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    • Plusieurs versions

    N-[2-(maleimido)ethyl]-3-(trimethylstannyl)benzamide, a molecule for radiohalogenation of proteins and peptides

    Aneheim, Emma, Foreman, Mark R. Stj, Jensen, Holger, Lindegren, Sture
    Applied radiation and isotopes, February 2015, Vol.96, pp.1-5 [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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    Automated astatination of biomolecules - a stepping stone towards multicenter clinical trials

    Aneheim, Emma, Albertsson, Per, Bäck, Tom, Jensen, Holger, Palm, Stig, Lindegren, Sture
    Scientific Reports (Nature Publisher Group), Jul 2015, Vol.5, p.12025 [Revue évaluée par les pairs]

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    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)

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    Multifunctional Clickable Reagents for Rapid Bioorthogonal Astatination and Radio‐Crosslinking

    Denk, Christoph, Wilkovitsch, Martin, Aneheim, Emma, Herth, Matthias M., Jensen, Holger, Lindegren, Sture, Mikula, Hannes
    ChemPlusChem, July 2019, Vol.84(7), pp.774-774 [Revue évaluée par les pairs]

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    Multifunctional Clickable Reagents for Rapid Bioorthogonal Astatination and Radio‐Crosslinking

    Denk, Christoph, Wilkovitsch, Martin, Aneheim, Emma, Herth, Matthias M., Jensen, Holger, Lindegren, Sture, Mikula, Hannes
    ChemPlusChem, July 2019, Vol.84(7), pp.775-778 [Revue évaluée par les pairs]

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    Combined effect of gefitinib ('Iressa', ZD1839) and targeted radiotherapy with 211 At-EGF

    Sundberg, Åsa, Almqvist, Ylva, Orlova, Anna, Blomquist, Erik, Jensen, Holger, Gedda, Lars, Tolmachev, Vladimir, Carlsson, Jörgen
    European Journal of Nuclear Medicine and Molecular Imaging, 2003, Vol.30(10), pp.1348-1356 [Revue évaluée par les pairs]

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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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    Intraperitoneal alpha-particle radioimmunotherapy of ovarian cancer patients: pharmacokinetics and dosimetry of (211)At-MX35 F(ab')2--a phase I study

    Andersson, Håkan, Cederkrantz, Elin, Bäck, Tom, Divgi, Chaitanya, Elgqvist, Jörgen, Himmelman, Jakob, Horvath, György, Jacobsson, Lars, Jensen, Holger, Lindegren, Sture, Palm, Stig, Hultborn, Ragnar
    Journal of nuclear medicine : official publication, Society of Nuclear Medicine, July 2009, Vol.50(7), pp.1153-60 [Revue évaluée par les pairs]
    MEDLINE/PubMed (U.S. National Library of Medicine)
    Disponible
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    Titre: Intraperitoneal alpha-particle radioimmunotherapy of ovarian cancer patients: pharmacokinetics and dosimetry of (211)At-MX35 F(ab')2--a phase I study
    Auteur: Andersson, Håkan; Cederkrantz, Elin; Bäck, Tom; Divgi, Chaitanya; Elgqvist, Jörgen; Himmelman, Jakob; Horvath, György; Jacobsson, Lars; Jensen, Holger; Lindegren, Sture; Palm, Stig; Hultborn, Ragnar
    Sujet: Body Burden ; Radiometry ; Radiotherapy Dosage ; Antibodies, Monoclonal -- Therapeutic Use ; Astatine -- Therapeutic Use ; Ovarian Neoplasms -- Metabolism
    Description: The alpha-emitter (211)At labeled to a monoclonal antibody has proven safe and effective in treating microscopic ovarian cancer in the abdominal cavity of mice. Women in complete clinical remission after second-line chemotherapy for recurrent ovarian carcinoma were enrolled in a phase I study. The aim was to determine the pharmacokinetics for assessing absorbed dose to normal tissues and investigating toxicity. Nine patients underwent laparoscopy 2-5 d before the therapy; a peritoneal catheter was inserted, and the abdominal cavity was inspected to exclude the presence of macroscopic tumor growth or major adhesions. (211)At was labeled to MX35 F(ab')(2) using the reagent N-succinimidyl-3-(trimethylstannyl)-benzoate. Patients were infused with (211)At-MX35 F(ab')(2) (22.4-101 MBq/L) in dialysis solution via the peritoneal catheter. gamma-Camera scans were acquired on 3-5 occasions after infusion, and a SPECT scan was acquired at 6 h. Samples of blood, urine, and peritoneal fluid were collected at 1-48 h. Hematology and renal and thyroid function were followed for a median of 23 mo. Pharmacokinetics and dosimetric results were related to the initial activity concentration (IC) of the infused solution. The decay-corrected activity concentration decreased with time in the peritoneal fluid to 50% IC at 24 h, increased in serum to 6% IC at 45 h, and increased in the thyroid to 127% +/- 63% IC at 20 h without blocking and less than 20% IC with blocking. No other organ uptakes could be detected. The cumulative urinary excretion was 40 kBq/(MBq/L) at 24 h. The estimated absorbed dose to the peritoneum was 15.6 +/- 1.0 mGy/(MBq/L), to red bone marrow it was 0.14 +/- 0.04 mGy/(MBq/L), to the urinary bladder wall it was 0.77 +/- 0.19 mGy/(MBq/L), to the unblocked thyroid it was 24.7 +/- 11.1 mGy/(MBq/L), and to the blocked thyroid it was 1.4 +/- 1.6 mGy/(MBq/L) (mean +/- SD). No adverse effects were observed either subjectively or in laboratory parameters. This study indicates that by intraperitoneal administration of (211)At-MX35 F(ab')(2) it is possible to achieve therapeutic absorbed doses in microscopic tumor clusters without significant toxicity.
    Fait partie de: Journal of nuclear medicine : official publication, Society of Nuclear Medicine, July 2009, Vol.50(7), pp.1153-60
    Identifiant: 0161-5505 (ISSN); 19525452 Version (PMID); 10.2967/jnumed.109.062604 (DOI)