Evaluation of reversal effect of 2-DG on multidrug resistance by detecting uptake of 99mTc-MIBI in HNE-1/DDP cells / 中国药理学通报

Aim To evaluate the reversal effect of 2-deoxy-D-glucose ( 2-DG ) on multidrug resistance ( MDR) by observing the uptake change of 99m Tc-MIBI in HNE-1/DDP cells, and to explore its mechanism. Methods The uptake of 99m Tc-MIBI in HNE-1/DDP cells under different concentrations of 2-DG was detec-ted by γ-counter, and the clearance rates of 99m Tc-MI-BI in HNE-1 cells and HNE-1/DDP cells after treated with 2-DG (10 mmol·L-1 ) were compared. The con-tent of ATP in HNE-1/DDP cells was detected after treated with 2-DG. P-glycoprotein ( P-gp ) and multi-drug resistance-associated proteins ( MRP ) expression were measured by Western blot. Apoptotic HNE-1/DDP cells treated with DDP alone or combined with 2-DG (10 mmol·L-1 ) were detected by propidium io-dide ( PI ) staining. Results The clearance rate of 99m Tc-MIBI in HNE-1/DDP cells was 54. 8%, which was significantly higher than that ( - 41. 3%) in HNE-1 cells (P<0. 01). The clearance rate of 99mTc-MIBI in HNE-1/DDP cells was -203. 7% after treat-ment with 2-DG ( 10 mmol · L-1 ) , which could be significantly reduced compared with the control group ( P<0. 01 ) . The level of ATP was 55 . 69% compared with the negative control group and the expression of P-gp and MRP protein decreased dramatically in HNE-1/DDP. With the combination of 2-DG and DDP, the ap-optotic rate of HNE-1/DDP cells reached 49 . 4%which was significantly higher than DDP treated group (22. 5%) . Conclusion Multidrug resistance and the reversal effect of 2-DG on multidrug resistance could be evaluated effectively by detecting the uptake change of 99m Tc-MIBI in HNE-1/DDP cells. The mechanism may be related with the inhibition of ATP level and the re-duced expression of P-gp and MRP protein in cancer cells.

The Value of (99m) Tc-MIBI-Heart SPECT in Myocardial Contusion

PURPOSE: This study analyzed the value of (99m)Tc - M I B I SPECT(Single Photon Emission Com-puted Tomography) in the diagnosis of myocardial contusion after blunt chest trauma . METHODS: We evaluated 24 patients with cardiac contusions after blunt chest trauma who were diagnosed by clinical symptoms, chest x-ray, electrocardiogram(ECG), and Creatine phospho-kinase(CPK). (99m)Tc-MIBI SPECT was performed within 48 hours along with the above tests prospectively. RESULTS: 1. Among the 24 patients, 14 patients were finally diagnosed as having a myocardial contusion by means of ECG, echocardiography, (99m)Tc-MIBI SPECT, and cardiac enzyme. 2. The sensitivity, specificity and accuracy of (99m)Tc - MIBI SPECT were 46.7%, 66.7%, and 54.2%, respectively. The same results for initial ECG were 46.6%, 88.9%, and 62.5%. 3. For those who had positive findings in (99m)Tc - MIBI SPECT, average hospital stay was 14.5 days and abnormal electrocardiogram was found in 90.0%. However, for those who had negative findings, average hospital stay was 11.2 days and abnormal electrocardiogram was found in 35.7%. CONCLUSION: (99m)Tc-MIBI SPECT is not a definite modality in diagnosing myocardial contusion, but can be useful in diagnosing and determining the need for hospitalization after cardiac contusion.

