Using technetium-99m methoxyisobutylisonitrile lung single-photon-emission computed tomography to predict response to chemotherapy and compare with p-glycoprotein expression in patients with untreted small cell lung cancer

The purpose of this study was to predict chemotherapy response by technetium-99m methoxyisobutylisonitrile (Tc-99m MIBI) lung single-photon-emission computed tomography (SPECT) and compare P-glycoprotein (Pgp) expression in patients with untreated small cell lung cancer (SCLC). Before chemotherapy, 40 patients with untreated SCLC underwent Tc-99m MIBI lung SPECT. Immunohistochemical analyses were performed using multiple nonconsecutive sections of the biopsy specimens to detect Pgp expression. Chemotherapy response was evaluated in the third month after completion of treatment by clinical and radiological methods. Based on quantitative analyses, the tumor uptake ratios (TUR) of the 20 patients with good response (1.89 +/- 0.28) were significantly higher than that of the 20 patients with poor response (1.21 +/- 0.28) (p value < 0.05). Based on visual interpretation, all of the 20 patients (100%) with good response had positive Tc-99m TF lung SPECT findings and negative Pgp expression. Five of the other 20 patients (25%) with poor response had positive Tc-99m MIBI lung SPECT findings, and 12 of the other 20 patients (60%) with poor response had negative Pgp expression (p value < 0.05). Negative Tc-99m MIBI lung SPECT findings could predict poor response. Therefore, we concluded that Tc-99m MIBI lung SPECT can accurately predict the chemotherapy response, and Tc-99m MIBI lung SPECT findings can be partially compatible with Pgp expression in patients with untreated SCLC.     

Clinical role of Tc-99m-MIBI scintigraphy in non-Hodgkin's lymphoma.

This study was designed to investigate the relationship between Tc-99m-hexakis-2-methoxyisobutylisonitrile (MIBI) scintigraphy and outcome of treatment in patients with non-Hodgkin's lymphoma (NHL). Forty-five patients with NHL were studied with Tc-99m-MIBI before any treatment. Images of the lesions were obtained at 20 min and 2 h after radionuclide administration. Visual semi-quantitative interpretation was performed for Tc-99m-MIBI (grade 0-4) scintigraphy. Patients underwent 3-5 cycles of CHOP chemotherapy with/without involved field radiotherapy for large tumors. Their responses to treatment were evaluated at the end of chemotherapy and during the follow-up period. Forty of 45 patients (89%) showed abnormal uptake of Tc-99m-MIBI. There was no correlation between intensity of MIBI accumulation and response to chemotherapy. However, patients with negative or decreased MIBI activity 2 h after radionuclide administration showed worse response to chemotherapy compared to those with continued MIBI activity. MIBI activity could not predict the development of relapse in the follow-up study. In this study, the number of patients was small and we could not reach definite conclusions. However, we think that MIBI scintigraphy is not valuable for predicting the chemotherapy outcome in patients with NHL.     

Technetium-99m methoxyisobutylisonitrile chest imaging for small-cell lung cancer

