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Clinical Cancer Research Vol. 10, 3788-3793, June 1, 2004
© 2004 American Association for Cancer Research

Molecular Oncology, Markers, Clinical Correlates

Usefulness of 99mTc-Sestamibi Scintigraphy in Suggesting the Therapeutic Effect of Chemotherapy against Gastric Cancer

Kenji Kawata, Michiyuki Kanai, Tetsuro Sasada, Shingo Iwata, Naritaka Yamamoto and Arimichi Takabayashi

Department of Surgery, Tazuke-Kofukai Medical Research Institute and Kitano Hospital, Osaka, Japan


   ABSTRACT
Top
 ABSTRACT
INTRODUCTION
 PATIENTS AND METHODS
 RESULTS
 DISCUSSION
 REFERENCES
 
Purpose: Imaging with 99mTc-sestamibi (99mTc-MIBI) has been used to assess 170-kDa P-glycoprotein (P-gp) expression and predict chemotherapy responses in several types of malignancy, such as breast and lung cancers. The purpose of this study was to evaluate the relationship between 99mTc-MIBI accumulation in tumors and sensitivity to chemotherapy in gastric cancer patients.

Experimental Design: Thirty-six patients with advanced gastric cancer underwent 99mTc-MIBI scintigraphy before chemotherapy. Patients also underwent endoscopic biopsy, and the expression of P-gp or multidrug resistance-associated protein was analyzed by immunohistochemical staining. The relationship between the accumulation of 99mTc-MIBI in tumors and responses to chemotherapy with 5-fluorouracil/cis-diamminedichloroplatinum(II) or epirubicin was examined.

Results: Higher accumulation of 9mTc-MIBI in tumors was observed in 25 and 23 of 36 gastric cancer patients at the early (30 min) and delayed (120 min) images, respectively. Accelerated accumulation of 99mTc-MIBI negatively correlates with increased expression of P-gp, but not of multidrug resistance-associated protein, as determined by immunohistochemistry in gastric cancer tissues. The response rate to 5-fluorouracil/cis-diamminedichloroplatinum(II) chemotherapy in patients with high 99mTc-MIBI accumulation (15.4%) was much lower than that in patients with low 99mTc-MIBI accumulation (54.5%). In contrast, patients with high 99mTc-MIBI accumulation show a higher response rate (41.7%) to chemotherapy with epirubicin, which is known to be a substrate of P-gp transporter.

Conclusions: 99mTc-MIBI scintigraphy is useful to suggest the responses to chemotherapy of patients with advanced gastric cancer.


   INTRODUCTION
Top
 ABSTRACT
 INTRODUCTION
PATIENTS AND METHODS
 RESULTS
 DISCUSSION
 REFERENCES
 
Multidrug resistance is the major barrier to efficient chemotherapy of cancer. Causes of chemotherapy failure are multifactorial, including the physical inability of drugs to reach malignant cells because of poor tumor vascularization and diverse cellular mechanisms lowering intracellular drug concentration or altering the ability of the drugs to affect their targets (1) . One of the cellular mechanisms of multidrug resistance involves 170-kDa P-glycoprotein (P-gp), which acts as an ATP-dependent efflux pump for several anticancer agents (2) .