The Value of (99m) Tc-MIBI-Heart SPECT in Myocardial Contusion

PURPOSE: This study analyzed the value of (99m)Tc - M I B I SPECT(Single Photon Emission Com-puted Tomography) in the diagnosis of myocardial contusion after blunt chest trauma . METHODS: We evaluated 24 patients with cardiac contusions after blunt chest trauma who were diagnosed by clinical symptoms, chest x-ray, electrocardiogram(ECG), and Creatine phospho-kinase(CPK). (99m)Tc-MIBI SPECT was performed within 48 hours along with the above tests prospectively. RESULTS: 1. Among the 24 patients, 14 patients were finally diagnosed as having a myocardial contusion by means of ECG, echocardiography, (99m)Tc-MIBI SPECT, and cardiac enzyme. 2. The sensitivity, specificity and accuracy of (99m)Tc - MIBI SPECT were 46.7%, 66.7%, and 54.2%, respectively. The same results for initial ECG were 46.6%, 88.9%, and 62.5%. 3. For those who had positive findings in (99m)Tc - MIBI SPECT, average hospital stay was 14.5 days and abnormal electrocardiogram was found in 90.0%. However, for those who had negative findings, average hospital stay was 11.2 days and abnormal electrocardiogram was found in 35.7%. CONCLUSION: (99m)Tc-MIBI SPECT is not a definite modality in diagnosing myocardial contusion, but can be useful in diagnosing and determining the need for hospitalization after cardiac contusion.

Prediction of Histologic Grade and Multidrug Resistance of Brain Tumors Using Brain SPECT

OBJECTIVE: Computerized tomography(CT) and magnetic resonance imaging(MRI) are very useful in detection of structural change in the brain including tumors. However, they can not inform functional and biological behavior of such lesions. 99m Tc-Methoxyisobutyl isonitrile(MIBI) is considered as a substrate for MDR1 gene-encoded permeability glycoprotein(P-gp) and it has been used in the evaluation of multidrug resistance(MDR) in various tumors. The purpose of the study is to demonstrate the presence of MDR in brain tumor and brain tumor grading by an external imaging with 201Thallium and 99m Tc-MIBI SPECT. METHODS: 201Thallium and 99m Tc-MIBI SPECT were performed in 18 patients with malignant tumors and in six patients with benign tumors. Immunohistochemical staining(IHC) of the tumor specimen for P-gp was also performed. The histologic grading of the tumors and immunohistochemical staining for P-gp were compared to the dual brain SPECT findings of 201Thallium and 99m Tc-MIBI SPECT studies. Brain tumor with positive 201Thallium SPECT and negative 99m Tc-MIBI SPECT is considered to be multidrug resistance. An uptake index obtained from brain SPECT was used for tumor grading. MDR1 gene-encoded P-gp was assessed by immunohistochemical staining using a monoclonal antibody for P-gp. RESULTS: The malignant group showed significantly higher uptake indices in the 201Thallium and 99m Tc-MIBI SPECT than benign group. The uptake index of 99m Tc-MIBI SPECT was inversely correlated with P-gp immunohistochemical staining without statistical significance. CONCLUSION: 201Thallium and 99m Tc-MIBI SPECT are useful for predicting histologic grade of brain tumors, and 99m Tc-MIBI SPECT might be useful for predicting the presence of MDR protein.

Clinical detection and modulation strategy of lung cancer multidrug resistance with membrane transport proteins as the target / 解放军医学杂志

The major problem in lung cancer chemotherapy is the emergence of inherent and acquired drug resistance of the cancer cells. The cancer becomes resistant not only to the drugs used initially, but also to those to which it has not yet been exposed, This condition is known as multidrug resistance (MDR). MDR has been found to be related to three members of the ABC-superfamily of membrane transport proteins (transporters) and one member of the non-ABC-superfamily of transporter. The formers are P-glycoprotein (P-gp), multidrug resistance-associated protein (MRP), and breast cancer resistance pro-tein (BCRP). The latter is lung resistance-related protein (LRP). These findings provided new molecular targets to predict drug resistance, and an atraumatic detection method by using Tc-99m methoxyisobutyl isonitrile ( 99m Tc-MIBI ) SPECT has been developed for predicting MDR in lung cancer. Based on these transporters, different strategies are tried attempting to reverse drug resistance in lung cancer. Encouraging results have been acquired, but further research is necessary.

