Generation of Novel Anti-MUC1 Monoclonal Antibodies with Designed Carbohydrate Specificities Using MUC1 Glycopeptide Library.

Numerous anti-mucin 1 (anti-MUC1) antibodies that recognize O-glycan core structures have already been developed. However, most of them show low specificities toward O-glycan structures and/or low affinity toward a monovalent epitope. In this study, using an MUC1 glycopeptide library, we established two novel anti-MUC1 monoclonal antibodies (1B2 and 12D10) with designed carbohydrate specificities. Compared with previously reported anti-MUC1 antibodies, 1B2 and 12D10 showed quite different features regarding their specificities, affinities, and reactivity profiles to various cell lines. Both antibodies recognized specific O-glycan structures at the PDT*R motif (the asterisk represents an O-glycosylation site). 1B2 recognized O-glycans with an unsubstituted O-6 position of the GalNAc residue (Tn, T, and 23ST), whereas 12D10 recognized Neu5Ac at the same position (STn, 26ST, and dST). Neither of them bound to glycopeptides with core 2 O-glycans that have GlcNAc at the O-6 position of the GalNAc residue. Furthermore, 1B2 and 12D10 showed a strong binding to not only native MUC1 but also 20-mer glycopeptide with a monovalent epitope. These anti-MUC1 antibodies should thus become powerful tools for biological studies on MUC1 O-glycan structures. Furthermore, the strategy of using glycopeptide libraries should enable the development of novel antibodies with predesigned O-glycan specificities.

Correlation between late gadolinium enhancement and diastolic function in hypertrophic cardiomyopathy assessed by magnetic resonance imaging.

BACKGROUND: Diastolic dysfunction is common in patients with overt hypertrophic cardiomyopathy (HCM). Steady-state cine magnetic resonance imaging (MRI) enables measurement of the diastolic function of the left ventricle (LV), and late gadolinium enhanced MRI can delineate the presence and extent of fibrosis in HCM. The purpose of this study was to determine the relationship between the extent of myocardial fibrosis demonstrated by late gadolinium-enhanced MRI and diastolic dysfunction. METHODS AND RESULTS: Seventeen patients (13 men, mean age 57.7+/-9.8 years) with HCM were studied. The severity index of late gadolinium enhancement was determined by scoring the extent of enhanced tissue in 30 myocardial segments. The peak filling rate (PFR), LV ejection fraction and LV mass were determined by cine MRI. Contrast-enhanced MRI demonstrated late gadolinium enhancement in 97 of 510 segments (19%) and 13 of the 17 patients (77%). The severity index of late gadolinium enhancement demonstrated a significant negative correlation with PFR (r= -0.86, p<0.01) and with the LV ejection fraction (r= -0.59, p<0.05). No significant correlation was observed between the severity index of late gadolinium enhancement and LV mass (r=0.23, p=0.30). CONCLUSION: The extent of myocardial fibrosis revealed by late gadolinium-enhanced MRI has a strong relationship to diastolic dysfunction in patients with HCM.

Thallium-201 SPECT and low-dose dobutamine stress cine MRI for predicting functional recovery of regional myocardial contraction in patients with myocardial infarction.

OBJECTIVES: The purpose of this study was to compare the diagnostic performances of Tl-201 single photon emission computed tomography (SPECT) and dobutamine stress cine magnetic resonance imaging (MRI) for predicting functional recovery of regional myocardial contraction in patients after myocardial infarction. METHODS: Twenty patients underwent Tl-201 SPECT and MRI 3-4 weeks after onset of myocardial infarction. Cine MR images were acquired in the resting state and during dobutamine stress. Tl-201 uptake and systolic wall thickening (SWT) on cine MRI were analyzed on short-axis images by using a 14-segment model. Follow-up cine MR images were obtained 187.1+/-33.5 days after onset. RESULTS: The averaged Tl-201 uptake in 54 segments with impaired SWT was 47%+/-20%, being significantly lower than that in 226 segments with preserved SWT (75%+/-18%; p<0.0001). The sensitivity, specificity, and accuracy of dobutamine MRI and Tl-201 SPECT for predicting preserved SWT after 6 months were 89% vs. 80%, not significant (NS); 89% vs. 72%, p<0.01; and 89% vs. 79%, NS, respectively. In the anterior wall and apex, the sensitivity and specificity of SPECT were not significantly different from those of MRI. In the inferior wall and posterolateral wall, however, the specificity of SPECT was substantially lower than that of MRI (53% vs. 88%, p<0.001), resulting in significantly lower accuracy (75% vs. 90%, p<0.01). CONCLUSIONS: Both SPECT and dobutamine MRI showed excellent sensitivity for predicting myocardial viability in all left ventricular segments. Decreased specificity of SPECT in the inferior and posterolateral segments resulted in lower overall specificity in comparison with dobutamine MRI.