Aims:This is a retrospective and adaptive randomizationstudy. The purpose of this study was to evaluate the relationshipbetween technetium-99m methoxyisobutylisonitrile (Tc-99m MIBI)chest-imaging results, chemotherapy response and P-glycoprotein (Pgp) ormultidrug resistance related protein (MRP) expression in small-cell lungcancer (SCLC). Patients and methods:Beforechemotherapy, 30 patients (11 females, 19 males, ages: 52–69years) with SCLC, including 14 extensive diseases without localizedproblems and 16 limited diseases in excess of solitary pulmonary nodule,underwent early chest imaging, including visual interpretation andquantitative analyses of tumor uptake ratio (TUR), 10 minutes afterintravenous injection of Tc-99m MIBI. Immunohistochemical analyses wereperformed, using multiple nonconsecutive sections of the biopsyspecimens, to detect Pgp and MRP expressions. Chemotherapy response wasevaluated in the third month after completion of treatment by clinicaland radiological methods. Results:All 15 (100%)of the SCLC patients with complete or partial response had positiveTc-99m MIBI chest SPECT results, but negative ones for both Pgp and MRPexpression. Twelve of the 15 (80%) SCLC patients with no responseor progressive disease had negative Tc-99m MIBI chest SPECT results andwere positive for either Pgp or MRP expression(P < 0.05). Negative Tc-99m MIBI chest SPECTresults predicted complete or partial response. The TUR of patients withcomplete or partial response (1.91 ± 0.29 with a 95%confidence interval (95% CI): 1.75–2.07) was significantlyhigher than that of patients with no response or progressive disease(1.19 ± 0.28 with a 95% CI: 1.04–1.35). Conclusion:Tc-99m MIBI chest images are a potential toolfor understanding Pgp and MRP expressions in SCLC and for predictingpatient chemotherapy response.     

Arterial blood pressure, serum calcium and PTH in elderly men with parathyroid tumors and primary hyperparathyroidism

In patients with parathyroid tumors and primary hyperparathyroidism (PHPT), the relationship between arterial blood pressure (BP) and both serum calcium and parathyroid hormone (PTH) is still unclear. The aim of this study was to investigate whether a correlation exists between BP and the main biochemical parameters in men with confirmed sporadic PHPT due to a solitary parathyroid adenoma. A series of 38 elderly (>64 years) men (median age 69 years, range 65-78 years) were enrolled in the study. Twenty-nine (76.3%) were asymptomatic, while 9 (23.7%) had renal diseases (i.e. renal stones, impaired renal function). The main preoperative biochemical parameters were the following: serum calcium=2.77±0.25 mmol/l, PTH=166.5±157.0 ng/l, alkaline phosphatase (ALP)=107.6±37.0 U/l, and creatinine=82.5±8.1 μmol/l. In each patient, the BP was recorded three times at 2-3 min intervals using an automatic device, and the mean values were recorded. All patients successfully underwent parathyroidectomy. As expected, there was a significant relationship between age and both systolic and diastolic BP (β=0.39, p=0.018; β=0.41, p=0.014, respectively). There was also a correlation between systolic and diastolic BP (β=0.39, p=0.01) and between serum calcium and PTH (β=0.51, p=0.008). A weak relationship (β=0.28, p=0.04) between serum calcium and creatinine was also found. However, no significant relationship between systolic or diastolic BP and serum calcium (β=0.012, p=0.94; β=0.065, p=0.71) or PTH (β=0.08, p=0.65; β=0.17, p=0.32), respectively, was observed. In conclusion, our study confirms that in men with parathyroid tumors and PHPT, the BP values are independent of both serum calcium and PTH levels.     

99mTc-MIBI肺肿瘤显像与MRP表达的关系

目的:探讨原发性肺癌99mTc-MIBI显像与多药耐药相关蛋白(MRP)表达的关系。方法:对22例原发性肺癌行99mTc-MIBI早期(30min)、延迟(180min)显像,应用免疫组化方法检测手术标本中MRP表达水平,比较早期摄取比值(EUR)、晚期摄取比值(DUR)及储留指数(RI)与MRP表达的关系。结果:99mTc-MIBI早期、延迟显像阳性率分别为90.9%、81.8%,MRP表达阳性率27.3%;MRP表达阳性组与阴性组间与99mTc-MIBI的EUR、DUR及RI未见显著性差异。结论:原发性肺癌组织对99mTc-MIBI聚集、洗脱与MRP表达关系不大,应用99mTc-MIBI显像检测原发性肺癌MRP基因的表达临床价值不大。     

Quickly predicting chemotherapy response to paclitaxel-based therapy in non-small cell lung cancer by early technetium-99m methoxyisobutylisonitrile chest single-photon-emission computed tomography.

