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    • Plusieurs versions

    In vitro evaluation of avidin antibody pretargeting using 211 At‐labeled and biotinylated poly‐L‐lysine as effector molecule

    Frost, Sofia Hl, Jensen, Holger, Lindegren, Sture
    Cancer, 15 February 2010, Vol.116(S4), pp.1101-1110 [Revue évaluée par les pairs]

    • Plusieurs versions

    Binding Affinity, Specificity and Comparative Biodistribution of the Parental Murine Monoclonal Antibody MX35 (Anti-NaPi2b) and Its Humanized Version Rebmab200

    Lindegren, Sture, Andrade, Luciana N S, Bäck, Tom, Machado, Camila Maria L, Horta, Bruno Brasil, Buchpiguel, Carlos, Moro, Ana Maria, Okamoto, Oswaldo Keith, Jacobsson, Lars, Cederkrantz, Elin, Washiyama, Kohshin, Aneheim, Emma, Palm, Stig, Jensen, Holger, Tuma, Maria Carolina B, Chammas, Roger, Hultborn, Ragnar, Albertsson, Per
    PloS one, 2015, Vol.10(5), pp.e0126298 [Revue évaluée par les pairs]

    • Plusieurs versions

    Synthesis and Evaluation of Astatinated N‑[2-(Maleimido)ethyl]-3-(trimethylstannyl)benzamide Immunoconjugates

    Aneheim, Emma, Gustafsson, Anna, Albertsson, Per, Bäck, Tom, Jensen, Holger, Palm, Stig, Svedhem, Sofia, Lindegren, Sture
    Bioconjugate chemistry, 16 March 2016, Vol.27(3), pp.688-697 [Revue évaluée par les pairs]

    • Plusieurs versions

    Comparison of therapeutic efficacy and biodistribution of 213Bi- and 211At-labeled monoclonal antibody MX35 in an ovarian cancer model

    Gustafsson, Anna M.E, Bäck, Tom, Elgqvist, Jörgen, Jacobsson, Lars, Hultborn, Ragnar, Albertsson, Per, Morgenstern, Alfred, Bruchertseifer, Frank, Jensen, Holger, Lindegren, Sture
    Nuclear medicine and biology, 2012, Vol.39(1), pp.15-22 [Revue évaluée par les pairs]

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    Intraperitoneal Alpha-Radioimmunotherapy of Advanced Ovarian Cancer in Nude Mice Using Different High Specific Activities

    Elgqvist, Jorgen, Ahlberg, Daniel, Andersson, Hakan, Jensen, Holger, Johansson, Bengt R, Kahu, Helena, Olsson, Marita, Lindegren, Sture
    World journal of oncology, June 2010, Vol.1(3), pp.101-110 [Revue évaluée par les pairs]

    • Plusieurs versions

    Therapeutic Efficacy of Astatine-211–Labeled Trastuzumab on Radioresistant SKOV-3 Tumors in Nude Mice

    Palm, Stig, Bäck, Tom, Claesson, Ingela, Danielsson, Anna, Elgqvist, Jörgen, Frost, Sofia, Hultborn, Ragnar, Jensen, Holger, Lindegren, Sture, Jacobsson, Lars
    International journal of radiation oncology, biology, physics, 2007, Vol.69(2), pp.572-579 [Revue évaluée par les pairs]

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    Astatine-211-labeled antibodies for treatment of disseminated ovarian cancer: an overview of results in an ovarian tumor model

