET/MR tracers with high relaxivity or targeting properties.

  12. Improved tumor targeting of anti-HER2 nanobody through N-succinimidyl 4-guanidinomethyl-3-iodobenzoate radiolabeling.

    Science.gov (United States)

    Pruszynski, Marek; Koumarianou, Eftychia; Vaidyanathan, Ganesan; Revets, Hilde; Devoogdt, Nick; Lahoutte, Tony; Lyerly, H Kim; Zalutsky, Michael R

    2014-04-01

    Nanobodies are approximately 15-kDa proteins based on the smallest functional fragments of naturally occurring heavy chain-only antibodies and represent an attractive platform for the development of molecularly targeted agents for cancer diagnosis and therapy. Because the human epidermal growth factor receptor type 2 (HER2) is overexpressed in breast and ovarian carcinoma, as well as in other malignancies, HER2-specific Nanobodies may be valuable radiodiagnostics and therapeutics for these diseases. The aim of the present study was to evaluate the tumor-targeting potential of anti-HER2 5F7GGC Nanobody after radioiodination with the residualizing agent N-succinimidyl 4-guanidinomethyl 3-(125/131)I-iodobenzoate (*I-SGMIB). The 5F7GGC Nanobody was radiolabeled using *I-SGMIB and, for comparison, with N(ε)-(3-*I-iodobenzoyl)-Lys(5)-N(α)-maleimido-Gly(1)-GEEEK (*I-IB-Mal-d-GEEEK), another residualizing agent, and by direct radioiodination using IODO-GEN ((125)I-Nanobody). The 3 labeled Nanobodies were evaluated in affinity measurements, and paired-label internalization assays were performed on HER2-expressing BT474M1 breast carcinoma cells and in paired-label tissue distribution measurements in mice bearing subcutaneous BT474M1 xenografts. *I-SGMIB-Nanobody was produced in 50.4% ± 3.6% radiochemical yield and exhibited a dissociation constant of 1.5 ± 0.5 nM. Internalization assays demonstrated that intracellular retention of radioactivity was up to 1.5-fold higher for *I-SGMIB-Nanobody than for coincubated (125)I-Nanobody or *I-IB-Mal-d-GEEEK-Nanobody. Peak tumor uptake for *I-SGMIB-Nanobody was 24.50% ± 9.89% injected dose/g at 2 h, 2- to 4-fold higher than observed with other labeling methods, and was reduced by 90% with trastuzumab blocking, confirming the HER2 specificity of localization. Moreover, normal-organ clearance was fastest for *I-SGMIB-Nanobody, such that tumor-to-normal-organ ratios greater than 50:1 were reached by 24 h in all tissues except lungs

  13. Radiolabeling of NOTA and DOTA with Positron Emitting {sup 68}Ga and Investigation of In Vitro Properties

    Energy Technology Data Exchange (ETDEWEB)

    Jeong, Jae Min; Kim, Young Ju; Lee, Yun Sang; Lee, Dong Soo; Chung, June Key; Lee, Myung Chul [Seoul National University College of Medicine, Seoul (Korea, Republic of)

    2009-08-15

    We established radiolabeling conditions of NOTA and DOTA with a generator-produced PET radionuclide {sup 68}Ga and studied in vitro characteristics such as stability, serum protein binding, octanol/water distribution, and interference with other metal ions. Various concentrations of NOTA{center_dot}3HCl and DOTA{center_dot}4HCl were labeled with 1 mL {sup 68}GaCl{sub 3} (0.18{approx}5.75 mCi in 0.1 M HCl) in various pH. NOTA{center_dot}3HCl (0.373 mM) was labeled with {sup 68}GaCl{sub 3} (0.183{approx}0.232 mCi/0.1 M HCl 1.0 mL) in the presence of CuCl{sub 2}, FeCl{sub 2}, InCl{sub 3}, FeCl{sub 3}, GaCl{sub 3}, MgCl{sub 2} or CaCl{sub 2} (0{approx}6.07 mM) at room temperature. The labeling efficiencies of {sup 68}Ga-NOTA and {sup 68}Ga-DOTA were checked by ITLC-SG using acetone or saline as mobile phase. Stabilities, protein bindings, and octanol distribution coefficients of the labeled compounds also were investigated. {sup 68}Ga-NOTA and {sup 68}Ga-DOTA were labeled optimally at pH 6.5 and pH 3.5, respectively, and the chelates were stable for 4 hr either in the reaction mixture at room temperature or in the human serum at 37 .deg. C. NOTA was labeled at room temperature while DOTA required heating for labeling. {sup 68}Ga-NOTA labeling efficiency was reduced by CuCl{sub 2}, FeCl{sub 2}, InCl{sub 2}, FeCl{sub 3} or GaCl{sub 3}, however, was not influenced by MgCl{sub 2} or CaCl{sub 2}. The protein binding was low (2.04{approx}3.32%). Log P value of {sup 68}Ga-NOTA was -3.07 indicating high hydrophilicity. We found that NOTA is a better bifunctional chelating agent than DOTA for {sup 68}Ga labeling. Although, {sup 68}Ga-NOTA labeling is interfered by various metal ions, it shows high stability and low serum protein binding.

