Biodistribution of the chimeric monoclonal antibody U36 radioiodinated with a closo-dodecaborate-containing linker: Comparison with other radioiodination methods
| العنوان: | Biodistribution of the chimeric monoclonal antibody U36 radioiodinated with a closo-dodecaborate-containing linker: Comparison with other radioiodination methods |
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| المؤلفون: | Nestor, Marika, Persson, Mikael, Cheng, Junping, Tolmachev, Vladimir, van Dongen, Guus, Anniko, Matti, Kairemo, Kalevi |
| المصدر: | Bioconjugate chemistry. 14(4):805-10 |
| مصطلحات موضوعية: | Animals, Antibodies, Monoclonal/administration & dosage/*chemistry/pharmacokinetics, Benzoates/chemistry/pharmacokinetics, Boron Compounds/*chemistry/pharmacokinetics, Cell Line, Tumor/radiation effects, Chloramines/chemistry/pharmacokinetics, Comparative Study, In Vitro, Iodine Radioisotopes/*chemistry/pharmacokinetics, Mice, Molecular Structure, Radiopharmaceuticals/*chemistry/pharmacokinetics, Research Support, Non-U.S. Gov't, Staining and Labeling/methods, Time Factors, Tissue Distribution, MEDICINE, MEDICIN |
| الوصف: | 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. |
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| الوصول الحر: | https://urn.kb.se/resolve?urn=urn:nbn:se:uu:diva-72824Test http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?db=PubMed&cmd=Retrieve&list_uids=12862434&dopt=CitationTest |
| قاعدة البيانات: | SwePub |
| تدمد: | 10431802 15204812 |
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| DOI: | 10.1021/bc034003n |