The purpose of this study was to retrospectively predict the chemotherapy response to paclitaxel in non-small cell lung cancer (NSCLC) using technetium-99m methoxyisobutylisonitrile (Tc-99m MIBI) chest single-photon-emission computed tomography (SPECT) to detect the expression of multidrug-resistance-mediated Mr 170,000 P-glycoprotein. Before chemotherapy with Paclitaxel (Taxol), 30 patients with stage IIIb or IV NSCLC were enrolled in this study. Early chest SPECT 10 min after i.v. injection of Tc-99m MIBI was performed to qualitatively interpret Tc-99m MIBI chest SPECT visually and quantitatively calculate early tumor:normal lung ratios (T:NL) for quick assessment of multidrug-resistant P-glycoprotein expression in NSCLC. On the basis of qualitatively visual interpretation of early Tc-99m MIBI chest SPECT, all of 15 (100%) cases with good response to chemotherapy with Taxol could be detected but 10 (67%) of 15 cases with poor response could not be detected. Early Tc-99m MIBI chest SPECT could correctly predict chemotherapy response in 25 (83%) of 30 of cases. The early T:NL were 3.30 +/- 0.82 for 15 patients with good response and 2.02 +/- 0.19 for 5 patients with poor response. The differences were significant (P < 0.05) by independent Student t tests. However, no significant differences were found for other prognostic factors (age, sex, tumor size, tumor location, stage, and cell type) between good-response and poor-response patients. Early Tc-99m MIBI chest SPECT has the potential to predict chemotherapy response to Paclitaxel.     

乳腺肿瘤摄取99Tcm-甲氧基异丁基异睛与耐多药蛋白表达的关系

目的研究乳腺肿瘤摄取99Tcm-甲氧基异丁基异睛 (99Tcm-MIBI)与耐多药蛋白表达水平间的相关性.方法 30例经病理证实的原发性浸润性导管癌患者,均行99Tcm-MIBI早期显像和延迟显像.对显像阳性的肿块计算感兴趣区与对侧正常相应部位的放射性计数比值,以早期摄取比值(EUR)和延迟摄取比值(DUR)计算滞留指数(RI).以免疫组织化学法检测手术切除标本肿瘤组织的P-糖蛋白(P-gp)和多药耐药相关蛋白(MRP)的表达水平.数据分别进行配对t检验、Pearson相关分析及偏相关分析.结果 P-gp的平均表达水平为0.1183±0.0700,MRP的平均表达水平为0.1195±0.0522.P-gp和MRP的表达水平在RI≥0和RI＜0的组中,差异有显著性.P-gp的表达与RI(r=-0.919,P=0.001)、DUR(r=-0.675,P=0.001)和MRP(r=0.549,P=0.002)有相关性,与EUR(r=-0.097,P=0.610)无相关性.MRP的表达与RI(r=-0.547,P=0.002)有相关性,与EUR(r=0.292,P=0.117)、DUR(r=-0.173,P=0.361)无相关性.P-gp与MRP的表达有相关性(r=0.549,P=0.001).偏相关分析则显示,P-gp的表达与RI(r=-0.8847,P=0.001)有显著相关性,MRP的表达与RI(r=-0.1296,P=0.512)无相关性.结论 99Tcm-MIBI乳腺显像与P-gp的表达呈负相关关系,与MRP未见有相关性.     

An incidentally detected breast cancer on tc-99m MIBI cardiac scintigraphy

Tc-99m methoxyisobutylisonitrile (MIBI) scintigraphy is generally used as a second-line diagnostic tool for obscured breast lesions. When the entire field of view is examined carefully, it is often possible to detect additional lesions unrelated to the initial intent and purpose of the examination. Herein we present a case of breast cancer incidentally detected by cardiac Tc-99m MIBI scintigraphy. An area of uptake was detected in the breast during a cardiac imaging test. Further evaluation of this lesion revealed a histopathological diagnosis of invasive ductal carcinoma of the breast. Sensitivity of this scintigraphic technique is not enough sufficient to use this test as a screening test for breast cancer, but it may provide supplemental information. Since it is not uncommon to find incidental lesions during imaging studies, examination of the image field may help clinicians find otherwise unrecognized or undiagnosed pathologies.     

