Technetium-99m Hexakis 2-methoxyisobutylisonitrile Research Articles

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

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 ((99m)Tc-MIBI) has been suggested as a tumor-seeking agent for the detection of MDR. The aim of this study was to evaluate (99m)Tc-MIBI single-photon emission computed tomography (SPECT)(/CT) for functional imaging of MDR-related and apoptosis-related proteins in patients with ovarian cancer. Eleven women (mean age 63 years, range 53-76) with a clinical suspicion of ovarian cancer were prospectively studied. All patients were examined with (99m)Tc-MIBI imaging before surgery. After intravenous injection of 740 MBq (99m)Tc-MIBI, SPECT(/CT) imaging at 10 min and 2 h was performed. Based on the semiquantitative analysis of (99m)Tc-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. (99m)Tc-MIBI imaging results and immunohistochemical results were compared. Laparotomy was performed in all patients. Six ovarian cancers were proven by histopathological examination. Five of the six ovarian cancers were positive for (99m)Tc-MIBI uptake on both early and delayed images with (99m)Tc-MIBI SPECT(/CT). MDR-related and apoptosis-related proteins were found to be expressed in all tumors. For the five positive (99m)Tc-MIBI uptake cases, the washout rate % of (99m)Tc-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). Our results suggested that (99m)Tc-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.

Interpretation of scintigraphic findings of oral malignant tumours with a new scanning agent of technetium-99m-hexakis-2-methoxy-isobutyl-isonitrile (Tc-99m-MIBI)

The purpose of this study was to investigate the usefulness of a new scanning agent of technetium-99m-hexakis-2-methoxy-isobutyl-isonitrile (Tc-99m-MIBI) for the diagnosis of malignant tumours of the head and neck. Scintigraphy with Tc-99m-MIBI was performed in 19 patients with malignant tumours of the head and neck. Factors of the early and delayed static scans (hot, warm or cold uptake), the early and delayed retention indexes, the blood flow index and the tumour retention index were obtained from Tc-99m-MIBI scintigraphy. Tumour retention indexes were classified into three grades; slightly (>0.9), moderately (0.9-0.8) and severely (0.8>) decreased. Grade of tissue differentiation of tumour (well, moderately or poorly differentiated) and tumour size (T1 approximately T4) were examined using the excised tumour. Scintigraphic indexes and tumour characteristics were compared. The early static scan and tumour size showed a correlation with the blood flow index. However, the delayed static scan did not show any relationship with blood flow index and tumour size. The tumour retention index had a tendency to decrease in malignant tumours, and showed a significant correlation with the grade of tissue differentiation of the tumour. The tendency of the tumour retention index to decrease in Tc-99m-MIBI scintigraphy showed the malignancy of tumour and would be useful for the diagnosis of malignant tumours of the head and neck.

Comparison using dynamic vectorcardiography and MIBI SPECT of ST-segment changes and myocardial MIBI uptake during percutaneous transluminal coronary angioplasty of the left anterior descending coronary artery

The quantitative relation between ST-segment changes and the severity and extent of myocardial ischemia during coronary occlusion remains unclear. This study assesses whether ST-segment changes during percutaneous transluminal coronary angioplasty (PTCA) correlate with the amount of myocardium at risk, measured with technetium-99m hexakis 2-methoxyisobutyl isonitrile (MIBI; also called sestamibi) single-photon emission computed tomography (SPECT). Quantitative continuous dynamic vectorcardiography was performed during PTCA of the left anterior descending coronary artery in 11 patients (mean age 64.3 years) without previous myocardial infarction. Change in the magnitude of the ST vector (STc-VM) was continuously recorded. A standardized protocol of balloon inflations was used and technetium-99m MIBI was injected intravenously at the onset of the third inflation. SPECT imaging was performed 60 minutes later and compared to a rest acquisition. SPECT was quantified by bull's-eye analysis using: (1) the change in the pathologic/normal area count ratio ( ΔP N ) as an index of the severity of ischemia; and (2) planimetered defect size during PTCA as an indicator of the size of the area at risk. The ΔP N from baseline to balloon occlusion (22 ± 11%) was correlated, albeit loosely, ta the maximum value of STc-VM (245 ± 186 μV, r = 0.62, p < 0.05), but there was no correlation between the size of the scintigraphic defect and STc-VM. Likewise, the sum of ST-segment elevation was correlated to ΔP N (r = 0.72, p < 0.02), but not ta the size of the scintigraphic defect. In conclusion, ST changes induced by coronary occlusion during PTCA are mostly related to the severity of ischemia rather than to the size of the area at risk. During coronary occlusion, ST changes provide only a crude estimate of the amount of jeopardized myocardium.