  14. A perspective on plant origin radiolabeled compounds, their biological affinities and interaction between plant extracts with radiopharmaceuticals

    International Nuclear Information System (INIS)

    Zumrut Biber Muftuler, F.; Ayfer Yurt Kilcar; Perihan Unak

    2015-01-01

    Plant origin products having anticancer properties come into prominence due to widespread of cancer. There is significant increase on the usage of plant origin products and their purification to investigate the potential use at the treatment and diagnosis. Plant origin radiolabeled compounds have been attracting more scientific attention since the achievement of earlier researches. Furthermore, plant extracts are consumed quite a lot with unknown side effects of their contents. Researchers focus on investigation of their interactions with radiopharmaceuticals. Current review is carried out to evaluate the contribution of plant extracts for the development of new plant origin radiolabeled ( 125 / 131 I, 99m Tc) compounds for imaging and/or therapy and to investigate the interaction of plant extracts with radiopharmaceuticals. (author)

  15. Radiolabeling of equine platelets in plasma with 111In-(2-mercaptopyridine-N-oxide) and their in vivo survival

    International Nuclear Information System (INIS)

    Coyne, C.P.; Kelly, A.B.; Hornof, W.J.; O'Brien, T.R.; Philp, M.S.; Lamb, J.F.

    1987-01-01

    A method is presented for the in vitro isolation and radiolabeling of equine platelets with the isotope indium 111 ( 111 In: half-life = 2.8 days, gamma = 173 keV, 89%; 247 keV, 94%). The technique described involves complexing 111 In with the lipid-soluble chelating agent, 2-mercaptopyridine-N-oxide (merc), in an aqueous medium. 111 In-merc platelet-labeling efficiencies in autologous plasma pretreated with or without ferric citrate reagent were 82 +/- 7% and 24 +/- 12%, respectively. Mean intravascular survivals of 111 In-merc-radiolabeled platelets in 8 healthy horses according to simple linear, exponential, mean, weighted-mean residual sum of squares analysis, and multiple-hit model were 5.5 +/- 0.49, 3.5 +/- 0.53, 4.5 +/- 0.18, 4.3 +/- 0.65, and 3.6 +/- 0.97 days, respectively

  16. Comparison of radiolabeling efficiency of peptides containing the RGD domain using the Tc-99M and I-131 radioisotopes

    International Nuclear Information System (INIS)

    Sobral, Danielle V.; Cabral, Francisco Romero; Malavolta, Luciana

    2017-01-01

    Full text: Introduction: Radiolabeled peptides have become very important in nuclear medicine and oncology in recent years mainly because they represent the molecular basis for in vivo imaging and radiopharmaceutical therapy with high specificity and affinity for over expressed receptors in tumors (Thno 2(5):481-501, 2012 / Drug Discov. Today. 7:1224-1232, 2012). In this context, peptides containing the RGD domain which possess high affinity for the αvβ3 integrin receptor have become an important tool in a wide variety tumor, including glioblastoma (Exp. Opin. Drug Deliv. 8:1041- 1056, 2011). Objective: The goal of this work was to compare the radiolabeling efficiency of the GRGDYV and GRGDHV peptides when radiolabeled with the 131 I and 99m Tc radioisotopes, respectively, as well as, to evaluate the features of synthesized complexes. Methods: The GRGDYV and GRGDHV fragments were manually synthesized by peptide synthesis in solid phase accordingly to the Fmoc protocol and purified by preparative HPLC. The GRGDYV and GRGDHV peptides were radiolabeled with the I-131 and Tc-99m radioisotopes respectively, through of the direct method of radiolabeling. The radioiodination was evaluated and optimized using the methodology of Chloramine-T and for the peptide containing the histidine aminoacid the tricarbonyl method was used. Radiochemical yield analyses of [ 131 I]-GRGDYV and [ 99m Tc]-GRGDHV peptides were performed by thin layer chromatography on silica gel TLC-SG (Al) in ACN 95%. The radiolabeled peptides were purified by using solid phase extraction (Sep-Pak C18 filter). The stability studies were realized at 2, 24, 48 and 72 hours in room temperature and refrigerate (4 deg C) for [ 131 I]-GRGDYV and up to 6 hours for the fragment [ 99m Tc]-GRGDHV. Partition coefficient was determinate for both radiopeptides. Results: The peptides [ 131 I]-GRGDYV and [ 99m Tc]-GRGDHV were efficiently synthesized, radiolabeled and showed radiochemical yield of 91.02% ± 1.68 (n=5