The multidrug resistance of in vitro tumor cell lines derived from human breast carcinoma MCF-7 does not influence pentavalent technetium-99m-dimercaptosuccinic Acid uptake

The main causes of multidrug resistance (MDR) are overexpression of P-glycoprotein (P-gp) and multidrug resistance-associated protein isoform 1 (MRP1) often associated with high levels of glutathione (GSH). We investigated whether MDR phenotype can influence Tc-99m-(V)-DMSA [pentavalent technetium-99m-dimercaptosuccinic acid] entry by comparing its uptake with that of Tc-99m-sestamibi (MIBI) on an in vitro model of sensitive (MCF-7) and variant resistant cell lines. Drug resistance was assessed by immunoblotting, GSH measurement, and 3-[4,5-dimethylthiazol-2-yl]-2,5,diphenyl tetrazolium bromide (MTT) assay. To correlate MDR phenotype with tracer accumulation, uptakes were performed with and without P-gp and MRP1 inhibitors and after GSH modulation. Similar accumulation of Tc-99m-(V)-DMSA was observed in all cell lines and the use of MDR reversals did not enhance its uptake. Our results demonstrate clearly that Tc-99m-(V)-DMSA uptake is not related to either P-gp and MRP1 expression, or GSH levels. In contrast, Tc-99m-MIBI accumulation is inversely proportional to the cell MDR phenotype. The combination of Tc-99m-(V)-DMSA and Tc-99m-MIBI may be a useful tool for noninvasive detection of malignant sites and their chemoresistance status.     

Sensitivity of Gastric Cancer Cells to Chemotherapy Drugs in Elderly Patients and Its Correlation with Cyclooxygenase-2 Expression

Objective: To explore the sensitivity of gastric cancer cells to chemotherapy drugs in elderly patients andits correlation with cyclooxygenase-2 (COX-2) expression in cancer tissue. Materials and Methods: Forty-threeelderly patients with gastric cancer (observation group) and 31 young patients with gastrointestinal tumors(control group) who were all diagnosed by pathology and underwent surgery in the 89th Hospital of ChinesePeople’s Liberation Army were selected. Drug sensitivity testing of tumor cells in primary culture was carriedout in both groups using a methyl thiazolyl tetrazolium (MTT) method, and the expression of COX-2 and thefactors related to multi-drug resistance (MDR) in cancer tissue were assessed by immunohistochemistry. Results:The inhibition rates (IR) of vincristine (VCR), 5-fluorouracil (5-FU), oxaliplatin (L-OHP), mitomycin (MMC)and epirubicin (eADM) on tumor cells in the observation group were dramatically lower than in the controlgroup, with statistical significance (P<0.05 or P<0.01). The positive rates of COX-2, glutathione s-transferase-π(GST-π) and P glycoprotein (P-gp) expression in cancer tissue in the observation group were all higher than incontrol group (P<0.05), while that of DNA topoisomerase IIα (TopoIIα) expression lower than in the control group(P<0.01). In the observation group, COX-2 expression in cancer tissue had a significantly-positive correlationwith GST-π and P-gp (r=0.855, P=0.000; r=0.240, P=0.026), but a negative correlation with TopoIIα (r=−0.328,P=0.002). In the control group, COX-2 expression in cancer tissue was only correlated with P-gp positively(r=0.320, P=0.011). Bivariate correlation analysis displayed that COX-2 expression in cancer tissue in theobservation group had a significantly-negative correlation with the IRs of 5-FU, L-OHP, paclitaxel (PTX) andeADM in tumor cells (r=−0.723, P=0.000; r=−0.570, P=0.000; r=−0.919, P=0.000; r=−0.781, P=0.000), but withhydroxycamptothecine (HCPT), VCR and 5-FU in the control group (r=−0.915, P=0.000; r=−0.890, P=0.000;r=−0.949, P=0.000). Conclusions: Gastric cancer cells in elderly patients feature stronger MDR, which may berelated to high COX-2 expression.     

