Effects of nateglinide on myocardial microvascular reactivity in Type 2 diabetes mellitus--a randomized study using positron emission tomography.

AIMS: To evaluate effects of the oral antidiabetic insulinotropic agent nateglinide on myocardial blood flow (MBF) and microvascular reactivity in Type 2 diabetic patients. METHODS: Forty-seven Type 2 diabetic patients were randomly assigned 2 : 1 to nateglinide 120 mg (t.i.d., n = 33) or placebo (n = 14). At baseline and after 16 weeks of treatment, MBF was quantified using positron emission tomography with N-13 ammonia at rest, during endothelial-dependent stimulation by cold pressor test and during adenosine-mediated vasodilation. Additional blood samples were taken to assess glycaemic control and lipid profile. RESULTS: MBF at rest and during adenosine did not change during the study. The percentage of flow increase from rest during cold pressor test did not improve significantly in the nateglinide group vs. placebo (from 26.1 +/- 37.2% to 29.1 +/- 27.8% between week 0 to week 16 for nateglinide vs. 14.9 +/- 37.1% to 18.1 +/- 28.4% for placebo; P = 0.07 for nateglinide when adjusted for higher baseline values). Nateglinide decreased HbA1c by 0.4% (from 7.6 +/- 0.9% to 7.2 +/- 1.3%) compared to an increase of 0.5% in the placebo group (from 7.9 +/- 0.8% to 8.4 +/- 1.7%; P = 0.02 for nateglinide). No differences between the two groups were observed in insulin levels and lipid status. CONCLUSIONS: Nateglinide neither improved, nor impaired myocardial blood flow in Type 2 diabetic patients. Potential effects on endothelial-dependent myocardial blood flow remain to be investigated further. Positron emission tomography is a sensitive approach to assess the effects of therapeutic agents on myocardial blood flow in patients with diabetes.

Monitoring of tumour glucose metabolism by PET in a phase I study evaluating hormonal therapy in advanced pancreatic cancer.

BACKGROUND: Positron emission tomography (PET) determines therapy-induced changes in tumour glucose utilization. Experimental data indicate that cholecystokinin (CCK) stimulates pancreatic cancer growth. In this study in patients with advanced pancreatic cancer, we evaluated the use of fluorodeoxyglucose (FDG) PET compared with magnetic resonance imaging (MRI) in monitoring hormonal therapy using a highly selective, non-peptide CCK receptor antagonist (SR 27897B). METHODS: Nineteen patients were enrolled on a 28-day course of SR 27897B. Initially, 4 patients received 20 mg of SR 27897B; 9 patients received 40 mg; and 6 patients 80 mg. Imaging studies, including FDG-PET and MRI, were performed at baseline and on days 14 and 28. RESULTS: No significant changes in FDG uptake by the primary tumours were observed. Rate of progression of disease was 11 (61%) of 18 evaluable patients by MRI. Median survival of all patients enrolled was 2.7 months. SR 27897B was fairly well tolerated at all doses tested. The most common side effects were gastrointestinal disorders such as diarrhoea, flatulence and nausea. CONCLUSION: SR 27897B, when used alone at the limited doses employed, led neither to an impairment of tumour glucose metabolism nor to a reduction of tumour size in advanced pancreatic cancer.

99mTc-tetrofosmin SPECT for prediction of functional recovery defined by MRI in patients with severe left ventricular dysfunction: additional value of gated SPECT.

UNLABELLED: This study was designed to evaluate gated 99mTc-tetrofosmin SPECT for prediction of functional recovery proven by sequential MRI. 99mTc-labeled tetrofosmin is a recently introduced tracer for myocardial perfusion. However, its role for viability assessment is still under investigation. METHODS: 99mTc-tetrofosmin uptake in 19 patients with coronary artery disease and severe left ventricular dysfunction was correlated to regional wall thickening before and 4.5 +/- 0.8 mo after successful coronary artery bypass grafting, as derived from corresponding gated short-axis MRI. Preoperative wall thickening determined by gated SPECT was used as an additional parameter for prediction of functional outcome. Optimal threshold cutoffs to separate reversible from irreversible dysfunction were determined by receiver operator characteristic (ROC) analysis. RESULTS: The sensitivity and specificity of regional 99mTc-tetrofosmin for prediction of functional recovery was 87% and 42%, respectively (cutoff: 50% of maximum tracer retention). The area under ROC curves for prediction of functional recovery measured 0.66 +/- 0.01. Segments with > or =50% uptake and impaired but detectable wall thickening determined by gated SPECT had a significantly higher likelihood for functional improvement compared with segments with absent wall thickening (P < 0.05). There was no difference in segments with <50% tracer retention. There was good agreement for ejection fraction measurements by MRI and gated SPECT (mean ejection fraction 32 +/- 12 versus 34 +/- 11; r = 0.71, P < 0.001). CONCLUSION: Regional 99mTc-tetrofosmin uptake provided high sensitivity but limited specificity for prediction of functional recovery after revascularization, leading to fair overall accuracy. Wall thickening assessment derived from gated SPECT may improve the specificity of 99mTc-tetrofosmin uptake for prediction of functional recovery but not the sensitivity in low-flow areas. In addition to the assessment of global function, gated data acquisition can be helpful to improve the overall accuracy of 99mTc-tetrofosmin SPECT for prediction of functional recovery after bypass surgery.