99mTc-Sestamibi (99mTc-MIBI), a lipophilic cation originally developed for scintigraphic evaluation of coronary blood flow (3 , 4) , has been used for imaging of tumors originating from multiple organs, such as the parathyroid gland (5) , brain (6) , lung (7 , 8) , breast (9) , and thyroid gland (10) . Because 99mTc-MIBI is passively taken up into the mitochondria in metabolically active tumor cells and exported from cells by P-gp (11 , 12) , this imaging procedure has been also applied to detect functional P-gp expression and to predict sensitivity of cancer cells to chemotherapy in some types of cancers (13, 14, 15, 16, 17, 18, 19) . Significant correlations have been reported between 99mTc-MIBI scintigraphy and P-gp immunohistochemistry, in vitro cytotoxicity assay, chemotherapy response, and/or patient outcome in several types of malignancy, including breast cancer (13) , lung cancer (14, 15, 16) , hepatocellular carcinoma (17) , malignant lymphoma (18) , soft tissue sarcoma, and bone sarcoma (19) . Although P-gp expression can be evaluated by other methods, such as immunohistochemistry and Western or Northern blotting, in tumor tissues available from diagnostic biopsy, the results from these methods may not represent entire tumors but only small portions of large and heterogeneous tumors. In contrast, imaging with 99mTc-MIBI can evaluate entire tumors and may provide a number of advantages to assess P-gp expression and predict chemotherapy responses. Of note, it can be performed noninvasively, allowing for sequential evaluation of P-gp expression and function through repeated assessment at different time points.

Although some investigators have reported the usefulness of 99mTc-MIBI imaging in several types of cancers (13, 14, 15, 16, 17, 18, 19) , others have suggested conflicting results that 99mTc-MIBI imaging did not correlate with measures of P-gp expression or chemotherapy responses in some tumors (20, 21, 22) . Because the relationship between the extent of 99mTc-MIBI accumulation and chemotherapy responses has not been addressed in gastric cancer, we performed 99mTc-MIBI scintigraphy in patients with advanced gastric cancer. In the present study, we evaluated whether the results of 99mTc-MIBI scintigraphy correlate with the chemotherapeutic effects and provide useful information to select chemotherapy regimens in gastric cancer.


   PATIENTS AND METHODS
Top
 ABSTRACT
 INTRODUCTION
 PATIENTS AND METHODS
RESULTS
 DISCUSSION
 REFERENCES
 
Patient Population.
Thirty-six patients with advanced gastric cancer who underwent 99mTc-MIBI scintigraphy before chemotherapy were studied (Table 1)Citation . No patients had ischemic heart disease. Patients consisted of 25 men and 11 women (age, 24–79 years; mean age, 64.5 years). Clinical examination revealed intestinal-type gastric cancer in 17 patients and diffuse-type gastric cancer in 19 patients. Clinical staging before chemotherapy showed that 11 patients had stage III disease, and 25 patients had stage IV disease. The patients were divided into two groups by the treatment given. Twenty-four patients received three cycles of a combined 5-fluorouracil (5-FU)/cis-diamminedichloroplatinum(II) (CDDP) therapy, and each cycle consisted of a continuous infusion of 5-FU at 500 mg/m2/day for 7 days and a bolus infusion of CDDP at 7.5 mg/m2/day for 5 days in a row. Twelve patients were given a bolus infusion of epirubicin at 30 mg/m2/week, two or three times.


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  		Table 1 Patient characteristics

 
99mTc-MIBI Scintigraphy.
The instrument used was Starcom 4000 (General Electric Company) connected with a low-energy high-resolution collimator (collection energy, 140 KeV; window width, 20%). Early and delayed images were acquired at 30 and 120 min after i.v. injection of 600 MBq 99mTc-MIBI, respectively. A representative case is shown in Fig. 1Citation . For quantitative evaluation, the regions of interest were placed over the gastric lesion and the heart. The count per pixel for each region of interest was determined, and then early uptake ratio (ER) and delayed uptake ratio (DR) were calculated by dividing the lesion count by the heart count obtained from the early and delayed images, respectively. Accumulation of 99mTc-MIBI was considered high when the patients showed either high ER (>=1.00) or high DR (>=0.75) and low when patients showed both low ER (<1.00) and low DR (<0.75).



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  		Fig. 1. 99mTc-Sestamibi (99mTc-MIBI) scintigraphy in a gastric cancer patient. Endoscopy (A), upper gastrointestinal series (B), and 99mTc-MIBI scintigraphy (C) in a gastric cancer patient are shown. Arrowheads represent the 99mTc-MIBI accumulation in the gastric lesion (closed arrowhead) and the heart (open arrowhead).