The comparative study of nuclein hypoxia imaging,tumoraffin imaging and CT in the diagnosis of lung neoplasms / 中国医师杂志

Objective To investigate the value of ~(99m)Tc-HL91 hypoxia imaging,~(99m)Tc-MIBI tumoraffin and computered tomography(CT) in the diagnosis of lung cancer.Methods The ~(99m)Tc-HL91 hypoxia imaging,~(99m)Tc-MIBI tumoraffin and CT were performed in 50 patients with lung neoplasm confirmed by pathology.Results There was not significant difference in the sensitivity of three imaging examination methods.The specificity of ~(99m)Tc-HL91 hypoxia imaging was obviously higher than that of ~(99m)Tc-MIBI tumoraffin and CT.The accuracy of ~(99m)Tc-HL91 hypoxia imaging was higher than that of ~(99m)Tc-MIBI tumoraffin,and had not significance difference with that of CT.The sensitivity,specificity and accuracy of the combination of three imaging examination methods in the diagnosis of lung cancer were 96.9%,100% and 98%,respectively.Conclusion The ~(99m)Tc-HL91 hypoxia imaging is valuable in diagnosing lung cancer and the diagnostic accuracy may be further improved with the combination of ~(99m)Tc-MIBI tumoraffin and CT.

Detection of primary breast cancer and axillary lymph node metastasis by ~(99m)Tc-MIBI prone scintimamorgaphy / 中国普通外科杂志

Objective To prospectively study the sensitivity and specificity of 99m Tc Methoxyisobutyl Isonitrile( 99m Tc MIBI) scintimammorgaphy in the detection of both primary breast cancer and axillary lymph node metastasis. Methods Eighty four consecutive women suspicious of breast cancer under clinical examination were checked by the scintimammorgaphy of planar prone imaging in three planar views(5～8?min/view). The entire breast and ipsilateral axillary region were included in the field of view. Biopsy of resectional breast and lymph node were performed within 10 days after scintimammography. Results There were 51 primary breast cancer(7 different histologic types) and 33 benign breast lesion(4 histologic types) in this series. The sensitivity of scintimammography for detecting primary breast cancer was 90.20%(46/51) and the specificity was 93.93%(31/33). Metastatic axillary lymph nodes were seen in 25 of the 51 patients. The sensitivity of scintimammography to detect metastatic lymph node was 84.0%(21/25) and the specificlty was 88.46%(23/26). Conclusions The results of this study indicate that the scintimammography has high diagnosis rate in detecting breast cancer and axillary lymph node metastasis.

Technetium-99m-MIBI SPECT in Intracranial Lesions

Thallium(T1) has recently been used as a pharmaceutical for tumor imaging and staging. The aim of this study was to evaluate the clinical significance of the T1 analogue, 99m-Tc-MIBI(methoxyisobutylisonitrile), for imaging of intracranial lesions. The advantages of MIBI were though to be a lower radiation exposure and better image quality than with T1. 99m-Tc-MIBI SPECT studies were done in 30 patients with brain tumors(14 astrocytomas, 7 meningiomas, 2 hemangioblastomas, 2 craniopharyngiomas, 1 ependymoma, 4 metastatic tumors) and in twelve patients with non-tumorous lesions(2 abscesses, 2 granulomas, 2 cysticercosis, 3 old intracerebral hemorrages, 1 infarction. 1 postoperative gliosis, 1 unknown pathology), and semiquantitative assessment of tracer uptake was made using a ratio of radioactivity for lesion to contralateral normal brain(Lesion/Contralateral normal brains ; L/C). Twenty six of thirty tumors showed high L/C ratios(>1.5) and another four tumors low L/C ratios(<1.5). Of 12 non-tumorous intracranial lesions, 11 showed little or no uptake, but one moderate uptake. In conclusion, it appears that brain tumors show more intense focal uptake than non-tumorous brain lesions. However, further studies would be warranted to evaluate the clinical significance of MIBI SPECT in tumor staging(grading) and in differentiating necrosis from tumor regrowth more clearly.

