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    • Plusieurs versions

    Evaluation of therapeutic efficacy of 211At-labeled farletuzumab in an intraperitoneal mouse model of disseminated ovarian cancer

    Palm, Stig, Bäck, Tom, Aneheim, Emma, Hallqvist, Andreas, Hultborn, Ragnar, Jacobsson, Lars, Jensen, Holger, Lindegren, Sture, Albertsson, Per
    Translational oncology, January 2021, Vol.14(1) [Revue évaluée par les pairs]

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    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]

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    Absorbed Doses and Risk Estimates of 211At-MX35 F(ab')2 in Intraperitoneal Therapy of Ovarian Cancer Patients

    Cederkrantz, Elin, Andersson, Håkan, Bernhardt, Peter, Bäck, Tom, Hultborn, Ragnar, Jacobsson, Lars, Jensen, Holger, Lindegren, Sture, Ljungberg, Michael, Magnander, Tobias, Palm, Stig, Albertsson, Per
    International journal of radiation oncology, biology, physics, 01 November 2015, Vol.93(3), pp.569-576 [Revue évaluée par les pairs]

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    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]

    • 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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    Administered activity and metastatic cure probability during radioimmunotherapy of ovarian cancer in nude mice with 211At-MX35 F(ab′) 2

    Elgqvist, Jörgen, Andersson, Håkan, Bernhardt, Peter, Bäck, 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, physics, 2006, Vol.66(4), pp.1228-1237 [Revue évaluée par les pairs]
    ScienceDirect Journals (Elsevier)
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    Titre: Administered activity and metastatic cure probability during radioimmunotherapy of ovarian cancer in nude mice with 211At-MX35 F(ab′) 2
    Auteur: Elgqvist, Jörgen; Andersson, Håkan; Bernhardt, Peter; Bäck, Tom; Claesson, Ingela; Hultborn, Ragnar; Jensen, Holger; Johansson, Bengt R; Lindegren, Sture; Olsson, Marita; Palm, Stig; Warnhammar, Elisabet; Jacobsson, Lars
    Sujet: Ovarian Cancer ; Radioimmunotherapy ; Dosimetry ; Mx35 ; Astatine ; Ovarian Cancer ; Radioimmunotherapy ; Dosimetry ; Mx35 ; Astatine ; Medicine
    Description: Purpose: To elucidate the therapeutic efficacy of α-radioimmunotherapy of ovarian cancer in mice. This study: (i) estimated the minimum required activity (MRA), giving a reasonable high therapeutic efficacy; and (ii) calculated the specific energy to tumor cell nuclei and the metastatic cure probability (MCP) using various assumptions regarding monoclonal-antibody (mAb) distribution in measured tumors. The study was performed using the α-particle emitter Astatine-211 ( 211At) labeled to the mAb MX35 F(ab′) 2. Methods and Materials: Animals were inoculated intraperitoneally with ∼1 × 10 7 cells of the cell line NIH:OVCAR-3. Four weeks later animals were treated with 25, 50, 100, or 200 kBq 211At-MX35 F(ab′) 2 ( n = 74). Another group of animals was treated with a nonspecific mAb: 100 kBq 211At-Rituximab F(ab′) 2 ( n = 18). Eight weeks after treatment the animals were sacrificed and presence of macro- and microscopic tumors...
    Fait partie de: International journal of radiation oncology, biology, physics, 2006, Vol.66(4), pp.1228-1237
    Identifiant: 0360-3016 (ISSN); 1879-355X (E-ISSN); 10.1016/j.ijrobp.2006.07.003 (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)

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    Myelotoxicity and RBE of 211At-conjugated monoclonal antibodies compared with 99mTc-conjugated monoclonal antibodies and 60Co irradiation in nude mice

    Elgqvist, Jörgen, Bernhardt, Peter, Hultborn, Ragnar, Jensen, Holger, Karlsson, Börje, Lindegren, Sture, Warnhammar, Elisabet, Jacobsson, Lars
    Journal of nuclear medicine : official publication, Society of Nuclear Medicine, March 2005, Vol.46(3), pp.464-71 [Revue évaluée par les pairs]
    MEDLINE/PubMed (U.S. National Library of Medicine)
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    Titre: Myelotoxicity and RBE of 211At-conjugated monoclonal antibodies compared with 99mTc-conjugated monoclonal antibodies and 60Co irradiation in nude mice
    Auteur: Elgqvist, Jörgen; Bernhardt, Peter; Hultborn, Ragnar; Jensen, Holger; Karlsson, Börje; Lindegren, Sture; Warnhammar, Elisabet; Jacobsson, Lars
    Sujet: Relative Biological Effectiveness ; Astatine -- Adverse Effects ; Bone Marrow -- Radiation Effects ; Radiometry -- Methods ; Technetium -- Adverse Effects
    Description: The rationale of this study was to determine the myelotoxicity in nude mice of the alpha-emitter 211At conjugated to monoclonal antibodies (mAbs) and to compare the effect with an electron emitter, (99m)Tc, and external irradiation from a 60Co source, for estimation of the relative biological effectiveness (RBE). 211At and (99m)Tc were conjugated to the IgG1 mAbs MX35 and 88BV59. Nude female BALB/c mice, 8- to 12-wk old, were injected intraperitoneally or intravenously. The biodistribution was determined 3, 6, and 18 h after injection. The bone-to-blood and bone marrow-to-blood activity concentration ratios (BBLR and BMBLR, respectively) were determined for simultaneously injected 211At- and (99m)Tc-mAbs. Bone marrow samples were taken from the femur. For each mouse, the whole-body retention was measured as well as the blood activity by repeated blood samples from the tail vein (0), 1, 3, 6, 12, and 18 h after injection. External-beam irradiation from a 60Co source was also performed at 3 different dose levels. White blood cell (WBC) counts, red blood cell counts, platelet counts, and hemoglobin were determined for each mouse initially and on days 1, 4, 5, 7, 15, 22, and 27 after injection. The calculations of the absorbed dose to the bone marrow were based on the BBLR, BMBLR, the cumulated activities,... The BMBLR was 0.58 +/- 0.06 and 0.56 +/- 0.06 for the 211At- and (99m)Tc-mAbs, respectively. No significant variation in BMBLR with time was found. The absorbed fractions for alpha-particles and electrons in the bone marrow were 0.88 and 0.75, respectively. The mean absorbed fractions of the photons from (99m)Tc were 0.033 and 0.52 for 140 and 18.3 keV, respectively. When different amounts of 211At- and (99m)Tc-mAbs (0.09-1.3 and 250-1,300 MBq, respectively) were administered intraperitoneally or intravenously, corresponding to absorbed doses to the bone marrow of 0.01-0.60 and 0.39-1.92 Gy, respectively, the WBC counts was suppressed by 1%-90% and 23%-89%, respectively. When external-beam irradiation with a 60Co source was performed to absorbed doses of 1.4, 1.9, and 2.4 Gy, the WBC counts was suppressed by 47%-90%. These results indicate a myelotoxic in vivo RBE of 3.4 +/- 0.6 for alpha-particles compared with (99m)Tc and 5.0 +/- 0.9 compared with 60Co irradiation. The effect on the WBC counts from bone marrow irradiation with 211At-mAbs indicates an in vivo RBE of 3.4 +/- 0.6 in comparison with (99m)Tc-mAbs. The RBE value compared with external irradiation is 5.0 +/- 0.9.
    Fait partie de: Journal of nuclear medicine : official publication, Society of Nuclear Medicine, March 2005, Vol.46(3), pp.464-71
    Identifiant: 0161-5505 (ISSN); 15750160 Version (PMID)