 
Immunohistochemical Analysis.
All patients underwent endoscopic biopsy before chemotherapy. The expression of P-gp or multidrug resistance-associated protein (MRP) was analyzed in paraffin-embedded specimens by immunohistochemical staining with anti-P-gp monoclonal antibody (UIC2; Beckman Instruments Inc., Fullerton, CA) or anti-MRP monoclonal antibody (MRPm6; MONOSAN, Uden, the Netherlands). Tumors were classified as positive when >50% of cells were stained and negative when <50% of cells were stained (Fig. 2)Citation .



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  		Fig. 2. Immunohistochemical analysis of the expression of 170-kDa P-glycoprotein in gastric cancer tissues. The expression of 170-kDa P-glycoprotein was analyzed immunohistochemically. Tumors were classified as positive when >50% of cells were stained (A) and negative when <50% were stained (B).

 
Evaluation of Therapeutic Effects and Statistical Analysis.
Therapeutic effects were evaluated according to the clinical and histological criteria described in Japanese Classification of Gastric Carcinoma (23) . Values are expressed as mean ± SD. Statistical analysis was performed with the Fisher’s exact test for nominal data and Mann-Whitney test for numerical data, using a statistical analysis program (StatView 5.0 software; Abacus Concepts, Inc., Berkeley, CA), and differences at P < 0.05 were considered as significant.


   RESULTS
Top
 ABSTRACT
 INTRODUCTION
 PATIENTS AND METHODS
 RESULTS
DISCUSSION
 REFERENCES
 
99mTc-MIBI Accumulation in Gastric Cancer.
There have been an increasing number of studies describing 99mTc-MIBI accumulation in tumors, including tumors of the parathyroid gland (5) , brain (6) , lung (7 , 8) , breast (9) , and thyroid gland (10) . To know whether 99mTc-MIBI can also accumulate in gastric cancer tissues, we quantitatively evaluated the ER and DR from the early (30 min) and delayed (120 min) images after i.v. injection of 99mTc-MIBI in 36 gastric cancer patients. As shown in Fig. 1Citation , 99mTc-MIBI was strongly accumulated in the gastric cancer tissue in some of patients. According to the quantitative evaluation, higher accumulation of 99mTc-MIBI in tumors was observed in 25 and 23 of 36 gastric cancer patients in the early (30 min) and delayed (120 min) images, respectively.

Higher Uptake of 99mTc-MIBI Correlates with the Decrease in P-gp Expression in Gastric Cancer Tissues.
99mTc-MIBI has been known to be a suitable transport substrate of P-gp and/or MRP (21, 22, 23, 24) . In some cancer cell lines or cancer tissues, reduced ability to accumulate 99mTc-MIBI has been reported to correlate well with increased expression of P-gp and/or MRP. Therefore, we determined the expressions of P-gp or MRP in gastric cancer tissues by immunohistochemical staining and compared their levels with the degree of 99mTc-MIBI accumulation. The expression of P-gp in cancer tissues was positive in 9 patients and negative in 19 patients. As shown in Table 2Citation , both ER and DR of 99mTc-MIBI were significantly lower in P-gp-positive cases than in P-gp-negative cases, suggesting that the accumulation of 99mTc-MIBI in gastric cancer tissues may be dependent, at least in part, on the expression level of P-gp. In contrast, the expression of MRP was positive in 11 patients and negative in 17 patients, but there was no significant correlation between expression of MRP and 99mTc-MIBI accumulation in gastric cancer tissues (Table 2)Citation . Although the data are not shown, there was no significant correlation between histology and 99mTc-MIBI accumulation: ER was 0.97 ± 0.35 in intestinal type (n = 17) versus 1.11 ± 0.55 in diffuse type (n = 19); and DR was 0.82 ± 0.29 in intestinal type (n = 17) versus 0.89 ± 0.60 in diffuse type (n = 19).