Chest Pain during Dipyridamole (99m)Tc-MIBI Myocardial Scan

BACKGROUND: Dipyridamole-stressed myocardial scan is a useful diagnostic tool of coronary artery disease, however clinical significance of dipyridamole-induced chest pain is not well documented. METHOD: To investigate clinical significance of chest pain after intravenous dipyridamole infusion, reversibility score was calculated in 320 patients using reconstructed polar map of dipyridamole (99m)Tc-MIBI myocardial perfusion scan. In 81 patients who undertook both coronary angiogram and (99m)Tc-MIBI myocardial scan within 5 weeks, jeopardy score and myocardial ischemic score were calculated using coronary angiogram. RESULT: Group 1 consisted of the patients with typical chest pain, group 2 consisted of the patients with atypical chest pain, and group 3 consisted of the patients without chest pain. Mean reversibility score of group 1(90.0+58.4) was significantly higher(p<0.05) than that of group 3(64.7+/-44.5). Mean myocardial ischemic score of group 1(632.5+/-272.3) was significantly(p<0.05) higher than that of group 2(356.9+/-244.6) or group 3(287.5+/-257.7). Proportion of normal coronary angiogram in group 1(2/27, 7.4%) was significantly lower than that in group 3(11/34, 32.4%). CONCLUSION: These findings suggest that typical chest pain after intravenous dipyridamole infusion might represent myocardial ischemia and suggest more severe coronary artery disease.

A Case of Giant Coronary Arteriovenous Fistula with Coronary Steal Demonstrated by Dobutamine Stress Echocardiography and (99m)Tc-MIBI SPECT

We present a case of giant coronary arteriovenous fistula between left main coronary artery and pulmonary artery in a 60-year-old female who presented with anginal symptom. Dobutamine stress echocardiography and myocardial perfusion scan with (99m)Tc-MIBI revealed a reversible perfusion defect in the septal region. Coronary angiography demonstrated a giant coronary arteriovenous fistula origination from the left main coronary artery and draining into the pulmonary artery. This appears to be the first case in which dobutamine stress echocardiography and myocardial perfusion scan with (99m)Tc-MIBI demonstrated myocardial ischemia due to coronary steal in patient with a coronary arteriovenous fistula.

(99m)Tc-MIBI SPECT Findings in Diabetics with Coronary Artery Disease

BACKGROUND: Evaluation of coronary artery disease(CAD) by radionuclide myocardial perfusion scintigraphy is safe, convenient and informative for diagnosis of CAD & assessment of functional significance of stenotic lesions. We tried to evaluate the characteristics of CAD in dibetics by intravenous dipyridamloe (99m)Tc-MIBI(methoxy isobutyl isonitrile) SPECT(Single Photon Emission Computed Tomography). METHOD: (99m)Tc-MIBI SPECT and coronary arteriography(CAG) were performed simultaneously in less than 2 week interval in 41 diabetics(diabetic group) and 103 non-diabetics(non-diabetic group) with clinical suspicion of CAD. The sensitivity and specificity of (99m)Tc-MIBI SPECT for detection of CAD were compared between two groups. The site and number of involved vessels, the extent of perfusion defect and redistribution pattern were compared between two groups. RESULT: 1) The sensitivity and specificity of (99m)Tc-MIBI SPECT for detection of CAD were 97% and 80% in diabetics, these were comparable to those in non-diabetics(97% and 78%). 2) Three vessel disease were common(p<0.01)in diabetics(SPECT 28.1%, CAG 32.3%) than in non-diabetics(SPECT 11.4%, CAG 7.5%). Distal lesions were also more common(p<0.005) in diabetics(CAG 40.3%) than in non-diabetics(CAG 15.7%). 3) On stress SPECT, the extent of perfusion defect was not different in individual vessel areas between diabetics and non-diabetics. However the perfusion defect of left ventricle as a whole was significantly higher(p<0.05) in diabetics(35.2+/-16.2%) than in non-diabetics(26.4+/-15.5%). 4) On rest SPECT, the percent redistribution was significantly lower in diabetics than in non-diabetics(left anterior descending artery area ; diabetic group 31.1+/-22.5% vs non-diabetic group ; 49+/-28.5%, p<0.05, left ventricle as a whole ; diabetic group 30.6+/-21.2% vs non-diabetic group 48.2+/-27.6%, p<0.02). CONCLUSION: Quantitative (99m)Tc-MIBI SPECT provided high sensitivity and specificity for detection of CAD in diabetics. Multiple vessel disease, distal lesion and fixed lesions were more common in diabetics than in non-diabetics, (99m)Tc-MIBI SPECT is useful noninvasive test for diagnosis of CAD & important prognostic implications.