  17. Comparison of radiolabeling efficiency of peptides containing the RGD domain using the Tc-99M and I-131 radioisotopes

    Energy Technology Data Exchange (ETDEWEB)

    Sobral, Danielle V.; Cabral, Francisco Romero; Malavolta, Luciana [Santa Casa de São Paulo, SP (Brazil). Faculdade de Ciências Médicas; Durante, Ana C. Ranucci; Miranda, Ana C. Camargo; Barbosa, Marycel R. F.Figols de [Instituto Israelita de Ensino e Pesquisa Albert Einstein, São Paulo, SP (Brazil)

    2017-07-01

    Full text: Introduction: Radiolabeled peptides have become very important in nuclear medicine and oncology in recent years mainly because they represent the molecular basis for in vivo imaging and radiopharmaceutical therapy with high specificity and affinity for over expressed receptors in tumors (Thno 2(5):481-501, 2012 / Drug Discov. Today. 7:1224-1232, 2012). In this context, peptides containing the RGD domain which possess high affinity for the αvβ3 integrin receptor have become an important tool in a wide variety tumor, including glioblastoma (Exp. Opin. Drug Deliv. 8:1041- 1056, 2011). Objective: The goal of this work was to compare the radiolabeling efficiency of the GRGDYV and GRGDHV peptides when radiolabeled with the {sup 131}I and {sup 99m}Tc radioisotopes, respectively, as well as, to evaluate the features of synthesized complexes. Methods: The GRGDYV and GRGDHV fragments were manually synthesized by peptide synthesis in solid phase accordingly to the Fmoc protocol and purified by preparative HPLC. The GRGDYV and GRGDHV peptides were radiolabeled with the I-131 and Tc-99m radioisotopes respectively, through of the direct method of radiolabeling. The radioiodination was evaluated and optimized using the methodology of Chloramine-T and for the peptide containing the histidine aminoacid the tricarbonyl method was used. Radiochemical yield analyses of [{sup 131}I]-GRGDYV and [{sup 99m}Tc]-GRGDHV peptides were performed by thin layer chromatography on silica gel TLC-SG (Al) in ACN 95%. The radiolabeled peptides were purified by using solid phase extraction (Sep-Pak C18 filter). The stability studies were realized at 2, 24, 48 and 72 hours in room temperature and refrigerate (4 deg C) for [{sup 131}I]-GRGDYV and up to 6 hours for the fragment [{sup 99m}Tc]-GRGDHV. Partition coefficient was determinate for both radiopeptides. Results: The peptides [{sup 131}I]-GRGDYV and [{sup 99m}Tc]-GRGDHV were efficiently synthesized, radiolabeled and showed

  18. A Fluorine-18 Radiolabeling Method Enabled by Rhenium(I) Complexation Circumvents the Requirement of Anhydrous Conditions.

    Science.gov (United States)

    Klenner, Mitchell A; Pascali, Giancarlo; Zhang, Bo; Sia, Tiffany R; Spare, Lawson K; Krause-Heuer, Anwen M; Aldrich-Wright, Janice R; Greguric, Ivan; Guastella, Adam J; Massi, Massimiliano; Fraser, Benjamin H

    2017-05-11

    Azeotropic distillation is typically required to achieve fluorine-18 radiolabeling during the production of positron emission tomography (PET) imaging agents. However, this time-consuming process also limits fluorine-18 incorporation, due to radioactive decay of the isotope and its adsorption to the drying vessel. In addressing these limitations, the fluorine-18 radiolabeling of one model rhenium(I) complex is reported here, which is significantly improved under conditions that do not require azeotropic drying. This work could open a route towards the investigation of a simplified metal-mediated late-stage radiofluorination method, which would expand upon the accessibility of new PET and PET-optical probes. © 2017 Wiley-VCH Verlag GmbH & Co. KGaA, Weinheim.