Expression of p53, Ki-67 and Bcl-2 in parathyroid adenoma and residual normal tissue

The aim of this study was to investigate the expression of Ki-67, bcl-2 and p53 in parathyroid adenomas and their residual rim of normal parathyroid tissue. Specimens from 26 parathyroid adenomas were studied by immunohistochemical analysis for Ki-67, bcl-2 and p53 expression. Positive findings were noted for p53 in 4 (15%) adenomas and none of the residual rims of normal parathyroid tissue (p = 0.055); for Ki-67 in 15 (56%) adenomas and none of the residual rims of normal parathyroid tissue (p = 0.00002); and for bcl-2 in 19 (73%) adenomas and 8 (31%) residual rims of normal parathyroid tissue (p < 0.01). The high rate of Ki-67 expression may indicate susceptibility of parathyroid adenomas to clonal proliferation. The weak immunoreactive expression of p53, combined with a relatively strong expression of bcl-2, may contribute to the characteristic slow progression of these tumors.     

Expression of mediated P-glycoprotein multidrug resistance related to Tc-99m MIBI scintimammography results

We prospectively studied a total of 24 patients with breast cancer to evaluate the relationship between the degree of accumulation of technetium-99m sestamibi (Tc-99m MIBI) and p-glycoprotein (Pgp) expression in tumor tissues. All 24 patients underwent Tc-99m MIBI scintimammography before surgery or biopsy. Immunohistochemical studies were performed on multiple non-consecutive sections of the same tumor using a Pgp specific monoclonal antibody, JSB-1. Planar images were started 10 min after injection of Tc-99m MIBI. Tumor to background (T/B) ratios calculated from the planar images were correlated with Pgp expression as determined by immunohistochemical studies. The T/B ratios were significantly lower for tumors in eight patients with positive Pgp expression (Group 1) than in 16 patients with negative expression (Group 2) (1.40+/-0.11 and 2.76+/-0.60, P<0. 05). Our data confirmed that Tc-99m MIBI scintimammography is useful for determination of the presence of multidrug resistance due to Pgp expression in patients with breast cancer.     

宫颈腺癌组织ERK1/2和p16^（INK4a）及P-gp表达与耐药相关性分析

目的：探讨细胞外信号调节激酶1/2（ERK1/2）、p16INK4a及P-糖蛋白（P-gp）与宫颈腺癌耐药的关系。方法：PV9000免疫组化二步法检测化疗敏感组（14例）及耐药组（25例）宫颈腺癌活检组织中ERK1/2、p16INK4a及P-gp蛋白的表达情况,分析ERK1/2、p16INK4a及P-gp在两组的表达差异、3者的表达相关性及与宫颈腺癌患者3年生存率的关系。结果：ERK1/2在耐药组及敏感组的高表达率分别为72.0%（18/25）及35.7%（5/14）,差异有统计学意义,U=96,P=0.016;P-gp在耐药组的高表达率为76.0%（19/25）,显著高于敏感组的28.6%（4/14）,差异有统计学意义,U=102,P=0.026;p16INK4a蛋白在耐药组及敏感组的表达差异无统计学意义,U=129,P=0.140。ERK1/2与p16INK4a的表达呈正相关,r=0.571,P〈0.001;ERK1/2与P-gp的表达呈正相关,r=0.364,P=0.023;p16INK4a与P-gp的表达无明显相关性,r=0.254,P=0.132。ERK1/2高表达与低表达患者的3年生存率分别为60.9%（14/23）和93.8%（15/16）,差异有统计学意义,χ2=4.723,P=0.030;而p16INK4a高表达与低表达患者的3年生存率分别为68.0%（17/25）和85.7%（12/14）,差异无统计学意义,χ2=1.355,P=0.244;P-gp高表达与低表达患者的3年生存率分别为65.2%（15/23）和87.5%（14/16）,差异无统计学意义,χ2=2.347,P=0.125。结论：ERK1/2和P-gp的高表达与宫颈腺癌耐药相关;ERK1/2的表达情况不仅可为宫颈腺癌化疗用药提供参考,而且可作为宫颈腺癌判断预后的指标。     