A non-invasive method for evaluating cirrhotic portal hypertension by administration of 99mTc-MIBI per rectum.

A study was performed to evaluate radio-isotopic imaging using technetium-99m hexakis 2-methoxyisobutyl isonitrile administered per rectum to assess portal collateral circulation. The heart-liver ratios (H/L; mean +/- standard deviation) in 15 controls, 13 cases of histologically confirmed viral hepatitis and 57 cirrhosis patients were 0.27 +/- 0.11, 0.43 +/- 0.14 and 1.00 +/- 0.28, respectively (P < 0.001). Among the cirrhosis patients those with the Child-Pugh classification A, B and C had H/L of 0.56 +/- 0.14, 1.00 +/- 0.20 and 1.19 +/- 0.26, respectively (P < 0.001). A high value of H/L was associated with a high risk of hepatic encephalopathy (1.25 +/- 0.17, P < 0.01) and oesophageal varices (1.02 +/- 0.20, P < 0.01). There were associations between H/L and serum bilirubin (P < 0.01), albumin (P < 0.05) and prothrombin time (P < 0.05). The results also showed a good correlation between H/L and portal vein pressure measured during operation in 13 patients (P < 0.001, r = 0.87). The regression equation: y = 6.77 + 32.5 H/L, allowed portal vein pressure to be estimated. The prognostic value of the test was supported by the fact that good correlations were observed between the H/L ratio and widely accepted prognostic classification (Child-Pugh). It is suggested that this new method could be a reliable non-invasive way to give an indication of the degree of portasystemic shunting to evaluate the prognosis and to follow up the effects of medications for reducing portal hypertension in patients with cirrhotic portal hypertension.

Simultaneous gallium-67 citrate and technetium-99m sestamibi SPET in a case of myocardial lymphoma: comparison with echocardiography before and after chemotherapy

A patient with diffuse large cell lymphoma involving the interventricular septum and the inferior ventricular wall was imaged with a simultaneous dual-isotope single-photon emission tomography (SPET) acquisition technique, using the radiotracers technetium-99m hexakis 2-methoxyisobutylisonitrile (sestamibi) and gallium-67 citrate, in conjunction with echocardiography, prior to and following the first course of chemotherapy. Simultaneous acquisition--with the advantage of displaying corresponding sets of SPET slices without any need for position correction--, supplemented by echocardiography, increased the accuracy of evaluation of the extent of disease and response to treatment.

Presurgical identification of hibernating myocardium by combined use of technetium-99m hexakis 2-methoxyisobutylisonitrile single photon emission tomography and fluorine-18 fluoro-2-deoxy-D-glucose positron emission tomography in patients with coronary artery disease.