  19. Synthesis of radio-labeled caffeyl alcohol- and 5-hydroxyconiferyl alcohol-4-O-β-D-glucosides

    International Nuclear Information System (INIS)

    Matsui, Naoyuki; Fukushima, Kazuhiko; Terashima, Noritsugu; Yasuda, Seiichi

    1996-01-01

    Syntheses of caffeyl alcohol-4-O-β-D-glucoside and 5-hydroxyconiferyl alcohol-4-O-β-D-glucoside were achieved with radio-labeling with 14 C at the glucose residue and with 3 H at the side chain γ-position of aglycon. The treatment of these compounds with commercially available β-glucosidase gave the corresponding aglycons, caffeyl alcohol, and 5-hydroxyconiferyl alcohol. (author)

  20. Elucidating the role of dissolution in CeO{sub 2} nanoparticle plant uptake by smart radiolabeling

    Energy Technology Data Exchange (ETDEWEB)

    Schymura, Stefan; Hildebrand, Heike; Franke, Karsten [Institute of Resource Ecology, Helmholtz-Zentrum Dresden-Rossendorf, Leipzig (Germany); Fricke, Thomas [Vita34 AG, Business Unit BioPlanta, Leipzig (Germany); University of Bonn, Institute of Crop Science and Resource Conservation, Division Plant Nutrition (Germany)

    2017-06-19

    The identification of major uptake pathways in plants is an important factor when evaluating 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 in contrast to a possible uptake in the form of ionic cerium. (copyright 2017 Wiley-VCH Verlag GmbH and Co. KGaA, Weinheim)

  1. Rapid, radiolabeled-microculture method that uses macrophages for in vitro evaluation of Mycobacterium leprae viability and drug susceptibility.

    Science.gov (United States)

    Mittal, A; Sathish, M; Seshadri, P S; Nath, I

    1983-04-01

    This paper describes a microculture rapid assay using radiolabeling and mouse macrophages to determine the viability and the drug susceptibility or resistance of Mycobacterium leprae. Comparison of M. leprae resident macrophage cultures maintained in 96-well flat-bottomed plates showed results for viability and susceptibility or resistance to dapsone that were similar to results for concurrent cultures in Leighton tubes with greater numbers of bacilli and macrophages.

  2. Rapid, Radiolabeled-Microculture Method That Uses Macrophages for In Vitro Evaluation of Mycobacterium leprae Viability and Drug Susceptibility

    OpenAIRE

    Mittal, A.; Sathish, M.; Seshadri, P. S.; Nath, Indira

    1983-01-01

    This paper describes a microculture rapid assay using radiolabeling and mouse macrophages to determine the viability and the drug susceptibility or resistance of Mycobacterium leprae. Comparison of M. leprae resident macrophage cultures maintained in 96-well flat-bottomed plates showed results for viability and susceptibility or resistance to dapsone that were similar to results for concurrent cultures in Leighton tubes with greater numbers of bacilli and macrophages.

  3. Platelet crossmatch tests using radiolabelled staphylococcal protein A or peroxidase anti-peroxidase in alloimmunised patients

    International Nuclear Information System (INIS)

    Yam, P.; Petz, L.D.; Scott, E.P.; Santos, S.

    1984-01-01

    Refractoriness to random-donor platelets as a result of alloimmunization remains a major problem in long-term platelet transfusion therapy despite the use of HLA-matched platelets. A study has been made of two methods for detection of platelet associated IgG as platelet crossmatch tests for the selection of platelet donors. These methods use radiolabelled staphylococcal protein A( 125 I-SPA) and peroxidase anti-peroxidase (PAP), respectively. One hundred and ten crossmatch tests using 125 I-SPA were performed retrospectively in 18 alloimmunized patients. The results indicated that the predictive value of a positive or a negative test was 87%; the sensitivity was 73% and the specificity was 95%. Results with the PAP test were similar. The HLA types were known for 48 donor-recipient pairs. With few exceptions, there was a correlation between the results of the platelet crossmatch tests and the effectiveness of platelet transfusion regardless of the degree of HLA match. These results indicate that platelet crossmatch tests may be valuable even when closely HLA matched donors are not available. A large-scale prospective study is warranted, particularly in highly immunized patients. (author)

  4. Radiolabeling of mammalian spermatozoa and their use to monitor sperm transport in females

    International Nuclear Information System (INIS)

    Lorton, S.P.; Gatley, S.J.; Lieberman, L.M.; First, N.L.

    1980-01-01

    Radiolabeling of mammalian spermatozoa with 131 I, 67 Ga, 111 In, and /sup 99m/Tc was investigated. Spermatozoa were labeled with /sup 99m/Tc for in vivo studies because of a high labeling yield (70 to 90%) combined with the lack of impairment of sperm motility. Ovariectomized sheep were brought into estrus by sequential administration of progesterone and estradiol cyprionate. Sheep were necropsied up to 6 hours after insemination with /sup 99m/Tc-labeled ram sperm and their reproductive tracts were resected and examined with a rectilinear scanner. Radioactivity was clearly observed in the fallopian tubes, with larger amounts in the vaginas, cervices, and uteri. In contrast, when /sup 99m/Tc-spermatozoa were replaced with /sup 99m/TcO 4 - , much less radioactivity remained in the reproductive tract at resection and this was evenly distributed. Some label left the /sup 99m/Tc-spermatozoa in vivo, but radioactivity remained on the cells long enough to consider attempting to monitor sperm transport in vivo in a suitable species

  5. Variability of gastric emptying measurements in man employing standardized radiolabeled meals

    International Nuclear Information System (INIS)

    Brophy, C.M.; Moore, J.G.; Christian, P.E.; Egger, M.J.; Taylor, A.T.

