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BETA
Sjöström, Anna
Alternative names
Publications (9 of 9) Show all publications
Almqvist, Y., Orlova, A., Sjöström, A., Jensen, H. J., Lundqvist, H., Sundin, A. & Tolmachev, V. (2005). In vitro characterization of 211 At-labeled antibody A33: a potential therapeutic agent against metastatic colorectal carcinoma. Cancer Biotherapy and Radiopharmaceuticals, 20(5), 514-523
Open this publication in new window or tab >>In vitro characterization of 211 At-labeled antibody A33: a potential therapeutic agent against metastatic colorectal carcinoma
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2005 (English)In: Cancer Biotherapy and Radiopharmaceuticals, ISSN 1084-9785, E-ISSN 1557-8852, Vol. 20, no 5, p. 514-523Article in journal (Refereed) Published
Abstract [en]

The humanized antibody A33 binds to the A33 antigen, expressed in 95% of primary and metastatic colorectal carcinomas. The restricted pattern of expression in normal tissue makes this antigen a possible target for radioimmunotherapy of colorectal micrometastases. In this study, the A33 antibody was labeled with the therapeutic nuclide 211At using N-succinimidyl para-(tri-methylstannyl)benzoate (SPMB). The in vitro characteristics of the 211At-benzoate-A33 conjugate (211At-A33) were investigated and found to be similar to those of 125I-benzoate-A33 (125I-A33) in different assays. Both conjugates bound with high affinity to SW1222 cells (Kd = 1.7 ± 0.2 nM, and 1.8 ± 0.1 nM for 211At-A33 and 125I-A33, respectively), and both showed good intracellular retention (70% of the radioactivity was still cell associated after 20 hours). The cytotoxic effect of 211At-A33 was also confirmed. After incubation with 211At-A33, SW1222 cells had a survival of approximately 0.3% when exposed to some 150 decays per cell (DPC). The cytotoxic effect was found to be dose-dependent, as cells exposed to only 56 DPC had a survival of approximately 5%. The 211At-A33 conjugate shows promise as a potential radioimmunotherapy agent for treatment of micrometastases originating from colorectal carcinoma.

National Category
Radiology, Nuclear Medicine and Medical Imaging
Identifiers
urn:nbn:se:uu:diva-104544 (URN)10.1089/cbr.2005.20.514 (DOI)16248767 (PubMedID)
Available from: 2009-05-28 Created: 2009-05-28 Last updated: 2017-12-13Bibliographically approved
Orlova, A., Sjöström, A., Lebeda, O., Lundqvist, H., Carlsson, J. & Tolmachev, V. (2004). Targeting against epidermal growth factor receptors: Cellular processing of astatinated EGF after binding to cultured carcinoma cells. Anticancer Research, 24(6), 4035-4042
Open this publication in new window or tab >>Targeting against epidermal growth factor receptors: Cellular processing of astatinated EGF after binding to cultured carcinoma cells
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2004 (English)In: Anticancer Research, ISSN 0250-7005, E-ISSN 1791-7530, Vol. 24, no 6, p. 4035-4042Article in journal (Refereed) Published
Abstract [en]

BACKGROUND:

The alpha-emitting nuclide 211At is of great interest for radionuclide therapy when coupled to a tumor-targeting biomolecule, e.g. epidermal growth factor (EGF) the receptors of which are overexpressed in many malignancies. However, almost no information concerning the cellular processing of astatinated targeting agents is available.

MATERIALS AND METHODS:

We indirectly astatinated EGF ([211At]-benzoate-EGF) and studied its cellular processing in A-431 carcinoma cells in comparison with data concerning [125I]-benzoate-EGF.

RESULTS:

The biological half-life of astatine (3.5 h) was longer than the half-life of the iodine label (1.5 h). The increase of the half-life was due to longer retention of the internalised astatine radioactivity. The maximum accumulation for the astatine label occurred later (4-6h) than that for the iodine label (2-4h), indicating a slower excretion of astatine that was confirmed in experiment with 211At/1251-benzoate-EGF.

CONCLUSION:

The long retention of astatine might be advantageous for radionuclide therapy.

Keywords
Astatine/chemistry/metabolism/*pharmacokinetics, Carcinoma/*metabolism/radiotherapy, Cell Line; Tumor, Cell Membrane/metabolism, Epidermal Growth Factor/metabolism/*pharmacokinetics, Epithelioid Cells/metabolism/pathology, Half-Life, Humans, Iodobenzoates/metabolism/pharmacokinetics, Radiopharmaceuticals/metabolism/*pharmacokinetics, Receptor; Epidermal Growth Factor/*metabolism
National Category
Radiology, Nuclear Medicine and Medical Imaging
Identifiers
urn:nbn:se:uu:diva-72882 (URN)15736449 (PubMedID)
Available from: 2007-03-09 Created: 2007-03-09 Last updated: 2017-12-14Bibliographically approved
Wester, K., Sjöström, A., de la Torre, M., Carlsson, J. & Malmström, P.-U. (2002). HER-2: A possible target for therapy of metastatic urinary bladder carcinoma. Acta Oncologica, 41(3), 282-288
Open this publication in new window or tab >>HER-2: A possible target for therapy of metastatic urinary bladder carcinoma
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2002 (English)In: Acta Oncologica, ISSN 0284-186X, E-ISSN 1651-226X, Vol. 41, no 3, p. 282-288Article in journal (Refereed) Published
Abstract [en]

