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- Persson, Mikael, et al.
(author)
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[Lu-177]pertuzumab : Experimental therapy of HER-2-expressing xenografts
- 2007
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In: Cancer Research. - 0008-5472 .- 1538-7445. ; 67:1, s. 326-331
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Journal article (peer-reviewed)abstract
- Pertuzumab (Omnitarg) is a novel antibody against HER-2, domain II. HER-2 is a tyrosine kinase receptor that is overexpressed in several carcinomas, especially breast cancer. Pertuzumab, labeled with the low-energy beta emitter Lu-177, might be a candidate for targeted radiotherapy of disseminated HER-2-positive micrometastases. The radiolabeled antibody [Lu-177]pertuzumab showed favorable targeting properties in BALB/c (nu/nu) mice with HER-2-overexpressing xenografts. The absorbed dose in tumors was more than five times higher than the absorbed dose in blood and more than seven times the absorbed dose in any other normal organ. Experimental therapy showed that [Lu-177]pertuzumab delayed tumor progression compared with controls (no treatment, P < 0.0001; nonlabeled pertuzumab antibody, P < 0.0001; and Lu-177-labeled irrelevant antibody, P < 0.01). No adverse side effects of the treatment could be detected. Thus, the experimental results support the planning of clinical studies applying [Lu-177]pertuzumab for therapy.
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| 2. |
- Carlsson, Jörgen, et al.
(author)
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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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In: Journal of Neuro-Oncology. - : Springer Science and Business Media LLC. - 0167-594X .- 1573-7373. ; 77:1, s. 33-45
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Journal article (peer-reviewed)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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| 5. |
- Gedda, Hans, et al.
(author)
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Melt-solid interactions in laser cladding and laser casting
- 2005
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In: Metallurgical and materials transactions. B, process metallurgy and materials processing science. - : Springer Science and Business Media LLC. - 1073-5615 .- 1543-1916. ; 36B:5, s. 683-689
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Journal article (peer-reviewed)abstract
- Experimental data in conjunction with mathematical models are used to explain various aspects of laser casting and laser cladding by the preplaced powder method. For increasing speed, the data can be distinguished between substrate melting, dilution-free clad bonding, bond-free casting, and poor contact breaking the melt track into spheres. Results include a thermodynamic explanation of the wide range of process parameters over which dilution-free clad deposits can be produced, as the process switches from heating of the insulating powder to additional cooling when the melt front reaches the substrate. Also, the interaction of the melt pool with the powder bed is analyzed to identify why laser castings have microscopically uneven surfaces and do not bind with the substrate. The advancement of the melt front through the powder layer is governed by heating, melting, and incorporation of each individual grain. Although most powder grains are in the small size range for the case studied, the few particles up to a factor 3 larger delay and therefore govern the front advancement due to much slower melting and surface tension driven incorporation, depending on the particle size in a nonlinear manner.
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| 10. |
- Kullberg, Erika Bohl, et al.
(author)
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An aminoacridine derivative for radionuclide therapy : DNA binding properties studied in a novel cell-free in vitro assay
- 2005
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In: International Journal of Oncology. - 1019-6439 .- 1791-2423. ; 27:5, s. 1355-60
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Journal article (peer-reviewed)abstract
- Radiolabelled DNA-binding compounds can be used to increase the efficiency of radionuclide cancer therapy of disseminated disease. In this work, the aminoacridine compound N-[3-(acridine-9-ylamino)-propyl]-3-iodobenzamide (A3) labelled with the Auger-emitting nuclide 125I using Chloramine-T was studied. Optimal labelling conditions of 125I-A3 were investigated and the interaction with DNA was studied using a novel cell-free in vitro assay with naked human genomic DNA in agarose plugs. This novel assay showed to be simple and reliable. The results verify that 125I-A3 specifically binds DNA with low dissociation and is potent in causing double-strand breaks, yielding 1.0-1.4 breaks per decay. In conclusion, 125I-A3 is a most suitable DNA-binding compound for future therapeutic studies of Auger-electron emitters like 125I.
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