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Assessment of 99mTc-MIBI SPECT(/CT) to monitor multidrug resistance-related proteins and apoptosis-related proteins in patients with ovarian cancer: a preliminary study

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Abstract

Objective

Multidrug resistance (MDR) has been suggested to be a major cause of failure of chemotherapy treatment for cancer. It is associated with the expression of MDR-related and apoptosis-related proteins. Recently, technetium-99m hexakis 2-methoxyisobutylisonitrile (99mTc-MIBI) has been suggested as a tumor-seeking agent for the detection of MDR. The aim of this study was to evaluate 99mTc-MIBI single-photon emission computed tomography (SPECT)(/CT) for functional imaging of MDR-related and apoptosis-related proteins in patients with ovarian cancer.

Methods

Eleven women (mean age 63 years, range 53–76) with a clinical suspicion of ovarian cancer were prospectively studied. All patients were examined with 99mTc-MIBI imaging before surgery. After intravenous injection of 740 MBq 99mTc-MIBI, SPECT(/CT) imaging at 10 min and 2 h was performed. Based on the semiquantitative analysis of 99mTc-MIBI SPECT(/CT), both early and delayed tumor uptake ratios and washout rate % were calculated. The expression of MDR-related and apoptosis-related proteins was assessed in surgically excised tumors. Immunohistochemical staining was performed to quantify the expression levels of multidrug resistance protein 1 (MDR1), multidrug resistance-associated protein1 (MRP1), MRP3, lung resistance protein (LRP), breast cancer resistance protein (BCRP), Y-box-binding protein-1 (YB-1), Bcl-2, Bax and glutathione-S-transferase. 99mTc-MIBI imaging results and immunohistochemical results were compared.

Results

Laparotomy was performed in all patients. Six ovarian cancers were proven by histopathological examination. Five of the six ovarian cancers were positive for 99mTc-MIBI uptake on both early and delayed images with 99mTc-MIBI SPECT(/CT). MDR-related and apoptosis-related proteins were found to be expressed in all tumors. For the five positive 99mTc-MIBI uptake cases, the washout rate % of 99mTc-MIBI uptake showed a significant positive correlation with the expression of YB-1 (r = 0.988, P = 0.0015), and the early tumor uptake ratio showed a significant positive correlation with the expression of Bax (r = 0.882, P = 0.047).

Conclusions

Our results suggested that 99mTc-MIBI SPECT(/CT) might be a valuable diagnostic imaging technique to evaluate MDR-associated YB-1 and Bax-mediated apoptosis in patients with ovarian cancer.

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Acknowledgments

This study was supported by a Grant-in-Aid for Scientific Research, (C) 23591806, from the Ministry of Education. The authors thank the staff of the nuclear medicine imaging center at Kurume University Hospital for their skillful technical support. The authors thank Morio Ijichi, M. D., for help with our work.

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Authors and Affiliations

  1. Department of Radiology, Kurume University School of Medicine, 67 Asahi-Machi, Kurume, Fukuoka, 830-0011, Japan

    Seiji Kurata, Hayato Kaida, Yasumitsu Hirose, Masatoshi Ishibashi & Toshi Abe

  2. Department of Obstetrics and Gynecology, Kurume University School of Medicine, Kurume, Japan

    Kimio Ushijima & Kouichirou Kawano

  3. Department of Diagnostic Pathology, Kurume University Hospital, Kurume, Japan

    Akihiko Kawahara & Masayoshi Kage

  4. Department of Obstetrics and Gynecology, Yanagawa Hospital, Yanagawa, Japan

    Toshiharu Kamura

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  1. Seiji Kurata
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  2. Kimio Ushijima
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  3. Akihiko Kawahara
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  5. Kouichirou Kawano
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  9. Masatoshi Ishibashi
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Correspondence to Seiji Kurata.

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Kurata, S., Ushijima, K., Kawahara, A. et al. Assessment of 99mTc-MIBI SPECT(/CT) to monitor multidrug resistance-related proteins and apoptosis-related proteins in patients with ovarian cancer: a preliminary study. Ann Nucl Med 29, 643–649 (2015). https://doi.org/10.1007/s12149-015-0980-8

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  • DOI: https://doi.org/10.1007/s12149-015-0980-8

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