Myocardial Perfusion Imaging in Myocardial Infarction Using 99mTc-MIBI : A New Myocardial Imaging Agent

Technetium-99m methoxyisobutylisonitrile(99m-Tc MIBI), a new myocardial imaging agent, was used in myocardial perfusion scan in 23 patients who had been diagnosed as myocardial infarction to assess its usefulness in elvaluation of coronary artery disease. All patients undertook left ventriculography (LVG) and coronary arteriography (CAG). Gated blood pool scan, plannar scintigraphy and SPECT were also done using 99m-Tc MIBI. After then SPECT image was reconstructed to short axis view of the heart at the level of the base, mid and apex. The data from these studies were compared with the results of EKG, LVG and CAG. Diagnostic sensitivity of myocardial scan using 99m-Tc MIBI was 91.3%. In localization of infarction site and evaluation of its extent, myocardial scan was superior to EKG. CAG revealed significant stenosis at the arteries supplying the area in which the scan showed perfusion defect. In detecting abnormal wall motion, the sensitivity and the specificity were 81.9% and 93.7% respectively. Perfusion defect were found in 75%, 82.5%, and 100% of hypokinetic, akinetic, and dyskinetic segments, respectively. Myocardial perfusion scan using 99m-Tc MIBI was an useful noninvasive test in localizing the site and the extent of infarct and detecting the abnormal left ventricular wall motion.

LOCALIZATION OF PRIMARY HYPERPARATHYROIDISM WITH ~(99m)Tc-MIBI / 中华内分泌代谢杂志

Parathyroid scanning was performed with 99mTc-MIBI in 10 patients who had clinical and biochemical findings suggesting primary hyperparathyroidism but had no enlarged parathyroid or palpable thyroid. Seven cases were scanned with both 99mTc-MIBI and 99mTc and three cases with 99mTc-MIBI only but perchlorate was administered during the scan. A series of images were acquired for all cases at different time intervals after 99mTc-MIBI was injected intravenously to allow the dynamic studies. The P/T ratios (counts in parathyroid counts in thyroid)were also designed to see whether the agent had different uptakes and metabolic characteristics in parathyroid and thyroid tissues from 99mTc-MIBI. Surgical finding and histological examination were taken as gold standard against which US. CT and scintigraphy were judged. Finally, 10 adenomas found exactly at the sites predicted by scintigraphy and 2 hyperplastic glands were removed from the 10 patients. Ten of 10 99mTc-MIBI scans, two of 9 US scans and three of 8 CT scans were positive for a parathyroid adenoma, but 2 hyperplastic glands were missed by all of the three methods. It was shown that the suitable time for imaging was at 1h-2h or 30min-1h(if perchlorate was used) after 99mTc-MIBI was given, so as to render both adenoma and background clear. Despite the limited number of cases, the preliminary experience thus suggests that 99mTc-MIBI scintigraphy maybecome the technique of choice for the localization of hyperparathyroidism in stead of 21Tl.