肺癌组织P-糖蛋白表达与原位细胞凋亡、增殖、凋亡相关基因关系及其临床意义

目的探讨肺癌组织P-糖蛋白(P-glycoprotein,P-gp)表达与细胞凋亡、增殖及凋亡相关基因的关系及其预后意义.方法应用末端脱氧核糖核酸转移酶法(TUNEL)检测凋亡细胞,免疫组织化学检测耐药及凋亡相关基因蛋白表达.结果非小细胞肺癌(NSCLC)P-糖蛋白阳性率22.2%,小细胞肺癌(SCLC)阳性率11.5%.凋亡指数(Apoptosisindex,AI)和增殖指数(PCNA-labelingindex,PCNA-LI)呈高度负相关(r=-0.7358,P<0.01).P-gp阳性者,AI和PCNA-LI高于P-gp阴性者,PCNA-LI差异有显著性(P<0.01).P-gp与bcl-2表达相关(r=0.5637,P<0.05),与P21WAF1/CIPI无关(r=0.2405,P>0.05).多因素Cox回归分析显示,P-gp及AI有预后意义.结论P-gp与细胞凋亡、增殖、凋亡相关基因相关,且具预后意义.     

胃癌中P-糖蛋白、多药耐药相关蛋白、肺耐药蛋白的表达及其意义

 目的　检测胃癌组织中P-糖蛋白（P-gp）、多药耐药相关蛋白（MRP）、肺耐药蛋白（LRP）的表达,分析其与胃癌临床病理因素的关系。方法　采用免疫组织化学SP法对59例胃癌患者癌组织进行研究。结果　在59例胃癌患者中P-gp阳性率最高[86.4 %（51例）],其次为LRP[84.7 %（50例）],二者呈正相关（r＝0.803）;MRP阳性率最低[27.1 %（16例）]。P-gp、MRP、LRP与分化程度无关（均P＞0.05）。P-gp与临床分期呈正相关（r＝0.742）,MRP、LRP均与胃癌浸润深度、淋巴结转移与否及分化程度无关。结论　P-gp、MRP、LRP在未接受化疗胃癌组织中高表达,提示胃癌中存在P-gp、MRP、LRP介导的原发性耐药。     

The immunoscintigraphic use of Tc-99m-labelled monoclonal anti-CEA antibodies (BW 431/26) in patients with suspected primary, recurrent and metastatic breast cancer

The discrepancy between serum CEA levels and CEA tissue expression in patients with breast cancer is well known. Whereas immunohistochemistry shows positive CEA expression in 70-90%, the serum CEA levels are often within the normal range. We performed immunoscintigraphy and SPECT with a Tc-99m labelled anti-CEA monoclonal antibody (MAb BW 431/26) in 46 women with suspected breast cancer or recurrence. The results of anti-CEA immunoscintigraphy, mammography, serum CEA levels and immunohistochemistry were evaluated according to the histology of the tumor. Histology verified breast cancer or recurrence (pT1 [n = 7], pT2 [n = 17], pT3 [n = 3], pT4 [n = 3]) in 30 out of 46 patients; benign breast disease such as fibrocystic disease, fibroadenoma, fatty necrosis or chronic mastitis was responsible for suspicious mammographic findings in 16 patients. Immuno-SPECT showed 25 true-positive, 5 false-negative, 11 true-negative and 5 false-positive findings (sensitivity 83%, specificity 69%). Anti-CEA immuno-SPECT of 2 patients with bone metastasis showed all lesions previously detected by bone scintigraphy to be CEA-expressing metastases. In contrast, serum CEA levels were slightly elevated in only 5 out of 30 patients with histologically verified breast cancer (sensitivity 17%). The results of immuno-histochemistry were surprising; tissue CEA expression could be demonstrated in only 5 patients with breast cancer. According to our experiences with this Tc-99m labelled anti-CEA MAb, immuno-SPECT is a suitable additional method for the diagnosis of breast cancer and especially of recurrence. Pre-operative serum CEA levels give no support for the differentiation between benign and malignant breast tumors.     