Prediction of regional functional recovery after acute myocardial infarction with low dose dobutamine stress cine MR imaging and contrast enhanced MR imaging.

PURPOSE: Previous studies demonstrated that low-dose dobutamine stress cine magnetic resonance imaging (MRI) and delayed contrast-enhanced MRI can provide assessments of myocardial viability. The purpose of this study was to evaluate the comparative diagnostic values of dobutamine cine MRI and delayed contrast-enhanced MRI for predicting functional recovery of myocardial contraction in patients with acute reperfused myocardial infarction. METHODS: Twenty-three patients with myocardial infarction after percutaneous coronary interventions were studied. All patients underwent steady-state cine MRI covering the entire left ventricle at rest and during low-dose dobutamine stress (10 micrograms/kg/min). Delayed contrast-enhanced MR images were acquired to determine transmural extent of hyperenhancement. Second cine MR images in the resting state were obtained 3 to 11 months after revascularization. RESULTS: On the first cine MR images in the resting state, 278 (20%) of 1380 segments demonstrated abnormal, regional contraction (systolic wall thickening < 40%). Of the 175 segments showing functional recovery on the following cine MRI, 156 (89%) segments were recognized as reversible by dobutamine cine MRI and 146 (83%) segments by delayed contrast-enhanced MRI. The sensitivity, specificity, and accuracy of dobutamine stress cine MRI was 89%, 80%, and 86%, respectively. These values of contrast-enhanced MRI were 83%, 72%, and 79%, respectively. The area under the receiver operating curve (ROC) was 0.87 by dobutamine cine MRI and 0.78 by delayed contrast-enhanced MRI (p < 0.05). CONCLUSIONS: The current results using quantitative segmental analysis indicated that low-dose dobutamine stress cine MRI can predict recovery of myocardial contractility with significantly higher diagnostic performance in comparison with contrast-enhanced MRI in patients with myocardial infarction who underwent revascularization.

Evaluation of left ventricular volumes and ejection fraction using fast steady-state cine MR imaging: comparison with left ventricular angiography.

Previous studies demonstrated that magnetic resonance (MR) imaging consistently underestimated angiographic measurements of left ventricular (LV) volumes. The purpose of this study was to determine whether MR imaging with steady-state free precession acquisition (SSFP) can provide improved accuracy and reproducibility in measuring cardiac function in comparison with fast spoiled gradient echo cine MR imaging (SPGR). Twenty patients with cardiovascular diseases who underwent breath-hold cine MR imaging within one week of LV angiography were studied. Two sets of breath-hold cine MR images were obtained, one with SSFP and another with SPGR. The LV volumes determined by two breath-hold cine MR sequences were compared with the results by LV angiography. SPGR cine MR imaging consistently underestimated angiographic LV volumes. The mean difference of LV end-diastolic volume was -22.5 +/- 14.8 ml (p < 0.001) for short-axis planes and -27.7 +/- 21.5 ml (p < 0.001) for long-axis planes. In contrast, LV volumes measured by the SSFP imaging showed a good agreement with the results by angiography. The mean difference of LV end-diastolic volume was -2.5 +/- 14.3 ml (p = N.S.) for short-axis planes and -10.9 +/- 15.1 ml (p < 0.01) for long-axis planes. Standard error of the estimation in measuring LV end-diastolic volume with the SSFP imaging was 3.9% for short-axis images and 4.9% for long-axis images. These values were 7.2% and 8.7% with the SPGR imaging. In conclusion, the SSFP acquisition can provide accurate and noninvasive assessments of LV volumes and ejection fraction within a reduced imaging time.