We tested the possibility of identifying areas of hibernating myocardium by the combined assessment of perfusion and metabolism using single photon emission tomography (SPET) with technetium-99m hexakis 2-methoxyisobutylisonitrile (99mTc-MIBI) and positron emission tomography (PET) with fluorine-18 fluoro-2-deoxy-D-glucose (18F-FDG). Segmental wall motion, perfusion and 18F-FDG uptake were scored in 5 segments in 14 patients with coronary artery disease (CAD), for a total number of 70 segments. Each subject underwent the following studies prior to and following coronary artery bypass grafting (CABG): first-pass radionuclide angiography, electrocardiography gated planar perfusion scintigraphy and SPET perfusion scintigraphy with 99mTc-MIBI and, after 16 h fasting, 18F-FDG/PET metabolic scintigraphy. Wall motion impairment was either decreased or completely reversed by CABG in 95% of the asynergic segments which exhibited 18F-FDG uptake, whereas it was unmodified in 80% of the asynergic segments with no 18F-FDG uptake. A stepwise multiple logistic analysis was carried out on the asynergic segments to estimate the postoperative probability of wall motion improvement on the basis of the preoperative regional perfusion and metabolic scores. The segments with the highest probability (96%) of functional recovery from preoperative asynergy after revascularization were those with a marked 18F-FDG uptake prior to CABG. High probabilities of functional recovery were also estimated for the segments presenting with moderate and low 18F-FDG uptake (92% and 79%, respectively). A low probability of functional recovery (13%) was estimated in the segments with no 18F-FDG uptake.(ABSTRACT TRUNCATED AT 250 WORDS)

Area-at-risk determination by technetium-99m-hexakis-2-methoxyisobutyl isonitrile in experimental reperfused myocardial infarction.

In a canine model of reperfused myocardial infarction, we tested the hypothesis that after reperfusion, technetium-99m-hexakis-2-methoxyisobutyl isonitrile (Tc-MIBI) tomographic imaging still reflects occlusion blood flow when the tracer is injected before reperfusion. Nine anesthetized dogs underwent 2 hours of coronary occlusion followed by 3 hours of reperfusion ending by being killed. Reference coronary blood flow was determined by radioactive microspheres injected during occlusion and after reperfusion. Biopsies in normal and ischemic myocardium and single photon emission computed tomography were obtained during occlusion and after reperfusion. Circumferential profiles were applied to axial slices divided into 5-degree sectors. The sectors were divided into 3 groups selected on the occlusion acquisition (normal, mildly reduced, and severely reduced) and compared with the postreperfusion acquisition. Tissular Tc-MIBI kinetics was assessed both by Tc-MIBI time-activity curves of normal and ischemic tissue obtained by biopsy and by the relative gradient between normal, ischemic, and necrotic postmortem tissue samples. In biopsy samples, Tc-MIBI content remained unchanged during occlusion and after reperfusion in normal as well as in ischemic tissue (4,662 +/- 2,237 counts/min/mg vs. 4,599 +/- 1,577 counts/min/mg in normal tissue, NS; 941 +/- 903 counts/min/mg vs. 1,087 +/- 721 counts/min/mg in ischemic tissue, NS). In postmortem tissue samples, there was a good correlation between occlusion microsphere blood flow and Tc-MIBI activity (r = 0.91). In the necrotic samples, mean normalized Tc-MIBI activity (10 +/- 17%) was slightly higher than the normalized microsphere blood flow (3 +/- 3%, p less than 0.001) but markedly lower than the normalized microsphere reperfusion blood flow (63 +/- 31%, p less than 0.001). Comparing the single photon emission computed tomographic acquisitions before and after reperfusion, Tc-MIBI activity remained unchanged in normal as well as in mildly reduced or severely reduced segments. Thus, our data are consistent with the hypothesis that Tc-MIBI traces blood flow, does not redistribute significantly despite reperfusion, and can be used for imaging the area at risk.

Comparison of thallium-201 and technetium-99m hexakis 2-methoxyisobutyl isonitrile single-photon emission computed tomography for estimating the extent of myocardial ischemia and infarction in coronary artery disease

Single-photon emission computed tomography (SPECT) using thallium-201 (Tl-201) was compared with technetium-99m hexakis 2-methoxyisobutyl isonitrile (Tc-99m MIBI) in 24 patients with coronary artery disease. Patients exercised to the same work load as each isotope was studied. Normal and hypoperfused left ventricular mass was determined with an automated method. Estimated total left ventricular mass was similar for both stress/redistribution Tl-201 and stress/ rest Tc-99m MIBI images. The mean estimated defect size in the redistribution Tl-201 images was 32 ± 34.7 vs 33 ± 38.4 g in the resting Tc-99m MIBI studies (difference not significant). The individual determinations of defect mass were highly correlated (r = 0.93; p < 0.0001). Estimated defect size in the stress Tl-201 images (52 ± 46.2 g) was significantly larger than the exercise Tc-99m MIBI estimates of defect mass (42 ± 39.9 g; p < 0.05). A linear correlation existed between stress thallium and technetium estimates of defect size (r = 0.85) but 15 of 24 Tc-99m MIBI defects were smaller than the Tl-201 defects. Partial redistribution of Tc-99m MIBI could explain the discordance. Stress Tc-99m MIBI SPECT defect size determined by visual interpretation or by the use of isocount analysis may be smaller than what is seen with stress Tl-201 SPECT.