    1986-01-01

    Radiolabeled liquid and solid portions of standardized 300-g meals were administered on four different study days to eight healthy subjects in an attempt to define the range of inter- and intrasubject variability in gastric emptying. Meal half emptying times, analysis of variance, and intraclass correlations were computed and compared within and between subjects. The mean solid half emptying time was 58 +/- 17 min (range 29-92), while the mean liquid half emptying time was 24 +/- 8 min (range 12-37). A nested random effects analysis of variance showed moderate intrasubject variability for solid emptying and high intrasubject variability for liquid emptying. The variability of solid and liquid emptying was comparable and relatively large when compared with other reports in the literature. The isotopic method for measuring gastric emptying is a valuable tool for investigating problems in gastric pathophysiology, particularly when differences between groups of subjects are sought. However, meal emptying time is a variable phenomenon in healthy subjects with significant inter- and intraindividual day-to-day differences. These day-to-day variations in gastric emptying must be considered in interpreting individual study results

  6. Radiolabelling and PET brain imaging of the α1-adrenoceptor antagonist Lu AE43936

    International Nuclear Information System (INIS)

    Risgaard, Rune; Ettrup, Anders; Balle, Thomas; Dyssegaard, Agnete; Hansen, Hanne Demant; Lehel, Szabolcs; Madsen, Jacob; Pedersen, Henrik; Püschl, Ask; Badolo, Lassina; Bang-Andersen, Benny; Knudsen, Gitte Moos; Kristensen, Jesper Langgaard

    2013-01-01

    Cerebral α 1 -adrenoceptors are a common target for many antipsychotic drugs. Thus, access to positron emission tomography (PET) brain imaging of α 1 -adrenoceptors could make important contributions to the understanding of psychotic disorders as well as to the pharmacokinetics and occupancy of drugs targeting the α 1 -adrenoceptors. However, so far no suitable PET radioligand has been developed for brain imaging of α 1 -adrenoceptors. Here, we report the synthesis of both enantiomers of the desmethyl precursors of the high affinity α 1 -adrenoceptor ligand Lu AE43936 (). The two enantiomers of were subsequently [ 11 C] radiolabelled and evaluated for brain uptake and binding by PET imaging in Danish Landrace pigs. (S)-[ 11 C]- and (R)-[ 11 C]- showed very limited brain uptake. Pre-treatment with cyclosporine A (CsA) resulted in a large increase in brain uptake, indicating that (R)-[ 11 C]- is a substrate for active efflux-transporters. This was confirmed in Madin Darby canine kidney (MDCK) cells overexpressing permeability glycoprotein (Pgp). In conclusion, the limited brain uptake of both (S)-[ 11 C]- and (R)-[ 11 C]- in the pig brain necessitates the search for alternative radioligands for in vivo PET brain imaging of α 1 -adrenoceptors.

  7. 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

  8. Characterization of the association of radiolabeled bleomycin A2 with HeLa cells

    International Nuclear Information System (INIS)

    Roy, S.N.; Horwitz, S.B.

    1984-01-01

    The association of [ 3 H]bleomycin A2 and Cu(II):[ 3 H]bleomycin A2 with HeLa cells has been characterized. Under the conditions of our experiments, approximately 0.1% of the total drug in the medium associates with HeLa cells. Both forms of the drug bind to HeLa cells in a specific and saturable manner, with a Km of 20 microM and a Vmax of 2.5 pmol/min/10(6) cells. Scatchard analysis of the specific binding data demonstrates a single set of high-affinity binding sites. Cytotoxic activities of both forms of the drug are similar, with a 50% lethal dose of 0.5 microM at 48 hr. The specific binding in HeLa cells of either the labeled metal-free drug or its copper complex is reversible by a 100-fold excess of either unlabeled drug. Interaction of the drug with cells is temperature sensitive but is unaffected by metabolic poisons, suggesting that this process is not energy dependent. Isolation of DNA from HeLa cells incubated with the drug indicates that 1 mol of either [ 3 H]bleomycin A2 or Cu(II):[ 3 H]bleomycin A2 binds per 10(8) nucleotides. Further studies with the radiolabeled drug are required to define precisely the mechanisms involved in bleomycin uptake and compartmentalization within the cell

  9. A simple method for enzymatic synthesis of unlabeled and radiolabeled Hydroxycinnamate-CoA

    Energy Technology Data Exchange (ETDEWEB)