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  		Table 2 Relationship between 99mTc-MIBIa accumulation and P-gp or MRP expression

 
5-FU/CDDP Chemotherapy Was Effective in Patients with Lower 99mTc-MIBI Accumulation.
The response rate was 33.3% in 24 patients who underwent conventional chemotherapy with 5-FU and CDDP: complete response in 0 patients; partial response in 8 patients; no change (NC) in 16 patients; and progressive disease partial response in 0 patients. We evaluated the relationship between 99mTc-MIBI accumulation in tumors and responses to this chemotherapeutic regimen in these patients. As shown in Table 3Citation , the response rate to 5-FU/CDDP chemotherapy in patients with high 99mTc-MIBI accumulation who showed either high ER (>=1.00) or high DR (>=0.75) was much lower than that in patients with low 99mTc-MIBI accumulation who showed both low ER (<1.00) and low DR (<0.75) [15.4% versus 54.5%]. In particular, the response rate of the patients whose ER was >1.20 was 0% (NC in 11 patients). In addition, both ER and DR tend to be lower in 8 cases with partial response than in 16 cases with NC [ER = 0.79 ± 0.31 in partial response cases versus 1.26 ± 0.77 in cases with NC (P = 0.22); DR = 0.66 ± 0.22 in cases with partial response versus 0.88 ± 0.54 in cases with NC (P = 0.32)], although the differences are not statistically significant (Table 4)Citation . These results suggested that patients with lower 99mTc-MIBI accumulation show higher sensitivity to chemotherapy with 5-FU/CDDP, compared with patients with higher 99mTc-MIBI accumulation.


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  		Table 3 99mTc-MIBIa accumulation and therapeutic responses to chemotherapy with combined 5-FU/CDDP or epirubicin in advanced gastric cancer patients

 

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  		Table 4 Relationship between responsiveness to the combined 5-FUa/CDDP therapy and 99mTc-MIBI accumulation

 
Chemotherapy with Epirubicin Was Effective in Patients with Higher 99mTc-MIBI Accumulation.
As shown in Table 2Citation , the accelerated accumulation of 99mTc-MIBI in gastric cancer tissues might be associated with a lower expression or absence of P-gp, which has been shown to export several anticancer drugs, such as anthracyclines, Vinca alkaloids, and actinomycin D, out of cells (2) . Because patients with higher 99mTc-MIBI accumulation were not sensitive to the combined 5-FU/CDDP therapy, we tried another regimen with epirubicin, which is a substrate of P-gp, in 12 patients who showed either high ER (>=1.00) or DR (>=0.75). As shown in Table 3Citation , the response rate to chemotherapy with epirubicin (41.7%) was much higher than that to the conventional chemotherapy with 5-FU/CDDP (15.4%) in patients with high accumulation of 99mTc-MIBI.

Fig. 3Citation shows the case of a 30-year-old male patient with high accumulation of 99mTc-MIBI, who was successfully treated with epirubicin. He was diagnosed with a diffuse type of gastric cancer spreading from the cardia to the angle of the stomach by a series of examinations including upper gastrointestinal series (Fig. 3A)Citation , endoscopy (Fig. 3B)Citation , and computed tomography (Fig. 3C)Citation . Because 99mTc-MIBI scintigraphy showed high accumulation in the gastric tumor (Fig. 3D)Citation , he was treated with a bolus infusion of epirubicin (40 mg/m2/week) three times. After chemotherapy with epirubicin, the gastric tumor was remarkably reduced in size, and both mucosal irregularity and restricted wall distension were drastically improved (Fig. 3, E–G)Citation . The 99mTc-MIBI scintigraphy performed again after chemotherapy showed a remarkable reduction in 99mTc-MIBI accumulation in the gastric lesion (Fig. 3H)Citation .



