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Enhancing the effect of radionuclide tumor targeting, using lysosomotropic weak bases
Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Oncology, Radiology and Clinical Immunology, Biomedical Radiation Sciences.
Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Oncology, Radiology and Clinical Immunology, Biomedical Radiation Sciences.
2007 (English)In: International Journal of Radiation Oncology, Biology, Physics, ISSN 0360-3016, Vol. 67, no 1, 279-287 p.Article in journal (Refereed) Published
Abstract [en]

PURPOSE: The aim of the present study was to investigate if treatment with lysosomotropic weak bases could increase the intracellular retention of radiohalogens and thereby increase the therapeutic effect of radionuclide tumor targeting. METHODS AND MATERIALS: Four different lysosomotropic bases, chloroquine, ammonium chloride, amantadine, and thioridazine, were investigated for their ability to increase radiohalogen retention in vitro. The two most promising substances, chloroquine and ammonium chloride, were studied in several cell lines (A431, U343MGaCl2:6, SKOV-3, and SKBR-3) in combination with radiolabeled epidermal growth factor (EGF) or the HER2 binding affibody (Z(HER2:4))(2). RESULTS: The uptake and retention of radionuclides was found to be substantially increased by simultaneous treatment with the lysosomotropic bases. The effect was, however, more pronounced in the epidermal growth factor:epidermal growth factor receptor (EGF:EGFR) system than in the (Z(HER2:4))(2):HER2 system. The therapeutic effect of ammonium chloride treatment combined with (211)At-EGF was also studied. The effect obtained after combined treatment was found to be much better than after (211)At-EGF treatment alone. CONCLUSIONS: The encouraging results from the present study indicate that the use of lysosomotropic weak bases is a promising approach for increasing the therapeutic effect of radionuclide targeting with radiohalogens.

Place, publisher, year, edition, pages
2007. Vol. 67, no 1, 279-287 p.
Keyword [en]
EGF, HER2, Lysosomotropic weak bases, Radionuclide therapy, Tumor targeting
National Category
Medical and Health Sciences
Identifiers
URN: urn:nbn:se:uu:diva-104625DOI: 10.1016/j.ijrobp.2006.07.1369ISI: 000243292000040PubMedID: 17189076OAI: oai:DiVA.org:uu-104625DiVA: diva2:220028
Available from: 2009-05-29 Created: 2009-05-29 Last updated: 2011-02-17Bibliographically approved

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