    Rautergarten, Carsten; Baidoo, Edward; Keasling, Jay; Vibe Scheller, Henrik

    2011-07-20

    Hydroxycinnamate coenzyme A (CoA) thioesters are substrates for biosynthesis of lignin and hydroxycinna- mate esters of polysaccharides and other polymers. Hence, a supply of these substrates is essential for investigation of cell wall biosynthesis. In this study, three recombinant enzymes, caffeic acid 3-O-methyltransferase, 4-coumarate- CoA ligase 1, and 4-coumarate-CoA ligase 5, were cloned from wheat, tobacco, and Arabidopsis, respectively, and were used to synthesize {sup 14}C-feruloyl-CoA, caffeoyl-CoA, p-coumaroyl-CoA, feruloyl-CoA, and sinapoyl-CoA. The corresponding hydroxycinnamoyl-CoA thioesters were high-performance liquid chromatography purified, the only extraction/purification step necessary, with total yields between 88-95%. Radiolabeled {sup 14}C-feruloyl-CoA was generated from caffeic acid and S-adenosyl-{sup 14}C-methionine under the combined action of caffeic acid 3-O-methyltransferase and 4-coumarate-CoA ligase 1. About 70% of {sup 14}C-methyl groups from S-adenosyl methionine were incorporated into the final product. The methods presented are simple, fast, and efficient for the preparation of the hydroxycinnamate thioesters.

  10. SPECT/CT with radiolabeled somatostatin analogues in the evaluation of systemic granulomatous infections.

    Science.gov (United States)

    Monteiro, Paulo Henrique Silva; de Souza, Thiago Ferreira; Moretti, Maria Luiza; Resende, Mariangela Ribeiro; Mengatti, Jair; de Lima, Mariana da Cunha Lopes; Santos, Allan Oliveira; Ramos, Celso Darío

    2017-01-01

    To evaluate SPECT/CT with radiolabeled somatostatin analogues (RSAs) in systemic granulomatous infections in comparison with gallium-67 ( 67 Ga) citrate scintigraphy. We studied 28 patients with active systemic granulomatous infections, including tuberculosis, paracoccidioidomycosis, pneumocystosis, cryptococcosis, aspergillosis, leishmaniasis, infectious vasculitis, and an unspecified opportunistic infection. Of the 28 patients, 23 had started specific treatment before the study outset. All patients underwent whole-body SPECT/CT imaging: 7 after injection of 99m Tc-EDDA-HYNIC-TOC, and 21 after injection of 111 In-DTPA-octreotide. All patients also underwent 67 Ga citrate imaging, except for one patient who died before the 67 Ga was available. In 20 of the 27 patients who underwent imaging with both tracers, 27 sites of active disease were detected by 67 Ga citrate imaging and by SPECT/CT with an RSA. Both tracers had negative results in the other 7 patients. RSA uptake was visually lower than 67 Ga uptake in 11 of the 20 patients with positive images and similar to 67 Ga uptake in the other 9 patients. The only patient who did not undergo 67 Ga scintigraphy underwent 99m Tc-EDDA-HYNIC-TOC SPECT/CT-guided biopsy of a lung cavity with focal RSA uptake, which turned to be positive for aspergillosis. SPECT/CT with 99m Tc-EDDA-HYNIC-TOC or 111 In-DTPA-octreotide seems to be a good alternative to 67 Ga citrate imaging for the evaluation of patients with systemic granulomatous disease.

  11. Synthesis of radiolabelled organic compounds for use as water tracers in oil reservoirs

    International Nuclear Information System (INIS)

    Eriksen, D.Oe.; Bjoernstad, V.

    1999-01-01

    Injection of water into oil containing strata to maintain field pressure and to replace oil is usually the primary choice to enhance oil-recovery. Use of tracer methods is becoming an important part of the oil companies' basis for making economical decisions. Such water tracing requires passive tracers, i.e. compounds that behave exactly like the substance studied under the conditions of interest. This implies that a water-tracer in a water-flooded oil-field must fulfil requirements like no absorption to reservoir rock, no partitioning (or distribution) with respect to the other fluids present, long time thermal stability, microbial resistance and high detectability. In addition, the tracer compound has to be environmentally acceptable and available at a reasonable cost. Among the extensive number of compounds tested according to these criteria in the laboratory we have qualified four compounds as tracers for water in oil reservoirs. For three of them we propose radiolabelling syntheses with 14 C as radioactive label to lower detection limits. The compounds are benzene 1,2- and 1,3-dicarboxylic acids and benzene 1,3,5-tricarboxylic acid. (author)

  12. Foliar leaching, translocation, and biogenic emission of 35S in radiolabeled loblolly pines

    International Nuclear Information System (INIS)

    Garten, C.T. Jr.