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  		Fig. 3. Epirubicin was effective in an advanced gastric cancer patient with high 99mTc-sestamibi accumulation. Upper gastrointestinal series (A and E), endoscopy (B and F), computed tomography (C and G), and 99mTc-sestamibi scintigraphy (D and H) are shown in a patient with highly advanced gastric cancer before (A–D) and after (E–H) chemotherapy with epirubicin.

 

   DISCUSSION
Top
 ABSTRACT
 INTRODUCTION
 PATIENTS AND METHODS
 RESULTS
 DISCUSSION
REFERENCES
 
It is well known that tumor cells that have become resistant to one type of anticancer drug acquire cross-resistance to other anticancer drugs with completely different structures. This phenomenon is called multidrug resistance, which is a major obstacle to treatment of cancer patients in the clinic. One of the important mechanisms resulting in multidrug resistance is the increased expression and/or function of cellular membrane proteins, such as P-gp and MRP, which can export anticancer drugs from cancer cells (1) . Different types of drugs, including doxorubicin, epirubicin, actinomycin D, mitomycin C, and vinblastine, have been known to be substrates of a cell surface P-gp transporter (2) . Previous studies have reported a significant correlations between 99mTc-MIBI accumulation and P-gp expression in immunohistochemistry in several types of cancer (13, 14, 15, 16, 17, 18, 19) . In addition, Piwnica-Worms et al. (24) have demonstrated that the uptake of 99mTc-MIBI is increased about 10 times in cells with low expression of P-gp and about 200 times in those with abundant P-gp after administration of drugs that can inhibit the activity of P-gp, such as verapamil and cyclosporin. These findings strongly indicate that 99mTc-MIBI is a suitable substrate of P-gp. In the present study, we also showed a significant correlation between P-gp expression and the extent of 99mTc-MIBI accumulation determined by both ER and DR in gastric tumors. Consistent with studies in other types of cancers (13, 14, 15, 16, 17, 18, 19) , our finding suggests that the accumulation of 99mTc-MIBI in gastric cancer tissues may be dependent, at least in part, on the expression level of P-gp. Several methods, such as Northern or Western blotting and immunohistochemistry, have been used to evaluate P-gp expression in human tissues. However, the results of these methods cannot always represent all tumor characteristics because most specimens are obtained from small parts of heterogeneous and large tumors and may not be good representatives for evaluating tumor characteristics. In contrast, 99mTc-MIBI imaging can evaluate the entire tumor noninvasively, allowing for repeated assessments, and might have a number of theoretical advantages for the assessment of P-gp expression.

It has been suggested that MRP also affects the accumulation of 99mTc-MIBI in some types of cancer (25, 26, 27) , but our study could not demonstrate any correlation between MRP expression and ER or DR in 99mTc-MIBI imaging in gastric cancer. Similar to our finding, previous studies reported that an increased expression of P-gp, but not of MRP, correlates with low accumulation of 99mTc-MIBI in some types of malignancy, such as lung cancer (28) and hepatocellular carcinoma (29) . Moretti et al. (26) have shown that MRP-dependent 99mTc-MIBI efflux from cancer cells is highly dependent on intracellular glutathione concentration in cancer cell lines. Although further study is needed, intracellular glutathione or unknown other factors may be involved in the mechanism of 99mTc-MIBI export by MRP in gastric cancer cells.

In terms of the correlation between the chemotherapeutic effect and 99mTc-MIBI accumulation, several studies have shown that chemotherapy with doxorubicin, one of the substrates of P-gp, is more effective in patients with higher 99mTc-MIBI accumulation in lung cancer (14, 15, 16) , breast cancer (13) , and bone and soft tissue tumors (19) . Consistent with these previous reports, the present study has demonstrated that gastric cancer patients with accelerated 99mTc-MIBI accumulation show a higher sensitivity to epirubicin, another anthracycline derivative structurally similar to doxorubicin. Of note, we have also shown that gastric cancer patients with lower 99mTc-MIBI accumulation have a higher sensitivity to 5-FU/CDDP therapy, although we de not know the molecular mechanism behind this unexpected result. Besides P-gp or MRP expression in tumor tissues, 99mTc-MIBI accumulation in tumors has been reported to be affected by a number of factors, including blood flow, tissue viability, vascular permeability, tumor necrosis, metabolic demand, and mitochondrial activity of the tumor (30) . Thus, some factors may be responsible for higher chemotherapeutic responses to 5-FU/CDDP therapy in patients with lower 99mTc-MIBI accumulation.