Human epidermal growth factor receptor 2, HER-2, is overexpressed in various tumours, e.g. breast- and bladder tumours. The aim of this study was to predict the potential use of HER-2 receptors as targets in systemic treatment of disseminated bladder tumours. HER-2 expression was assessed in bladder carcinoma metastases and the corresponding primary tumours, and subsequently compared with the EGFR expression. HER-2 and EGFR expression was analysed by immunohistochemistry in formalin-fixed, paraffin-embedded tissues from 21 patients with metastatic bladder carcinoma. HER-2 was overexpressed in 81% of the primary tumours and in 67% of the metastases. All HER-2-positive metastases were from HER-2-positive primary tumours. The results for EG FR were 71% of both primary and metastases-positive tumours. In 90% of the primary tumours and 86% of the metastases, at least one of the receptors was overexpressed. These results suggest that HER-2 targeted therapy can be considered as an alternative or a complement to other modalities in the treatment of metastatic urinary bladder carcinoma.

National Category
Radiology, Nuclear Medicine and Medical Imaging Urology and Nephrology
Identifiers
urn:nbn:se:uu:diva-64303 (URN)10.1080/02841860260088836 (DOI)12195748 (PubMedID)
Available from: 2008-06-15 Created: 2008-06-15 Last updated: 2017-11-30Bibliographically approved
Orlova, A., Sjöström, A., Ericson, A., Lebeda, O., Lundqvist, H., Carlsson, J. & Tolmachev, V. (2001). Cellular processing of indirectly astatinated and iodinated mAb A33 in SW1222 cultured cells [Review]. Journal of labelled compounds & radiopharmaceuticals, 44(suppl 1), S715-S717
Open this publication in new window or tab >>Cellular processing of indirectly astatinated and iodinated mAb A33 in SW1222 cultured cells
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2001 (English)In: Journal of labelled compounds & radiopharmaceuticals, ISSN 0362-4803, E-ISSN 1099-1344, Vol. 44, no suppl 1, p. S715-S717Article, book review (Other academic) Published
Abstract [en]

In principle, alpha-emitting radionuclides, such as 211At, are more efficient than beta-emitters to inactive single disseminated cancer cells. However, cellular processing of astatinated proteins has not yet been studied in detail. In this study an anti-colorectal cancer monoclonal antibody (mAb) A33 was indirectly labeled with 211At and for comparison with 125I. Binding and retention of radioactivity was studied in the colorectal cancer cell-line SW1222. A similar pattern of binding and retention of the two radiohalogens was seen. The main difference found, that the retention time of astatinated mAb in SW1222 was almost two times longer, might be of advantage in radionuclide therapy.

National Category
Radiology, Nuclear Medicine and Medical Imaging
Identifiers
urn:nbn:se:uu:diva-62607 (URN)10.1002/jlcr.25804401252 (DOI)
Available from: 2008-10-17 Created: 2008-10-17 Last updated: 2017-11-30Bibliographically approved
Orlova, A., Bruskin, A., Sjöström, A., Lundqvist, H., Gedda, L. & Tolmavhev, V. (2000). Cellular processing of 125I- and 111in-labeled epidermal growth factor (EGF) bound to cultured A431 tumor cells [Review]. Nuclear Medicine and Biology, 27(8), 827-835
Open this publication in new window or tab >>Cellular processing of 125I- and 111in-labeled epidermal growth factor (EGF) bound to cultured A431 tumor cells
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2000 (English)In: Nuclear Medicine and Biology, ISSN 0969-8051, E-ISSN 1872-9614, Vol. 27, no 8, p. 827-835Article, book review (Other academic) Published
Abstract [en]

Low molecular weight of epidermal growth factor (EGF) enables better intratumoral penetration in comparison with larger targeting proteins, but the cellular retention of EGF-associated radioactivity is poor for directly iodinated EGF. An attempt was made to improve intracellular retention by the use of metal-diethylenetriaminepentaacetic acid or nonphenolic linker (N-succinimidyl-para-iodobenzoate) as labeling agents. The use of nonphenolic linker did not improve retention of the radioactivity in A431 carcinoma cell line. The use of the radiometal label provided an appreciable prolongation of radioactivity residence inside the cell.