    1990-01-01

    Foliar leaching, basipetal (downward) translocation, and biogenic emission of sulfur (S), as traced by 35 S, were examined in a field study of loblolly pines. Four trees were radiolabeled by injection with amounts of 35 S in the 6-8 MBq range, and concentrations in needle fall, stemflow, throughfall, and aboveground biomass were measured over a period of 15-20 wk after injection. The contribution of dry deposition to sulfate-sulfur (SO 4 2- -S) concentrations in net throughfall (throughfall SO 4 2- -S concentration minus that in incident precipitation) beneath all four trees was > 90%. Calculations indicated that about half of the summertime SO 2 dry deposition flux to the loblolly pines was fixed in the canopy and not subsequently leached by rainfall. Based on mass balance calculations, 35 S losses through biogenic emissions from girdled trees were inferred to be 25-28% of the amount injected. Estimates based on chamber methods and mass balance calculations indicated a range in daily biogenic S emission of 0.1-10 μg/g dry needles. Translocation of 35 S to roots in nongirdled trees was estimated to be between 14 and 25% of the injection. It is hypothesized that biogenic emission and basipetal translocation of S (and not foliar leaching) are important mechanisms by which forest trees physiologically adapt to excess S in the environment

  13. 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.)

  14. 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.

  15. Incorporation of radiolabeled whey proteins into casein micelles by heat processing

    International Nuclear Information System (INIS)

    Noh, B.; Richardson, T.

    1989-01-01

    Skim milk was heated at .70, 95, and 140 degree C to simulate the processes of pasteurization, forewarming, and UHT sterilization, and the specific interactions between α-lactalbumin or β-lactoglobulin and the caseins studied using tracer amounts of added 14 C-labeled whey protein. Radioactivities of the whey and of the washed casein pellets from renneted skim milk were measured and the extent of the interaction estimated. Upon heating skim milk at 70 degree C for 45 s, less than 2% β-lactoglobulin and less than .3% α-lactalbumin were incorporated into the curd. Heating at 95 degree C for .5 to 20 min resulted in 58 to 85% of the β-lactoglobulin and 8 to 55% of the α-lactalbumin becoming associated with the curd. Heating at 140 degree C for 2 and 4 s caused 43 and 54% of the β-lactoglobulin and 9 and 12% of the α-lactalbumin, respectively, to be bound to the curd fraction. The radiolabeling technique is very sensitive and useful for tracing low levels of interaction between whey proteins and casein in heated milk systems

  16. Free thyroxin by radioimmunoassay: evaluation of a new direct method involving a radiolabeled thyroxin analog

    International Nuclear Information System (INIS)

    Kubasik, N.P.; Lundberg, P.A.; Brodows, R.G.; Hallauer, G.D.; Same, D.G.; Lindstedt, G.; Bengtsson, C.; Nystroem, E.

    1983-01-01

    The first performance evaluation of a new direct method for free thyroxin (T4) in serum by radioimmunoassay, with use of coated tubes and a radioiodinated T4 analog (Diagnostic Products Corp.) is presented. The assay is precise and robust: within-run imprecision (CV), 3.1-6.6%; between-run imprecision, 4.0-7.9%; no demonstrable variation between technologists irrespective of experience with the method. No outliers were observed when we compared the free T4 results with serum total T4. Reference values are reported for a total of 1243 euthyroid subjects; there was no significant age effect on serum free T4 in women 26 to 72 years old. The biological variation was about +/- 35% of the mean (2 SD). Free T4 results are the same for serum and plasma. The assay performs well in hypothyroidism and hyperthyroidism, and distinguishes individuals with thyroid disease from normal individuals. Free T4 values in women taking oral contraceptives are normal. Depressed results were often observed in acute nonthyroidal illness and continuing pregnancy. These results were directly comparable with those of another commercial direct radiolabeled-T4 analog kit for free T4

  17. Clearance and binding of radiolabeled glycoproteins by cells of the murine mononuclear phagocyte system

    International Nuclear Information System (INIS)

    Imber, M.J.