Although we need additional studies with an extended number of patients to confirm the accuracy of our findings, the present study suggests the usefulness of the determination of 99mTc-MIBI accumulation in tumors to predict the therapeutic effect of chemotherapy in gastric cancer patients. In our pilot study, the response rates to epirubicin and 5-FU/CDDP in patients with high and low 99mTc-MIBI accumulation were 41.7% and 54.5%, respectively. These response rates are very close to those reported in the most promising and standard chemotherapy regimen currently available in advanced gastric cancer, a combination of epirubicin, CDDP, and 5-FU, which causes more severe adverse effects (31 , 32) . Therefore, 99mTc-MIBI imaging seems to be beneficial for selecting a more effective and less toxic chemotherapy protocol for individual patients by suggesting response or resistance to each of chemotherapeutic drug. It might also have diagnostic utility and potential therapeutic implications to help determine whether the accumulation of 99mTc-MIBI can be modulated in tumors through administration of drugs to inhibit P-gp activity, such as PSC833 (33 , 34) . In addition, evaluations at different time points or changes in the scans obtained for sequential evaluation may be useful for selecting the most appropriate chemotherapy protocol because the sensitivity of tumors to chemotherapeutic drugs may change frequently during treatment.


   FOOTNOTES
 
The costs of publication of this article were defrayed in part by the payment of page charges. This article must therefore be hereby marked advertisement in accordance with 18 U.S.C. Section 1734 solely to indicate this fact.

Requests for reprints: Michiyuki Kanai, Department of Surgery, Tazuke-Kofukai Medical Research Institute and Kitano Hospital, 2-4-20, Ohgimachi, Kita-ku, Osaka 530-8480, Japan. Phone: 81-6-6312-1221; Fax: 81-6-6361-0588; E-mail: mkanai{at}kitano-hp.or.jp

Received 7/22/03; revised 12/19/03; accepted 2/19/04.


