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Erschienen in: Annals of Nuclear Medicine 7/2015

01.08.2015 | Short Communication

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

verfasst von: Seiji Kurata, Kimio Ushijima, Akihiko Kawahara, Hayato Kaida, Kouichirou Kawano, Yasumitsu Hirose, Masayoshi Kage, Toshiharu Kamura, Masatoshi Ishibashi, Toshi Abe

Erschienen in: Annals of Nuclear Medicine | Ausgabe 7/2015

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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.
Literatur
1.
2.
Zurück zum Zitat Bookman MA. First-line chemotherapy in epithelial ovarian cancer. Clin Obstet Gynecol. 2012;55:96–113.PubMedCrossRef Bookman MA. First-line chemotherapy in epithelial ovarian cancer. Clin Obstet Gynecol. 2012;55:96–113.PubMedCrossRef
3.
Zurück zum Zitat Johnatty SE, Beesley J, Paul J, Fereday S, Spurdle AB, Webb PM, et al. ABCB1 (MDR 1) polymorphisms and progression-free survival among women with ovarian cancer following paclitaxel/carboplatin chemotherapy. Clin Cancer Res. 2008;14:5594–601.PubMedCrossRef Johnatty SE, Beesley J, Paul J, Fereday S, Spurdle AB, Webb PM, et al. ABCB1 (MDR 1) polymorphisms and progression-free survival among women with ovarian cancer following paclitaxel/carboplatin chemotherapy. Clin Cancer Res. 2008;14:5594–601.PubMedCrossRef
4.
Zurück zum Zitat Higgins CF. ABC transporters: from microorganisms to man. Annu Rev Cell Biol. 1992;8:67–113.PubMedCrossRef Higgins CF. ABC transporters: from microorganisms to man. Annu Rev Cell Biol. 1992;8:67–113.PubMedCrossRef
5.
Zurück zum Zitat Tamaki A, Ierano C, Szakacs G, Robey RW, Bates SE. The controversial role of ABC transporters in clinical oncology. Essays Biochem. 2011;50:209–32.PubMedCrossRef Tamaki A, Ierano C, Szakacs G, Robey RW, Bates SE. The controversial role of ABC transporters in clinical oncology. Essays Biochem. 2011;50:209–32.PubMedCrossRef
6.
Zurück zum Zitat Rothnie A, Callaghan R, Deeley RG, Cole SP. Role of GSH in estrone sulfate binding and translocation by the multidrug resistance protein 1 (MRP1/ABCC1). J Biol Chem. 2006;281:13906–14.PubMedCrossRef Rothnie A, Callaghan R, Deeley RG, Cole SP. Role of GSH in estrone sulfate binding and translocation by the multidrug resistance protein 1 (MRP1/ABCC1). J Biol Chem. 2006;281:13906–14.PubMedCrossRef
7.
Zurück zum Zitat Kamura T, Yahata H, Amada S, Ogawa S, Sonoda T, Kobayashi H, et al. Is nuclear expression of Y box-binding protein-1 a new prognostic factor in ovarian serous adenocarcinoma? Cancer. 1999;85:2450–4.PubMedCrossRef Kamura T, Yahata H, Amada S, Ogawa S, Sonoda T, Kobayashi H, et al. Is nuclear expression of Y box-binding protein-1 a new prognostic factor in ovarian serous adenocarcinoma? Cancer. 1999;85:2450–4.PubMedCrossRef
8.
Zurück zum Zitat Huang X, Ushijima K, Komai K, Takemoto Y, Motoshima S, Kamura T, et al. Co-expression of Y box-binding protein-1 and P-glycoprotein as a prognostic marker for survival in epithelial ovarian cancer. Gynecol Oncol. 2004;93:287–91.PubMedCrossRef Huang X, Ushijima K, Komai K, Takemoto Y, Motoshima S, Kamura T, et al. Co-expression of Y box-binding protein-1 and P-glycoprotein as a prognostic marker for survival in epithelial ovarian cancer. Gynecol Oncol. 2004;93:287–91.PubMedCrossRef
9.
Zurück zum Zitat Arts HJ, Katsaros D, de Vries EG, Massobrio M, Genta F, Danese S, et al. Drug resistance-associated markers P-glycoprotein, multidrug resistance-associated protein 1, multidrug resistance-associated protein 2, and lung resistance protein as prognostic factors in ovarian carcinoma. Clin Cancer Res. 1999;5:2798–805.PubMed Arts HJ, Katsaros D, de Vries EG, Massobrio M, Genta F, Danese S, et al. Drug resistance-associated markers P-glycoprotein, multidrug resistance-associated protein 1, multidrug resistance-associated protein 2, and lung resistance protein as prognostic factors in ovarian carcinoma. Clin Cancer Res. 1999;5:2798–805.PubMed