    1982-01-01

    The clearance and binding of radiolabeled lactoferrin and fast α 2 -macroglobulin were studied. Both glycoproteins cleared rapidly following intravenous injection in mice, and both bound specifically to discrete receptors on murine peritoneal macrophages. The simultaneous presence of excess, unlabeled ligands specific for receptors recognizing terminal fucose, mannose, N-acetylglucosamine or galactose residues did not inhibit the clearance or binding of either lactoferrin or fast-α 2 M. The clearance and binding of enzymatically defucosylated lactoferrin was indistinguishable from native lactoferrin, indicating that terminal α(1-3)-linked fucose on lactoferrin is not necessary for receptor recognition. The clearance and binding of two fast -α 2 M forms, α 2 M-trypsin and α 2 M-MeNH 2 cross compete with each other. Saturation binding studies indicated that the total binding of mannosyl -BSA, fusocyl-BSA, and N-acetylglucosaminyl-BSA to macrophages activated by BCG was approximately 15% of the levels observed with inflammatory macrophages elicited by thioglycollate broth. Cross-competition binding studies demonstrated a common surface receptor mediated binding of all three neoglycoprotein ligands and was identical to the receptor on mononuclear phagocytes that binds mannosyl- and N-acetylglucosaminyl-terminated glycoproteins. These results suggest that difference between discrete states of macrophage function may be correlated with selective changes in levels of the surface receptor for mannose-containing glycoproteins

  18. Radiolabelled molecules for imaging the translocator protein (18 kDa) using positron emission tomography

    International Nuclear Information System (INIS)

    Dolle, F.; Luus, C.; Reynolds, A.; Kassiou, M.

    2009-01-01

    The translocator protein (18 kDa) (TSPO), formerly known as the peripheral benzodiazepine receptor (PBR), was originally identified as an alternate binding site for the central benzodiazepine receptor (CBR) ligand, diazepam, in the periphery, but has now been distinguished as a novel site. The TSPO is ubiquitously expressed in peripheral tissues but only minimally in the healthy brain and increased levels of TSPO expression have been noted in neuro inflammatory conditions such as Alzheimer's disease, Parkinson's disease and stroke. This increase in TSPO expression has been reported to coincide with the process of micro-glial activation, whereby the brain's intrinsic immune system becomes active. Therefore, by using recently developed high affinity, selective TSPO ligands in conjunction with functional imaging modalities such as positron emission tomography (PET), it becomes possible to study the process of micro-glial activation in the living brain. A number of high affinity ligands, the majority of which are C, N-substituted acetamide derivatives, have been successfully radiolabelled and used in in vivo studies of the TSPO and the process of micro-glial activation. This review highlights recent achievements (up to December 2008) in the field of functional imaging of the TSPO as well as the radio-syntheses involved in such studies. (authors)

  19. Heat-induced-radiolabeling and click chemistry: A powerful combination for generating multifunctional nanomaterials.

    Directory of Open Access Journals (Sweden)

    Hushan Yuan

    Full Text Available A key advantage of nanomaterials for biomedical applications is their ability to feature multiple small reporter groups (multimodality, or combinations of reporter groups and therapeutic agents (multifunctionality, while being targeted to cell surface receptors. Here a facile combination of techniques for the syntheses of multimodal, targeted nanoparticles (NPs is presented, whereby heat-induced-radiolabeling (HIR labels NPs with radiometals and so-called click chemistry is used to attach bioactive groups to the NP surface. Click-reactive alkyne or azide groups were first attached to the nonradioactive clinical Feraheme (FH NPs. Resulting "Alkyne-FH" and "Azide-FH" intermediates, like the parent NP, tolerated 89Zr labeling by the HIR method previously described. Subsequently, biomolecules were quickly conjugated to the radioactive NPs by either copper-catalyzed or copper-free click reactions with high efficiency. Synthesis of the Alkyne-FH or Azide-FH intermediates, followed by HIR and then by click reactions for biomolecule attachment, provides a simple and potentially general path for the synthesis of multimodal, multifunctional, and targeted NPs for biomedical applications.

  20. Variability of gastric emptying measurements in man employing standardized radiolabeled meals

    Energy Technology Data Exchange (ETDEWEB)

    Brophy, C.M.; Moore, J.G.; Christian, P.E.; Egger, M.J.; Taylor, A.T.

    1986-08-01

    Radiolabeled liquid and solid portions of standardized 300-g meals were administered on four different study days to eight healthy subjects in an attempt to define the range of inter- and intrasubject variability in gastric emptying. Meal half emptying times, analysis of variance, and intraclass correlations were computed and compared within and between subjects. The mean solid half emptying time was 58 +/- 17 min (range 29-92), while the mean liquid half emptying time was 24 +/- 8 min (range 12-37). A nested random effects analysis of variance showed moderate intrasubject variability for solid emptying and high intrasubject variability for liquid emptying. The variability of solid and liquid emptying was comparable and relatively large when compared with other reports in the literature. The isotopic method for measuring gastric emptying is a valuable tool for investigating problems in gastric pathophysiology, particularly when differences between groups of subjects are sought. However, meal emptying time is a variable phenomenon in healthy subjects with significant inter- and intraindividual day-to-day differences. These day-to-day variations in gastric emptying must be considered in interpreting individual study results.