   REFERENCES
Top
 ABSTRACT
 INTRODUCTION
 PATIENTS AND METHODS
 RESULTS
 DISCUSSION
 REFERENCES
 

  1. Simon SM, Schindler M. Cell biological mechanisms of multidrug resistance in tumors. Proc Natl Acad Sci USA, 91: 3497-504, 1994.[Abstract/Free Full Text]
  2. Endicott JA, Ling V. The biochemistry of P-glycoprotein-mediated multidrug resistance. Annu Rev Biochem, 58: 137-71, 1989.[CrossRef][Medline]
  3. Wackers FJ, Berman DS, Maddahi J, et al Technetium-99m hexakis 2-methoxyisobutyl isonitrile: human biodistribution, dosimetry, safety and preliminary comparison to thallium-201 for myocardial perfusion imaging. J Nucl Med, 30: 301-11, 1989.[Abstract/Free Full Text]
  4. West DJ, Najm YC, Mistry R, et al The localization of myocardial ischemia with technetium-99m-methoxyisobutyl-isonitrile and single photon emission computed tomography. Br J Radiol, 62: 303-13, 1989.[Abstract/Free Full Text]
  5. O’Doherty MJ, Kettle AG, Welles P, Collins RE, Coakley AJ. Parathyroid imaging with technetium-99m-sestamibi: preoperative localization and tissue uptake studies. J Nucl Med, 33: 313-8, 1992.[Abstract/Free Full Text]
  6. O’Tuama LA, Treves ST, Larar JN, et al Thallium-201 versus technetium-99m-MIBI SPECT in evaluation of childhood brain tumors: a within-subject comparison. J Nucl Med, 34: 1045-51, 1993.[Abstract/Free Full Text]
  7. Hassan IM, Sahweil A, Constantinides C, et al Uptake and kinetics of Tc-99m hexakis 2 methoxy isobutyl-isonitrile in benign and malignant lesions in the lungs. Clin Nucl Med, 14: 333-40, 1989.[CrossRef][Medline]
  8. Kao CH, Wang SJ, Lin WY, et al Differentiation of single solid lesions in the lungs by means of single-photon emission tomography with technetium-99m methoxyisobutylisonitrile. Eur J Nucl Med, 20: 249-54, 1993.[Medline]
  9. Maublant J, de Latour M, Metas D, et al Technetium-99m-sestamibi uptake in breast tumor and associated lymph nodes. J Nucl Med, 37: 922-5, 1996.[Abstract/Free Full Text]
  10. Nakahara H, Noguchi S, Murakami N, et al Technetium-99m-sestamibi scintigraphy compared with thallium-201 in evaluation of thyroid tumors. J Nucl Med, 37: 901-4, 1996.[Abstract/Free Full Text]
  11. Chiu ML, Kronauge JF, Piwnica-Worms D. Effect of mitochondrial and plasma membrane potentials on accumulation of hexakis (2 methoxyisobutylisonitrile) technetium (I) in cultured mouse fibroblasts. J Nucl Med, 31: 1646-53, 1990.[Abstract/Free Full Text]
  12. Arbab AS, Koizumi K, Toyama K, Araki T. Uptake of technetium-99m-tetrofosmin, technetium-99m-MIBI and thallium-201 in tumor cell lines. J Nucl Med, 37: 1551-6, 1996.[Abstract/Free Full Text]
  13. Fujii H, Nakamura K, Kubo A, et al 99mTc-MIBI scintigraphy as an indicator of the chemosensitivity of anthracyclines in patients with breast cancer. Anticancer Res, 18: 4601-5, 1998.[Medline]
  14. Ceriani L, Giovanella L, Bandera M, et al Semi-quantitative assessment of 99Tcm-sestamibi uptake in lung cancer: relationship with clinical response to chemotherapy. Nucl Med Commun, 18: 1087-97, 1997.[Medline]
  15. Yamamoto Y, Nishiyama Y, Satoh K, et al Comparative study of technetium-99m-sestamibi and thallium-201 SPECT in predicting chemotherapeutic response in small cell lung cancer. J Nucl Med, 39: 1626-9, 1998.[Abstract/Free Full Text]
  16. Bom HS, Kim YC, Song HC, et al Technetium-99m-MIBI uptake in small cell lung cancer. J Nucl Med, 39: 91-4, 1998.[Abstract/Free Full Text]
  17. Kim YS, Cho SW, Lee KJ, et al Tc-99m-MIBI SPECT is useful for noninvasively predicting the response of MDR1 gene-encoded P-glycoprotein in patients with hepatocellular carcinoma. Clin Nucl Med, 24: 874-9, 1999.[CrossRef][Medline]
  18. Kao CH, Tsai SC, Wang JJ, et al Technetium-99m-sestamethoxyisobutylisonitrile scan as a predictor of chemotherapy response in malignant lymphomas compared with P-glycoprotein expression, multidrug resistance-related protein expression and other prognosis factor. Br J Haematol, 113: 369-74, 2001.[CrossRef][Medline]
