• Eur. J. Nucl. Med. Mol. Imaging · Nov 2003

    Comparative Study

    Reduction of 99mTc-sestamibi and 99mTc-tetrofosmin uptake in MRP-expressing breast cancer cells under hypoxic conditions is independent of MRP function.

    • Seigo Kinuya, Xiao-Feng Li, Kunihiko Yokoyama, Hirofumi Mori, Kazuhiro Shiba, Naoto Watanabe, Noriyuki Shuke, Hisashi Bunko, Takatoshi Michigishi, and Norihisa Tonami.
    • Department of Biotracer Medicine, Kanazawa University Graduate School of Medical Sciences, 13-1 Takaramachi, Kanazawa, Ishikawa 920-8640, Japan. kinuya@med.kanazawa-u.ac.jp
    • Eur. J. Nucl. Med. Mol. Imaging. 2003 Nov 1; 30 (11): 1529-31.

    AbstractHypoxia reduces the uptake of technetium-99m sestamibi (MIBI) in human cancer cell lines. In the current investigation, we attempted to identify the relationship between hypoxia-induced alteration of (99m)Tc-MIBI accumulation and expression of multi-drug resistance-associated protein (MRP) in the MCF7/WT breast cancer cell line and its subclonal cell line, MCF7/VP, which expresses high levels of MRP1. A second cationic compound, (99m)Tc-tetrofosmin (TF), was also examined. Cellular uptake of (99m)Tc-MIBI and (99m)Tc-TF was significantly higher in parental MCF7/WT cells than in MCF7/VP cells. Hypoxic conditions generated with a mixture of 95% N(2) and 5% CO(2) reduced cellular uptake of the two tracers in both parental MCF7/WT cells and MRP1-expressing MCF7/VP cells. Cell binding assay with iodine-125-labelled anti-MRP1 antibody demonstrated its specific binding to MCF7/VP cells. Hypoxia did not affect the amount of antibody bound to MCF7/VP cells. These results indicate that hypoxia-induced reduction of tracer uptake in tumour cells is a phenomenon independent of MRP function.

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