    Andersson, Håkan, Elgqvist, Jörgen, Horvath, György, Hultborn, Ragnar, Jacobsson, Lars, Jensen, Holger, Karlsson, Börje, Lindegren, Sture, Palm, Stig
    Clinical cancer research : an official journal of the American Association for Cancer Research, 01 September 2003, Vol.9(10 Pt 2), pp.3914S-21S [Revue évaluée par les pairs]
    MEDLINE/PubMed (U.S. National Library of Medicine)
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    Titre: Astatine-211-labeled antibodies for treatment of disseminated ovarian cancer: an overview of results in an ovarian tumor model
    Auteur: Andersson, Håkan; Elgqvist, Jörgen; Horvath, György; Hultborn, Ragnar; Jacobsson, Lars; Jensen, Holger; Karlsson, Börje; Lindegren, Sture; Palm, Stig
    Sujet: Astatine -- Therapeutic Use ; Isotopes -- Therapeutic Use ; Ovarian Neoplasms -- Radiotherapy ; Radioimmunotherapy -- Methods
    Description: The aim of the study was to establish and refine a preclinical model to alpha-immunoradiotherapy of ovarian cancer. At-211 was produced by cyclotron irradiation of a bismuth-209 target and isolated using a novel dry distillation procedure. Monoclonal antibodies were radiohalogenated with the intermediate reagent N-succinimidyl 3-(trimethylstannyl)benzoate and characterized in terms of radiochemical yield and in vitro binding properties. In vitro OVCAR-3 cells were irradiated using an external Cobalt-60 beam, as reference, or At-211-albumin and labeled antibody. Growth assays were used to establish cell survival. A Monte Carlo program was developed to simulate the energy imparted and the track length distribution. Nude mice were used for studies of WBC depression, with various activities of Tc-99m antibodies, as reference, and At-211 antibodies. In efficacy studies, OVCAR-3 cells were inoculated i.p., and animals were treated 2 weeks later. The animals were either dissected 6 weeks later or followed-up for long-term survival. A rapid distillation procedure, as well as a rapid and high-yield, single-pot labeling procedure, was achieved. From growth inhibition data, the relative biological effectiveness of the alpha-emission for OVCAR-3 cells was estimated to be approximately 5, which is in the same range as found in vivo for hematological toxicity. At-211 MOv18 was found to effectively inhibit the development of tumors and ascites, also resulting in long-term survival without significant toxic effect. Use of the short-range, high-linear energy transfer alpha-emitter At-211 conjugated to a surface epitope-recognizing monoclonal antibody appears to be highly efficient without significant toxicity in a mouse peritoneal tumor model, urging a Phase I clinical trial.
    Fait partie de: Clinical cancer research : an official journal of the American Association for Cancer Research, 01 September 2003, Vol.9(10 Pt 2), pp.3914S-21S
    Identifiant: 1078-0432 (ISSN); 14506189 Version (PMID)

    • Plusieurs versions

    Administered activity and metastatic cure probability during radioimmunotherapy of ovarian cancer in nude mice with {sup 211}At-MX35 F(ab'){sub 2}

    Elgqvist, Joergen, Andersson, Hakan, Bernhardt, Peter, Baeck, Tom, Claesson, Ingela, Hultborn, Ragnar, Jensen, Holger, Johansson, Bengt R, Lindegren, Sture, Olsson, Marita, Palm, Stig, Warnhammar, Elisabet, Jacobsson, Lars
    International Journal of Radiation Oncology, Biology and Physics, 15 November 2006, Vol.66(4) [Revue évaluée par les pairs]

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    Direct procedure for the production of 211At-labeled antibodies with an epsilon-lysyl-3-(trimethylstannyl)benzamide immunoconjugate

    Lindegren, Sture, Frost, Sofia, Bäck, Tom, Haglund, Elin, Elgqvist, Jörgen, Jensen, Holger
    Journal of nuclear medicine : official publication, Society of Nuclear Medicine, September 2008, Vol.49(9), pp.1537-45 [Revue évaluée par les pairs]
    MEDLINE/PubMed (U.S. National Library of Medicine)
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    Titre: Direct procedure for the production of 211At-labeled antibodies with an epsilon-lysyl-3-(trimethylstannyl)benzamide immunoconjugate
    Auteur: Lindegren, Sture; Frost, Sofia; Bäck, Tom; Haglund, Elin; Elgqvist, Jörgen; Jensen, Holger
    Sujet: Antibodies, Monoclonal -- Chemistry ; Astatine -- Chemistry ; Benzamides -- Chemistry
    Description: (211)At-labeled tumor-specific antibodies have long been considered for the treatment of disseminated cancer. However, the limited availability of the nuclide and the poor efficacy of labeling procedures at clinical activity levels present major obstacles to their use. This study evaluated a procedure for the direct astatination of antibodies for the production of clinical activity levels. The monoclonal antibody trastuzumab was conjugated with the reagent N-succinimidyl-3-(trimethylstannyl)benzoate, and the immunoconjugate was labeled with astatine. Before astatination of the conjugated antibody, the nuclide was activated with N-iodosuccinimide. The labeling reaction was evaluated in terms of reaction time, volume of reaction solvent, immunoconjugate concentration, and applied activity. The quality of the astatinated antibodies was determined by in vitro analysis and biodistribution studies in nude mice. The reaction proceeded almost instantaneously, and the results indicated a low dependence on immunoconjugate concentration and applied activity. Radiochemical labeling yields were in the range of 68%-81%, and a specific radioactivity of up to 1 GBq/mg could be achieved. Stability and radiochemical purity were equal to or better than those attained with a conventional 2-step procedure. Dissociation constants for directly astatinated, conventionally astatinated, and radioiodinated trastuzumab were 1.0+/-0.06 (mean+/-SD), 0.44+/-0.06, and 0.29+/-0.02 nM, respectively. The tissue distribution in non-tumor-bearing nude mice revealed only minor differences in organ uptake relative to that obtained with the conventional method. The direct astatination procedure enables the high-yield production of astatinated antibodies with radioactivity in the amounts required for clinical applications.
    Fait partie de: Journal of nuclear medicine : official publication, Society of Nuclear Medicine, September 2008, Vol.49(9), pp.1537-45
    Identifiant: 0161-5505 (ISSN); 18703591 Version (PMID); 10.2967/jnumed.107.049833 (DOI)