10.
Zurück zum Zitat Mubashar M, Harrington KJ, Chaudhary KS, Lalani EL-N, Stamp GW, Sinnett D, et al. 99mTc-sestamibi imaging in the assessment of toremifene as a modulator of multidrug resistance in patients with breast cancer. J Nucl Med. 2002;43:519–25.PubMed Mubashar M, Harrington KJ, Chaudhary KS, Lalani EL-N, Stamp GW, Sinnett D, et al. 99mTc-sestamibi imaging in the assessment of toremifene as a modulator of multidrug resistance in patients with breast cancer. J Nucl Med. 2002;43:519–25.PubMed
11.
Zurück zum Zitat Duan XY, Wang JS, Liu M, Guo YM. Technetium-99m-hexakis-2-methoxyisobutylisonitrile scintigraphy and multidrug resistance-related protein expression in human primary lung cancer. Ann Nucl Med. 2008;22:49–55.PubMedCrossRef Duan XY, Wang JS, Liu M, Guo YM. Technetium-99m-hexakis-2-methoxyisobutylisonitrile scintigraphy and multidrug resistance-related protein expression in human primary lung cancer. Ann Nucl Med. 2008;22:49–55.PubMedCrossRef
12.
Zurück zum Zitat Saggiorato E, Angusti T, Rosas R, Martinese M, Finessi M, Arecco F, et al. 99mTc-MIBI Imaging in the presurgical characterization of thyroid follicular neoplasms: relationship to multidrug resistance protein expression. J Nucl Med. 2009;50:1785–93.PubMedCrossRef Saggiorato E, Angusti T, Rosas R, Martinese M, Finessi M, Arecco F, et al. 99mTc-MIBI Imaging in the presurgical characterization of thyroid follicular neoplasms: relationship to multidrug resistance protein expression. J Nucl Med. 2009;50:1785–93.PubMedCrossRef
13.
Zurück zum Zitat Wang XS, Zhang YJ, Liu XL, Zhou ZR, Hu CS, Eisbruch A. The role of technetium-99m methoxyisobutyl isonitrile scintigraphy in predicting the therapeutic effect of chemotherapy against nasopharyngeal carcinoma. Cancer. 2011;117:2435–41.PubMedCrossRef Wang XS, Zhang YJ, Liu XL, Zhou ZR, Hu CS, Eisbruch A. The role of technetium-99m methoxyisobutyl isonitrile scintigraphy in predicting the therapeutic effect of chemotherapy against nasopharyngeal carcinoma. Cancer. 2011;117:2435–41.PubMedCrossRef
14.
Zurück zum Zitat Piwnica-Worms D, Chiu ML, Budding M, Kronauge JF, Kramer RA, Croop JM. Functional imaging of multidrug-resistant P-glycoprotein with an organotechnetium complex. Cancer Res. 1993;53:977–84.PubMed Piwnica-Worms D, Chiu ML, Budding M, Kronauge JF, Kramer RA, Croop JM. Functional imaging of multidrug-resistant P-glycoprotein with an organotechnetium complex. Cancer Res. 1993;53:977–84.PubMed
15.
Zurück zum Zitat Cory S, Adams JM. The Bcl2 family: regulators of the cellular life-or-death switch. Nat Rev Cancer. 2002;2:647–56.PubMedCrossRef Cory S, Adams JM. The Bcl2 family: regulators of the cellular life-or-death switch. Nat Rev Cancer. 2002;2:647–56.PubMedCrossRef
16.
Zurück zum Zitat Del Vecchio S, Zannetti A, Aloj L, Caracò C, Ciarmiello A, Salvatore M. Inhibition of early 99mTc-MIBI uptake by Bcl-2 anti-apoptotic protein overexpression in untreated breast carcinoma. Eur J Nucl Med Mol Imaging. 2003;30:879–87.PubMedCrossRef Del Vecchio S, Zannetti A, Aloj L, Caracò C, Ciarmiello A, Salvatore M. Inhibition of early 99mTc-MIBI uptake by Bcl-2 anti-apoptotic protein overexpression in untreated breast carcinoma. Eur J Nucl Med Mol Imaging. 2003;30:879–87.PubMedCrossRef
17.