National Category
Radiology, Nuclear Medicine and Medical Imaging
Identifiers
urn:nbn:se:uu:diva-61313 (URN)10.1016/S0969-8051(00)00148-7 (DOI)11150717 (PubMedID)
Available from: 2008-10-17 Created: 2008-10-17 Last updated: 2018-12-04
Orlova, A., Bruskin, A., Sjöström, A., Lundqvist, H., Gedda, L. & Tolmachev, V. (2000). Cellular processing of (125)I- and (111)in-labeled epidermal growth factor(EGF) bound to cultured A431 tumor cells. Nuclear Medicine and Biology, 27(8), 827-35
Open this publication in new window or tab >>Cellular processing of (125)I- and (111)in-labeled epidermal growth factor(EGF) bound to cultured A431 tumor cells
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2000 (English)In: Nuclear Medicine and Biology, ISSN 0969-8051, E-ISSN 1872-9614, Vol. 27, no 8, p. 827-35Article in journal (Refereed) Published
Abstract [en]

Low molecular weight of epidermal growth factor (EGF) enables better intratumoral penetration in comparison with larger targeting proteins, but the cellular retention of EGF-associated radioactivity is poor for directly iodinated EGF. An attempt was made to improve intracellular retention by the use of metal-diethylenetriaminepentaacetic acid or nonphenolic linker (N-succinimidyl-para-iodobenzoate) as labeling agents. The use of nonphenolic linker did not improve retention of the radioactivity in A431 carcinoma cell line. The use of the radiometal label provided an appreciable prolongation of radioactivity residence inside the cell.

Keywords
125I-para-iodo-benzoate, 111In-DTPA, EGF, A431 cells, Intracellular retention
National Category
Medical and Health Sciences
Identifiers
urn:nbn:se:uu:diva-63148 (URN)10.1016/S0969-8051(00)00148-7 (DOI)11150717 (PubMedID)
Available from: 2008-10-17 Created: 2008-10-17 Last updated: 2018-12-04
Carlsson, J., Blomquist, E., Gedda, L., Liljegren, Å., Malmström, P.-U., Sjöström, A., . . . Lundqvist, H. (1999). Conjugate chemistry and cellular processing of EGF-dextran. Acta Oncologica, 38(3), 313-321
Open this publication in new window or tab >>Conjugate chemistry and cellular processing of EGF-dextran
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1999 (English)In: Acta Oncologica, ISSN 0284-186X, E-ISSN 1651-226X, Vol. 38, no 3, p. 313-321Article in journal (Refereed) Published
Abstract [en]

Conjugates with specific binding to the epidermal growth factor receptor, EGFR, of interest for radionuclide based imaging and therapy were prepared using mouse epidermal growth factor, mEGF, and dextran. In one type of conjugate, mEGF was coupled to dextran by reductive amination in which the free amino group on the mEGF N-terminal reacted with the aldehyde group on the reductive end of dextran. The end-end coupled conjugate could be further activated by the cyanopyridinium agent CDAP, thereby introducing tyrosines to the dextran part. In the other type of conjugate, the cyanylating procedure using CDAP was applied, first to activate dextran and then allowing for the amino terminus of mEGF to randomly attach to the dextran. In the latter case, radionuclide-labelled tyrosines or glycines could be added in the same conjugation step. All types of mEGF-dextran conjugates had EGFR-specific binding since the binding could be displaced by an excess of non-radioactive mEGF. The conjugates were to a large extent internalized in the test cells and the associated radioactivity was retained intracellularly for different times depending on both the type of cells and conjugate applied. Different intracellular 'traffic routes' for the radionuclides are discussed as well as applications for both imaging and therapy.

National Category
Radiology, Nuclear Medicine and Medical Imaging
Identifiers
urn:nbn:se:uu:diva-57136 (URN)10380822 (PubMedID)
Available from: 2008-10-17 Created: 2008-10-17 Last updated: 2018-12-04
Sjöström, A., Bue, P., Nilsson, P., Carlsson, J. & Malmstrom, P.-U. (1998). Binding of EGF-dextran conjugates to bladder cancer spheroids [Review]. Eur Urol, 34, 245
Open this publication in new window or tab >>Binding of EGF-dextran conjugates to bladder cancer spheroids
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1998 (English)In: Eur Urol, Vol. 34, p. 245-Article, book review (Other academic) Published
National Category
Medical and Health Sciences
Identifiers
urn:nbn:se:uu:diva-60655 (URN)
Available from: 2008-10-17 Created: 2008-10-17 Last updated: 2014-07-01
Nilsson, P., Gedda, L., Sjöstrom, A., Zhao, Q. & Carlsson, J. (1997). Penetration and Binding of EGF-Dextran Conjugates in Cultured-Cell Spheroids [Review]. European Journal of Cell Biology, 74(suppl. 47), 118-118
Open this publication in new window or tab >>Penetration and Binding of EGF-Dextran Conjugates in Cultured-Cell Spheroids
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1997 (English)In: European Journal of Cell Biology, ISSN 0171-9335, E-ISSN 1618-1298, Vol. 74, no suppl. 47, p. 118-118Article, book review (Other academic) Published
National Category
Radiology, Nuclear Medicine and Medical Imaging
Identifiers
urn:nbn:se:uu:diva-60662 (URN)
Available from: 2008-10-17 Created: 2008-10-17 Last updated: 2018-12-04
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