Scintimammographic findings of phyllodes tumor of the breast in a double-phase study with Tc-99m (V)DMSA and Tc-99m MIBI: a case report

We present a case of phyllodes tumor of the breast in a 78-year-old woman evaluated with Tc-99m (V)DMSA and Tc-99m MIBI scintimammography, acquired in separate sessions (10 and 60 min post-injection). Tc-99m (V)DMSA was accumulated intensely within the mass [tumor to background ratio (T/B) >3], whereas Tc-99m MIBI had significantly lower uptake (T/B 1.9). Histology revealed a phyllodes tumor (maximum diameter 15 cm) and approximately three mitoses over 10 fields of view (FOV) x40, foci of epithelial hyperplasia and apocrine metaplasia. Stromal Ki-67 expression was 7%. The tumor was considered to be benign and the patient underwent mastectomy. One year later the patient presented with local malignant recurrence of the disease with over 15 mitoses per 10 FOV. Tc-99m (V)DMSA seems to have an advantage over Tc-99m MIBI in detecting mesenchymal tumors with unforeseen biological behavior and Ki-67 over-expression, such as phyllodes tumors, even with primary negative histological findings.     

Prediction of chemotherapeutic response by Technetium 99m--MIBI scintigraphy in breast carcinoma patients

BACKGROUND: Significance of Technetium 99m ((99m)Tc)-MIBI scintigraphy in the prediction of response to anthracylines and taxanes (both are substrates for P-glycoprotein [P-gp]) as well as relation between (99m)Tc-MIBI uptake and P-gp or MDR1 mRNA expression in tumors were studied in patients with breast carcinoma. METHODS: Forty-six female patients with locally advanced (n = 15) or metastatic (n = 31) breast carcinoma were recruited in this study. Before chemotherapy (epirubicin and cyclophosphamide [n = 20] or decetaxel [n = 26]), (99m)Tc-MIBI scintigraphy was performed to obtain the T/N (tumor to normal tissue) ratios of (99m)Tc-MIBI uptake at 10 minutes (T/N[e]) and at 180 minutes (T/N[d]) after the (99m)Tc-MIBI injection. Expression of MDR1 mRNA and P-gp in tumors (n = 32) were determined by a quantitative real-time polymerase chain reaction and immunohistochemistry, respectively. RESULTS: Clinical significance of T/N(e) and T/N(d) ratios in the prediction of chemotherapeutic response was evaluated using the arbitrary cutoff values of 3.0 for T/N(e) ratios and 2.0 for T/N(d) ratios. Positive predictive value, negative predictive value, and diagnostic accuracy of T/N(d) ratios (81.0%, 96.0%, and 89.1%, respectively) were higher, although statistically not significant, than those of T/N(e) ratios (73.3%, 77.4%, and 76.1%, respectively), and these values were not affected by type of chemotherapy. MDR1 mRNA levels were not significantly different between the lesions with high (> or = 2.0) and low (< 2.0) T/N(d) ratios, but P-gp expression was significantly (P < 0.01) higher in the lesions with low T/N(d) ratios than in those with high T/N(d) ratios. CONCLUSIONS: T/N(d) ratios determined by (99m)Tc-MIBI scintigraphy are useful in the prediction of response to chemotherapy with epirubicin and cyclophosphamide or docetaxel as well as in the in vivo evaluation of P-gp expression status in tumors in patients with locally advanced or recurrent breast carcinoma.