  19. Taki J, Sumiya H, Asada N, et al Assessment of P-glycoprotein in patients with malignant bone and soft-tissue tumors using technetium-99m-MIBI scintigraphy. J Nucl Med, 39: 1179-84, 1998.[Abstract/Free Full Text]
  20. Bhatnagar A, Vezza PR, Bryan JA, et al Technetium-99m-sestamibi parathyroid scintigraphy: effect of p-glycoprotein, histology and tumor size on detectability. J Nucl Med, 39: 1617-20, 1998.[Abstract/Free Full Text]
  21. Leitha T, Glaser C, Lang S. Is early sestamibi imaging in head and neck cancer affected by MDR status, p53 expression, or cell proliferation?. Nucl Med Biol, 25: 539-41, 1998.[CrossRef][Medline]
  22. Gorlick R, Liao AC, Antonescu C, et al Lack of correlation of functional scintigraphy with 99mtechnetium-methoxyisobutylisonitrile with histological necrosis following induction chemotherapy or measures of p-glycoprotein expression in high-grade osteosarcoma. Clin Cancer Res, 7: 3065-70, 2001.[Abstract/Free Full Text]
  23. Japanese Gastric Cancer Association. Japanese Classification of Gastric Carcinoma, 2nd English Edition. Gastric Cancer, 1: 10-24, 1999.[CrossRef]
  24. Piwnica-Worms D, Chiu ML, Budding M, et al Functional imaging of multidrug-resistant P-glycoprotein with an organotechnetium complex. Cancer Res, 53: 977-84, 1993.[Abstract/Free Full Text]
  25. Hendrikse NH, Franssen EJ, van der Graaf WT, et al 99mTc-sestamibi is a substrate for P-glycoprotein and the multidrug resistance-associated protein. Br J Cancer, 77: 353-8, 1998.[Medline]
  26. Moretti JL, Cordobes MD, Starzec A, et al Involvement of glutathione in loss of technetium-99m-MIBI accumulation related to membrane MDR protein expression in tumor cells. J Nucl Med, 39: 1214-8, 1998.[Abstract/Free Full Text]
  27. Vergote J, Moretti JL, de Vries EG, Garnier-Suillerot A. Comparison of the kinetics of active efflux of 99mTc-MIBI in cells with P-glycoprotein-mediated and multidrug-resistance protein-associated multidrug-resistance phenotypes. Eur J Biochem, 15: 140-6, 1998.
  28. Zhou J, Higashi K, Ueda Y, et al Expression of multidrug resistance protein and messenger RNA correlate with 99mTc-MIBI imaging in patients with lung cancer. J Nucl Med, 42: 1476-83, 2001.[Abstract/Free Full Text]
  29. Chang CS, Huang WT, Yang SS, et al Effect of P-glycoprotein and multidrug resistance associated protein gene expression on Tc-99m MIBI imaging in hepatocellular carcinoma. Nucl Med Biol, 30: 111-7, 2003.[CrossRef][Medline]
  30. Waxman AD. Thallium-201 and technetium-99m methoxyisobutyl isonitrile (MIBI) in nuclear oncology Sandler MP Coleman RE Wackers FJTet al eds. . Diagnostic nuclear medicine, 3rd ed. p. 1261-74, Williams and Wilkins Baltimore, MD 1996.
  31. Walters JS, Norman A, Cunningham D, et al Long-term survival after epirubicin, cisplatin and fluorouracil for gastric cancer: results of a randomized trial. Br J Cancer, 80: 269-72, 1999.[CrossRef][Medline]
  32. Ross P, Nicolson M, Cunningham D, et al Prospective randomized trial comparing mitomycin, cisplatin, and protracted venous-infusion fluorouracil (PVI 5-FU) with epirubicin, cisplatin, and PVI 5-FU in advanced esophagogastric cancer. J Clin Oncol, 20: 1996-2004, 2002.[Abstract/Free Full Text]
  33. Bakker M, van der Graaf WT, Piers DA, et al 99mTc-sestamibi scanning with SDZ PSC 833 as a functional detection method for resistance modulation in patients with solid tumours. Anticancer Res, 19: 2349-53, 1999.[Medline]
  34. Chen CC, Meadows B, Regis J, et al Detection of in vivo P-glycoprotein inhibition by PSC 833 using Tc-99m sestamibi. Clin Cancer Res, 3: 545-52, 1997.[Abstract]



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