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    211At radioimmunotherapy of subcutaneous human ovarian cancer xenografts: evaluation of relative biologic effectiveness of an alpha-emitter in vivo

    Bäck, Tom, Andersson, Håkan, Divgi, Chaitanya R, Hultborn, Ragnar, Jensen, Holger, Lindegren, Sture, Palm, Stig, Jacobsson, Lars
    Journal of nuclear medicine : official publication, Society of Nuclear Medicine, December 2005, Vol.46(12), pp.2061-7 [Revue évaluée par les pairs]
    MEDLINE/PubMed (U.S. National Library of Medicine)
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    Titre: 211At radioimmunotherapy of subcutaneous human ovarian cancer xenografts: evaluation of relative biologic effectiveness of an alpha-emitter in vivo
    Auteur: Bäck, Tom; Andersson, Håkan; Divgi, Chaitanya R; Hultborn, Ragnar; Jensen, Holger; Lindegren, Sture; Palm, Stig; Jacobsson, Lars
    Sujet: Astatine -- Therapeutic Use ; Isotopes -- Therapeutic Use ; Ovarian Neoplasms -- Radiotherapy ; Radioimmunotherapy -- Methods ; Radioisotopes -- Pharmacology
    Description: The use of alpha-particle emitters in radioimmunotherapy (RIT) appears to be promising. We previously obtained convincing results in the treatment of microscopic intraperitoneal ovarian cancer in nude mice by using the alpha-emitter 211At. This study was performed to evaluate the relative biological effectiveness (RBE) of 211At compared with that of 60Co gamma-irradiation in an RIT model. Our endpoint was growth inhibition (GI) of subcutaneous xenografts. GI after irradiation was studied with subcutaneous xenografts of the human ovarian cancer cell line NIH:OVCAR-3 implanted in nude mice. The animals received an intravenous injection of 211At-labeled monoclonal antibody MX35 F(ab')2 at different levels of radioactivity (0.33, 0.65, and 0.90 MBq). Control mice received unlabeled MX35 F(ab')2 only. To calculate the mean absorbed dose to tumor, a separate biodistribution study established the uptake of 211At in tumors and organs at different times after injection. External irradiation of the tumors was performed with 60Co. Tumor growth was monitored, and the normalized tumor volume (NTV) was calculated for each tumor. GI was defined by dividing the NTV values by the fitted NTV curve obtained from the corresponding control mice. To compare the biologic effects of the 2 radiation qualities, the mean value for GI (from day 8 to day 23) was plotted for each tumor as a function of its corresponding absorbed dose. From exponential fits of these curves,... The biodistribution study showed the uptake of the immunoconjugate by the tumor (amount of injected radioactivity per gram) to be 14% after 7 h. At 40 h, the ratio of uptake in tumors to uptake in blood reached a maximum value of 6.2. The administered activities of 211At corresponded to doses absorbed by tumors of 1.35, 2.65, and 3.70 Gy. The value (mean+/-SEM) for D37 was 1.59+/-0.08 Gy. Tumor growth after 60Co external irradiation showed a value for D37 of 7.65+/-1.0 Gy. The corresponding RBE of 211At irradiation was 4.8+/-0.7. Using a tumor GI model in nude mice, we were able to derive an RBE of alpha-particle RIT with 211At. The RBE was found to be 4.8+/-0.7.
    Fait partie de: Journal of nuclear medicine : official publication, Society of Nuclear Medicine, December 2005, Vol.46(12), pp.2061-7
    Identifiant: 0161-5505 (ISSN); 16330571 Version (PMID)