Zurück zum Zitat Kawahara A, Hattori S, Akiba J, Nakashima K, Taira T, Watari K, et al. Infiltration of thymidine phosphorylase-positive macrophages is closely associated with tumor angiogenesis and survival in intestinal type gastric cancer. Oncol Rep. 2010;24:405–15.PubMedCrossRef Kawahara A, Hattori S, Akiba J, Nakashima K, Taira T, Watari K, et al. Infiltration of thymidine phosphorylase-positive macrophages is closely associated with tumor angiogenesis and survival in intestinal type gastric cancer. Oncol Rep. 2010;24:405–15.PubMedCrossRef
18.
Zurück zum Zitat Stelmachów J, Timorek-Lemieszczuk A. Technetium-99m-sestamibi scintigraphy in gynecological cancer imaging. Eur J Gynaecol Oncol. 2008;29:309–12.PubMed Stelmachów J, Timorek-Lemieszczuk A. Technetium-99m-sestamibi scintigraphy in gynecological cancer imaging. Eur J Gynaecol Oncol. 2008;29:309–12.PubMed
19.
Zurück zum Zitat Lasham A, Print CG, Woolley AG, Dunn SE, Braithwaite AW. YB-1: oncoprotein, prognostic marker and therapeutic target? Biochem J. 2013;449:11–23.PubMedCrossRef Lasham A, Print CG, Woolley AG, Dunn SE, Braithwaite AW. YB-1: oncoprotein, prognostic marker and therapeutic target? Biochem J. 2013;449:11–23.PubMedCrossRef
20.
Zurück zum Zitat Yang A, Xue J, Li X, Yu Y, Deng H, Hu G, et al. Experimental and clinical observations of 99mTc-MIBI uptake correlate with P-glycoprotein expression in lung cancer. Nucl Med Commun. 2007;28:696–703.PubMedCrossRef Yang A, Xue J, Li X, Yu Y, Deng H, Hu G, et al. Experimental and clinical observations of 99mTc-MIBI uptake correlate with P-glycoprotein expression in lung cancer. Nucl Med Commun. 2007;28:696–703.PubMedCrossRef
21.
Zurück zum Zitat Saji H, Toi M, Saji S, Koike M, Kohno K, Kuwano M. Nuclear expression of YB-1 protein correlates with P-glycoprotein expression in human breast carcinoma. Cancer Lett. 2003;190:191–7.PubMedCrossRef Saji H, Toi M, Saji S, Koike M, Kohno K, Kuwano M. Nuclear expression of YB-1 protein correlates with P-glycoprotein expression in human breast carcinoma. Cancer Lett. 2003;190:191–7.PubMedCrossRef
22.
Zurück zum Zitat Arao S, Suwa H, Mandai M, Tashiro H, Miyazaki K, Okamura H, et al. Expression of multidrug resistance gene and localization of P-glycoprotein in human primary ovarian cancer. Cancer Res. 1994;54:1355–9.PubMed Arao S, Suwa H, Mandai M, Tashiro H, Miyazaki K, Okamura H, et al. Expression of multidrug resistance gene and localization of P-glycoprotein in human primary ovarian cancer. Cancer Res. 1994;54:1355–9.PubMed
23.
Zurück zum Zitat Kostakoglu L, Kiratli P, Ruacan S, Hayran M, Emri S, Ergün EL. Association of tumor washout rates and accumulation of technetium-99m-MIBI with expression of P-glycoprotein in lung cancer. J Nucl Med. 1998;39:228–34.PubMed Kostakoglu L, Kiratli P, Ruacan S, Hayran M, Emri S, Ergün EL. Association of tumor washout rates and accumulation of technetium-99m-MIBI with expression of P-glycoprotein in lung cancer. J Nucl Med. 1998;39:228–34.PubMed
24.
Zurück zum Zitat Moretti JL, Hauet N, Caglar M, Rebillard O, Burak Z. To use MIBI or not to use MIBI? That is the question when assessing tumour cells. Eur J Nucl Med Mol Imaging. 2005;32:836–42.PubMedCrossRef Moretti JL, Hauet N, Caglar M, Rebillard O, Burak Z. To use MIBI or not to use MIBI? That is the question when assessing tumour cells. Eur J Nucl Med Mol Imaging. 2005;32:836–42.PubMedCrossRef
Metadaten
Titel
Assessment of 99mTc-MIBI SPECT(/CT) to monitor multidrug resistance-related proteins and apoptosis-related proteins in patients with ovarian cancer: a preliminary study
verfasst von
Seiji Kurata
Kimio Ushijima
Akihiko Kawahara
Hayato Kaida
Kouichirou Kawano
Yasumitsu Hirose
Masayoshi Kage
Toshiharu Kamura
Masatoshi Ishibashi
Toshi Abe
Publikationsdatum
01.08.2015
Verlag
Springer Japan
Erschienen in
Annals of Nuclear Medicine / Ausgabe 7/2015
Print ISSN: 0914-7187
Elektronische ISSN: 1864-6433
DOI
https://doi.org/10.1007/s12149-015-0980-8

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