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99mTc-sestamibi to monitor treatment with antisense oligodeoxynucleotide complementary to MRP mRNA in human breast cancer cells

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Abstract

Objective

Technetium-99m sestamibi (MIBI) has been utilized to evaluate multi-drug resistance (MDR) phenomenon of malignant tumors and to predict chemotherapeutic effects on them. The current investigation examined the possibility of monitoring changes with respect to mRNA expression of multi-drug resistance associated protein (MRP) following antisense oligodeoxynucleotide (AS-ODN) treatment involving99mTc-MIBI.

Methods

The human breast cancer MCF-7 cell line and its MDR-induced MCF-7/VP cell line were employed. Cell suspensions of the two cell lines at 1 x 104 cells/m/ were inoculated in 24-well plates (0.2 ml/well) and incubated for one day. Antisense (AS) 20-mer phosphorothioate ODN complementary to the coding region of MRP mRNA and its sense (S) ODN were administered at final concentrations up to 25 μM, followed by a 5-day incubation.99mTc-MIBI solution was added to each well and incubated for 30 min. Cellular99mTc-MIBI uptake was corrected for protein concentration. MRP mRNA expression levels were analyzed via the reverse transcription Polymerase chain reaction (RT-PCR).

Results

Cellular uptake of99mTc-MIBI in MCF-7/VP cells was only 15% of that of MCF-7 cells. Following AS-ODN treatment at 25 μM for five days,99mTc-MIBI uptake in MCF-7/VP cells increased 2.4-fold in comparison with non-treated control cells.99mTc-MIBI uptake in MCF-7 cells was unaffected by AS-ODN administration. Sense ODN did not alter uptake in either cell line. RT-PCR confirmed reduction of MRP mRNA in MCF-7/VP cells following AS-ODN treatment.

Conclusion

Effects of AS-ODN administration on MRP function can be monitored via assessment of cellular uptake of99mTc-MIBI.

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Authors and Affiliations

  1. Department of Biotracer Medicine, Kanazawa University Graduate School of Medical Sciences, 13-1 Takaramachi, Kanazawa, 920-8640, Ishikawa, Japan

    Seigo Kinuya, Jingming Bai, Kunihiko Yokoyama, Makoto Fukuoka, Takatoshi Michigishi & Norihisa Tonami

  2. Radioisotope Center, Kanazawa University, 13-1 Takaramachi, Kanazawa, 920-8640, Ishikawa, Japan

    Kazuhiro Shiba & Hirofumi Mori

  3. Department of Radiology, Toyama Medical and Pharmaceutical University, Japan

    Naoto Watanabe

  4. Department of Radiology, Asahikawa Medical College, Japan

    Noriyuki Shuke

Authors
  1. Seigo Kinuya
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  2. Jingming Bai
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  3. Kazuhiro Shiba
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Correspondence to Seigo Kinuya.

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Kinuya, S., Bai, J., Shiba, K. et al. 99mTc-sestamibi to monitor treatment with antisense oligodeoxynucleotide complementary to MRP mRNA in human breast cancer cells. Ann Nucl Med 20, 29–34 (2006). https://doi.org/10.1007/BF02985587

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  • DOI: https://doi.org/10.1007/BF02985587

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