Single photon emission computed tomography with technetium-99m hexakis 2-methoxyisobutyl isonitrile in acute myocardial infarction before and after thrombolytic treatment: Assessment of salvaged myocardium and prediction of late functional recovery

Single photon emission computed tomography (SPECT) with technetium-99m hexakis 2-methoxyisobutyl isonitrile was investigated as a method to evaluate the results of intravenous thrombolytic treatment in 14 patients (11 men and 3 women) with acute myocardial infarction admitted to the coronary care unit within 4 h of the onset of symptoms. All patients received an injection of 740 MBq of the tracer before starting the thrombolytic therapy, and isonitrile tomography was performed 3 to 4 h later. The tomographic study was repeated 5 days after the acute event. The results of thrombolytic treatment were independently evaluated taking into account the clinical, electrocardiographic (ECG) and enzymatic data and the findings of left ventricular and coronary angiography. Furthermore, all patients were studied with two-dimensional echocardiography on admission, 5 days later and 1 month later. The site and extent of the perfusion defects on admission scintigraphy were consonant with the ECG and echocardiographic findings. A good correlation could be established between the 5 day scintigraphic estimate of infarct dimension and the enzymatic infarct size (r = 0.907, p less than 0.00002). The comparison between pre- and postthrombolytic treatment images enabled the identification of successful and unsuccessful reperfusion even in patients whose other noninvasive findings were inconclusive. Finally, the reduction in defect size predicted late functional improvement that was demonstrated by echocardiography performed 1 month later (r = 0.89, p less than 0.00005). The results of the study suggest the feasibility and the possible usefulness of isonitrile tomography in demonstrating the presence and size of myocardial damage and in assessing the extent of myocardial salvage after thrombolytic therapy in acute myocardial infarction.

Quantification of myocardial infarction during coronary occlusion and myocardial salvage after reperfusion using cardiac imaging with technetium-99m hexakis 2-methoxyisobutyl isonitrile

Myocardial imaging with technetium-99m hexakis 2-methoxyisobutyl isonitrile was investigated as a means to assess myocardial infarct size during coronary occlusion and to quantify the extent of salvaged myocardium after coronary occlusion followed by reperfusion. Open chest dogs underwent either a permanent coronary artery occlusion (Group 1, n = 16) or a 2 h occlusion followed by reperfusion (Group 2, n = 15). Animals in both groups were killed 48 h after occlusion. During coronary occlusion, 23 of the 25 dogs that survived the coronary occlusions had abnormal myocardial scintigrams. The scintigraphic perfusion defect size correlated well with the pathologic infarct size (r = 0.85 and 0.95 by planar and tomographic imaging, respectively). The planar scintigraphic defect size, but not the tomographic defect size, overestimated the pathologic size. The planar scintigraphic defect size observed during coronary occlusion was markedly reduced 48 h after reperfusion (24.8 +/- 12.8% to 10.6 +/- 9.7% of the left ventricle, p less than 0.003). The uptake of technetium-99m hexakis 2-methoxyisobutyl isonitrile in the ischemic myocardium increased significantly 48 h after reperfusion (p less than 0.003) and correlated with the increase in regional myocardial blood flow, as assessed by radioactive microspheres (r = 0.83, p less than 0.01). Thus, myocardial imaging with technetium-99m hexakis 2-methoxyisobutyl isonitrile allows reliable demonstration of the presence of acute infarction, estimation of infarct size and quantification of the extent of salvaged myocardium after coronary reperfusion.