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Rajecki M Sarparanta M Hakkarainen T Tenhunen M Diaconu I Kuhmonen V Kairemo K Kanerva A Airaksinen AJ Hemminki A 《PloS one》2012,7(3):e32871
Oncolytic adenoviruses can be engineered for better tumor selectivity, gene delivery and be armed for imaging and concentrating radionuclides into tumors for synergistic oncolysis. We constructed Ad5/3-hTERT-hNIS where replication is controlled by hTERT-promoter. Ad5/3-hTERT-hNIS expresses hNIS for imaging of transgene expression and for treatment of infected tumors by radioiodine. Ad5/3-hTERT-hNIS efficiently killed prostate cancer cells and induced iodine uptake in vitro and in vivo after intratumoral virus administration. Survival of mice treated with intravenous Ad5/3-hTERT-hNIS significantly prolonged survival over mock or radioiodine only but the combination of virus with radioiodine was not more effective than virus alone. Temporal and spatial changes in hNIS-expression during therapy were detected with SPECT, demonstrating feasibility of evaluation of the combination therapy with hNIS-expressing adenoviruses and radioiodide. 相似文献
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Kairemo Kalevi J. A. Ljunggren Kaj Wahlström Torsten Stigbrand Torgny Strand Sven-Erik 《Cell biochemistry and biophysics》1994,24(1-3):293-300
Tumor stroma contains much fibrin and monoclonal antifibrin antibody targeting is possible in tumors. In this study, nude
mouse human ovarian carcinoma xenograft specimens were investigated after treatment with90Y-labeled monoclonal antifibrin antibody Fab fragment or with90Y-labeled OC125-monoclonal antibody F(ab′)2 fragments. The mice received the radioimmunotherapy activity either intratumorally, intraperitoneally, or intravenously.
Beta-camera imaging (BCI) is a novel device for studying activity distribution in tissue specimens and, together with immunohistochemistry
(IHC) with OC125, antifibrin, anticarcinoembryonic antigen, anti-cytokeratin, and anti-placental alkaline phosphatase antibodies,
was used for correlation of activity distribution of tissue specimens. These results were in concordance: Antigen distribution
measured with IHC and radioactivity distribution were similar with the same antibodies, antifibrin, and OC125: However, these
antigens demonstrated rather different distribution. Tissue studies revealed that activity was concentrated also in the necrotic
tumor tissue, indicating that cell death was also caused by radiation. Differences in the tumor cell morphology were observed
using different routes of administration. With BCI, it is possible to quantitate activities in frozen sections (microdosimetry),
and these results were in concordance with absolute activities as measured by tissue sampling and well-counting. Three-dimensional
reconstruction of tissue slices combined with radioactivity distribution measured with BCI allows estimation of total absorbed
radiation dose in tumor after an appropriate dose planning. 相似文献
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Nestor M Persson M Cheng J Tolmachev V van Dongen G Anniko M Kairemo K 《Bioconjugate chemistry》2003,14(4):805-810
We have evaluated the applicability of the [(4-isothiocyanatobenzylammonio)undecahydro-closo-dodecaborate (1-)] (DABI) linker molecule for antibody radiohalogenation and compared it to radiohalogenation using the linker N-succinimidyl 4-iodobenzoate (PIB) and to direct radiohalogenation using Chloramine T. These studies were performed to assess the potential of DABI conjugates and to optimize the biological properties of halogen-labeled cMAb U36. The three conjugates were evaluated in vitro for their specificity and affinity and in vivo for their biodistribution patterns in normal mice at 1.5, 6, 24, and 96 h pi. Labeling efficiencies of direct CAT labeling, indirect PIB labeling, and indirect DABI labeling were 90-95%, 60%, and 68%, respectively. This resulted in a PIB:cMAb U36 molar ratio of 1.8-2.5 and a DABI:cMAb U36 molar ratio of 4.1. The in vitro data demonstrated specific binding for all conjugates and similar affinities with values around 1 x 10(8) M(-)(1). However, the in vivo data revealed accumulation of the radioiodine uptake in thyroid for the directly labeled conjugate, with a value 10 times higher than the indirectly labeled conjugates 96 h pi. Both the (125)I-PIB-cMAb U36 and (125)I-DABI-cMAb U36 conjugates yielded a low thyroid uptake with no accumulation, indicating different catabolites for these conjugates. This may favor the use of the indirectly labeled conjugates for future studies. Apart from the specific results obtained, these findings also demonstrate how the right linker molecule will provide additional opportunities to further improve the properties of an antibody-radionuclide conjugate. 相似文献
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The effects of daily 10-min mouse exposure tests on food consumption were studied in killer and non-killer Sprague-Dawley rats. The results showed both mouse-killers and non-killers significantly to decrease their food consumption when tested daily for mouse-killing. The effect was more pronounced in mouse-killers than in non-killers and the day-to-day individual fluctuation of food consumption was greater in mouse-killers during the mouse confrontation period. 相似文献
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