| 1. |
- Carlsson, Jörgen, et al.
(författare)
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Conjugate chemistry and cellular processing of EGF-dextran
- 1999
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Ingår i: Acta Oncologica. - 0284-186X .- 1651-226X. ; 38:3, s. 313-321
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Tidskriftsartikel (refereegranskat)abstract
- 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.
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| 2. |
- Carlsson, Jörgen, et al.
(författare)
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Planning for intracavitary anti-EGFR radionuclide therapy of gliomas : Literature review and data on EGFR expression
- 2006
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Ingår i: Journal of Neuro-Oncology. - : Springer Science and Business Media LLC. - 0167-594X .- 1573-7373. ; 77:1, s. 33-45
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Tidskriftsartikel (refereegranskat)abstract
- Targeting with radionuclide labelled substances that bind specifically to the epidermal growth factor receptor, EGFR, is considered for intracavitary therapy of EGFR-positive glioblastoma multiforme, GBM. Relevant literature is reviewed and examples of EGFR expression in GBM are given. The therapeutical efforts made so far using intracavitary anti-tenascin radionuclide therapy of GBM have given limited effects, probably due to low radiation doses to the migrating glioma cells in the brain. Low radiation doses might be due to limited penetration of the targeting agents or heterogeneity in the expression of the target structure. In this article we focus on the possibilities to target EGFR on the tumour cells instead of an extracellular matrix component. There seems to be a lack of knowledge on the degree of intratumoral variation of EGFR expression in GBM, although the expression seemed rather homogeneous over large areas in most of the examples (n=16) presented from our laboratory. The observed homogeneity was surprising considering the genomic instability and heterogeneity that generally characterises highly malignant tumours. However, overexpression of EGFR is, at least in primary GBMs, one of the steps in the development of malignancy, and tumour cells that lose or downregulate EGFR will probably be outgrown in an expanding tumour cell population. Thus, loss of EGFR expression might not be the critical factor for successful intracavitary radionuclide therapy. Instead, it is likely that the penetration properties of the targeting agents are critical, and detailed studies on this are urgent.
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| 3. |
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| 4. |
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| 5. |
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| 6. |
- Stenerlöw, Bo, et al.
(författare)
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Basic radiotherapy research
- 1996
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Ingår i: TSL Progress Report. ; 94-95
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Annan publikation (övrigt vetenskapligt/konstnärligt)
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| 7. |
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| 8. |
- Stenerlöw, Bo, et al.
(författare)
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Biomedical Radiation Research
- 1998
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Ingår i: TSL Progress Report. ; 96-97
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Annan publikation (övrigt vetenskapligt/konstnärligt)
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| 9. |
- Stenerlöw, Bo, et al.
(författare)
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DNA fragmentation
- 2000
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Ingår i: TSL Progress Report. ; 98-99
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Annan publikation (övrigt vetenskapligt/konstnärligt)
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| 10. |
- Sundberg, Åsa Liljegren, et al.
(författare)
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[111In]Bz-DTPA-hEGF : Preparation and in vitro characterization of a potential anti-glioblastoma targeting agent
- 2003
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Ingår i: Cancer Biotherapy and Radiopharmaceuticals. - : Mary Ann Liebert Inc. - 1084-9785 .- 1557-8852. ; 18:4, s. 643-54
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Tidskriftsartikel (refereegranskat)abstract
- The overexpression of epidermal growth factor receptors, EGFR, in glioblastomas is well documented. Hence, the EGFR can be used as target structure for a specific targeting of glioblastomas. Both radiolabeled anti-EGFR antibodies and the natural ligand EGF are candidate agents for targeting. However, EGF, which has a rather low molecular weight (6 kDa), might have better tissue penetration properties through both normal tissue and tumors in comparison with anti-EGF antibodies and their fragments. The aim of this study was to prepare and evaluate in vitro an EGF-based antiglioma conjugate with residualizing label. Human recombinant EGF (hEGF) was coupled to isothiocyanate-benzyl-DTPA. The conjugate was purified from unreacted chelator using solid-phase extraction and labeled with (111)In. The labeling yield was 87% +/- 7%. The label was reasonably stable; the transchelation of (111)In to serum proteins was about 5% after incubation at 37 degrees C during 24 hours. The obtained [(111)In]benzyl-DTPA-hEGF conjugate was characterized in vitro using the EGFR expressing glioma cell line U343MGaCl2:6. The binding affinity, internalization, and retention of the conjugate were studied. The conjugate had receptor specific binding and the radioactivity was quickly internalized. The intracellular retention of radioactivity after interrupted incubation with conjugate was 71% +/- 1% and 59% +/- 1.5% at 24 and 45 hours, respectively. The dissociation constant was estimated to 2.0 nM. The results indicate that [(111)In]benzyl-DTPA-hEGF is a potential candidate for targeting glioblastoma cells, possibly using locoregional injection.
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