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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]

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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]

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    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]
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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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    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]
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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)

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    Alpha-radioimmunotherapy of intraperitoneally growing OVCAR-3 tumors of variable dimensions: Outcome related to measured tumor size and mean absorbed dose

    Elgqvist, Jörgen, Andersson, Håkan, Bäck, Tom, Claesson, Ingela, Hultborn, Ragnar, Jensen, Holger, Johansson, Bengt R, Lindegren, Sture, Olsson, Marita, Palm, Stig, Warnhammar, Elisabet, Jacobsson, Lars
    Journal of nuclear medicine : official publication, Society of Nuclear Medicine, August 2006, Vol.47(8), pp.1342-50 [Revue évaluée par les pairs]
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    Titre: Alpha-radioimmunotherapy of intraperitoneally growing OVCAR-3 tumors of variable dimensions: Outcome related to measured tumor size and mean absorbed dose
    Auteur: Elgqvist, Jörgen; Andersson, Håkan; Bäck, Tom; Claesson, Ingela; Hultborn, Ragnar; Jensen, Holger; Johansson, Bengt R; Lindegren, Sture; Olsson, Marita; Palm, Stig; Warnhammar, Elisabet; Jacobsson, Lars
    Sujet: Ovarian Neoplasms -- Diagnostic Imaging ; Radioimmunotherapy -- Methods
    Description: The purpose of this work was to (a) investigate the efficacy of radioimmunotherapy using 211At-MX35 F(ab')2 or 211At-Rituximab F(ab')2 (nonspecific antibody) against differently advanced ovarian cancer in mice; (b) image the tumor growth on the peritoneum; and (c) calculate the specific energy and mean absorbed dose to tumors and critical organs. Two experiments with 5-wk-old nude mice (n = 100 + 93), intraperitoneally inoculated with approximately 1 x 10(7) NIH:OVCAR-3 cells, were done. At either 1, 3, 4, 5, or 7 wk after inoculation animals were intraperitoneally treated with approximately 400 kBq 211At-MX35 F(ab')2 (n = 50 + 45), approximately 400 kBq 211At-Rituximab F(ab')2 (n = 25 + 24), or unlabeled Rituximab F(ab')2 (n = 25 + 24). At the time of treatment 29 animals were sacrificed and biopsies were taken for determination of tumor sizes using scanning electron microscopy (SEM). Eight weeks after each treatment the animals were sacrificed and the presence of macro- and microscopic tumors and ascites was determined. The specific energy and mean absorbed dose to tumors were calculated. The activity concentration was measured in critical organs and abdominal fluid. When given treatment 1, 3, 4, 5, or 7 wk after cell inoculation the tumor-free fraction (TFF) was 95%, 68%, 58%, 47%, 26%, and 100%, 80%, 20%, 20%, and 0% when treated with 211At-MX35 F(ab')2 or 211At-Rituximab F(ab')2, respectively. The SEM images revealed maximum tumor radius of approximately 30 mum 1 wk after cell inoculation, increasing to approximately 340 mum at 7 wk. Specific energy to cell nuclei varied between 0 and approximately 540 Gy, depending on assumptions regarding activity distribution and tumor size. The mean absorbed dose to thyroid, kidneys, and bone marrow was approximately 35, approximately 4, and approximately 0.3 Gy, respectively. Treatment with 211At-MX35 F(ab')2 or 211At-Rituximab F(ab')2 resulted in a TFF of 95%-100% when the tumor radius was 22 Gy) from the activity bound to the tumor surface and probably some contribution from penetrating activity.
    Fait partie de: Journal of nuclear medicine : official publication, Society of Nuclear Medicine, August 2006, Vol.47(8), pp.1342-50
    Identifiant: 0161-5505 (ISSN); 16883015 Version (PMID)

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    Fractionated radioimmunotherapy of intraperitoneally growing ovarian cancer in nude mice with 211At-MX35 F(ab′) 2: therapeutic efficacy and myelotoxicity

    Elgqvist, Jörgen, Andersson, Håkan, Bäck, Tom, Claesson, Ingela, Hultborn, Ragnar, Jensen, Holger, Lindegren, Sture, Olsson, Marita, Palm, Stig, Warnhammar, Elisabet, Jacobsson, Lars
    Nuclear medicine and biology, 2006, Vol.33(8), pp.1065-1072 [Revue évaluée par les pairs]

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    Intraperitoneal α-Emitting Radioimmunotherapy with At in Relapsed Ovarian Cancer: Long-Term Follow-up with Individual Absorbed Dose Estimations

    Hallqvist, Andreas, Bergmark, Karin, Bäck, Tom, Andersson, Håkan, Dahm-Kähler, Pernilla, Johansson, Mia, Lindegren, Sture, Jensen, Holger, Jacobsson, Lars, Hultborn, Ragnar, Palm, Stig, Albertsson, Per
    Journal of nuclear medicine : official publication, Society of Nuclear Medicine, August 2019, Vol.60(8), pp.1073-1079 [Revue évaluée par les pairs]
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    Titre: Intraperitoneal α-Emitting Radioimmunotherapy with At in Relapsed Ovarian Cancer: Long-Term Follow-up with Individual Absorbed Dose Estimations
    Auteur: Hallqvist, Andreas; Bergmark, Karin; Bäck, Tom; Andersson, Håkan; Dahm-Kähler, Pernilla; Johansson, Mia; Lindegren, Sture; Jensen, Holger; Jacobsson, Lars; Hultborn, Ragnar; Palm, Stig; Albertsson, Per
    Sujet: Alpha Particle ; Astatine ; Intraperitoneal ; Ovarian Cancer ; Phase I
    Description: Eliminating microscopic residual disease with α-particle radiation is theoretically appealing. After extensive preclinical work with α-particle-emitting At, we performed a phase I trial with intraperitoneal α-particle therapy in epithelial ovarian cancer using At conjugated to MX35, the antigen-binding fragments-F(ab')-of a mouse monoclonal antibody. We now present clinical outcome data and toxicity in a long-term follow-up with individual absorbed dose estimations. Twelve patients with relapsed epithelial ovarian cancer, achieving a second complete or nearly complete response with chemotherapy, received intraperitoneal treatment with escalating (20-215 MBq/L) activity concentrations of At-MX35 F(ab') The activity concentration was escalated to 215 MBq/L without any dose-limiting toxicities. Most toxicities were low-grade and likely related to the treatment procedure, not clearly linked to the α-particle irradiation, with no observed hematologic toxicity. One grade 3 fatigue and 1 grade...
    Fait partie de: Journal of nuclear medicine : official publication, Society of Nuclear Medicine, August 2019, Vol.60(8), pp.1073-1079
    Identifiant: 1535-5667 (E-ISSN); 30683761 Version (PMID); 10.2967/jnumed.118.220384 (DOI)