Early recovery of coronary flow reserve after stent implantation as assessed by positron emission tomography.

OBJECTIVES: The aim of this study was to quantitatively evaluate myocardial flow reserve in patients early after coronary stent implantation using positron emission tomography. BACKGROUND: Delayed restoration of coronary flow reserve after percutaneous transluminal coronary angioplasty (PTCA) has been observed using a variety of techniques. Altered distal vasoregulation as well as residual stenosis have been considered possible explanations for this phenomenon. Although the implantation of stents may influence some of these mechanisms, little data are available characterizing coronary flow reserve early after stent placement. METHODS: In 14 patients 1.6 +/- 0.6 days after stenting, N-13-ammonia positron emission tomographic studies were performed at rest and during adenosine-induced vasodilation. Myocardial blood flow was quantified using a three-compartment model. Rest and stress flow data, as well as coronary flow reserve of stented vascular territories, were compared with that of remote areas. RESULTS: The stenosis decreased from 72.1 +/- 7.3% to 3.7 +/- 6.7% after stent implantation. Coronary flow in the stented areas did not differ significantly from that in remote areas either at rest (76.1 +/- 18.5 and 75.7 +/- 17.7 ml/min/100 g, respectively), or during maximal vasodilation (205.5 +/- 59.9 and 179.4 +/- 47.4 ml/min/100 g, respectively). In addition, there was no significant difference in the calculated values of coronary reserve of these two regions (2.74 +/- 0.64 and 2.43 +/- 0.55, respectively). CONCLUSIONS: The mechanical support of dilated arteries by a stent not only restores the macroscopic integrity of epicardial arteries, but also results, in contrast to conventional PTCA procedures, in early recovery of flow reserve.

Imaging of lung cancer with fluorine-18 fluorodeoxyglucose: comparison of a dual-head gamma camera in coincidence mode with a full-ring positron emission tomography system.

Dual-head gamma cameras operated in coincidence mode are a new approach for tumour imaging using fluorine-18 fluorodeoxyglucose (FDG). The aim of this study was to assess the diagnostic accuracy of such a camera system in comparison with a full-ring positron emission tomography (PET) system in patients with lung cancer. Twenty-seven patients (1 female, 26 males, age 62+/-9 years) with lung cancer or indeterminate pulmonary nodules were studied on the same day with a full-ring PET scanner (Siemens ECAT EXACT) and a coincidence gamma camera system (ADAC Vertex MCD). Sixty minutes after injection of 185-370 MBq FDG, a scan of the chest was performed with the full-ring system. Approximately 2 h p.i., the coincidence camera study was performed. Coincidence gamma camera (CGC) and PET images with (PETac) and without attenuation correction (PETnac) were analysed independently by two blinded observers. In addition, FDG uptake in primary tumours and involved lymph nodes was quantified relative to normal contralateral lung (T/L ratios). All primary tumours were histologically proven. The lymph node status was histologically determined in 23 patients. In four patients, no lymph node sampling was performed because of extensive disease or concurrent illnesses. In the 27 patients, 25 primary lung cancers and two metastatic lesions were histologically diagnosed. The number of coincidences per centimetre axial field of view was 3.33+/-0. 93x10(5) for the CGC and 1.09+/-0.36x10(6) for the dedicated PET system. All primary tumours (size: 4.6+/-2.6 cm) were correctly identified in the CGC and dedicated PET studies. T/L ratios were 4. 7+/-2.5 for CGC and 6.9+/-2.8 for PETnac (P <0.001). Histopathological evaluation revealed lymph node metastases in 11 of 88 sampled lymph node stations (size: 2.3+/-1.0 cm). All lymph node metastases were identified in the PETac studies, while PETnac detected 10/11 and CGC 8/11. For positive lymph nodes that were visible in CGC and PETnac studies, T/L ratios were 3.7+/-2.3 for CGC and 6.6+/-3.1 for PETnac (P=0.02). The diameters of false-negative lymph nodes in the CGC studies were 0.75, 1.5 and 2 cm. False-positive FDG uptake in lymph nodes was found in two patients with all three imaging methods. For all lesions combined, T/L ratios in CGC relative to PETnac studies decreased significantly with decreasing lesion size (r=0.62; P<0.001). In conclusion, compared with a full-ring PET system the sensitivity of CGC imaging for detection of lung cancer is limited by a lower image contrast which deteriorates with decreasing lesion size. Nevertheless, the ability of CGC imaging to detect pulmonary lesions with a diameter of at least 2 cm appears to be similar to that of a full-ring system. Both systems provide a similar specificity for the evaluation of lymph node involvement.

Myocardial perfusion scintigraphy to evaluate patients after coronary stent implantation.

UNLABELLED: Coronary stent implantation is an increasingly accepted revascularization method. The 20%-30% restenosis rate during the first 6 mo requires a close follow-up of the patients. Since there is very little data available defining the role of perfusion scintigraphy in the management of this population, the aim of this study was to assess the diagnostic performance of stress myocardial perfusion imaging for detecting restenosis in patients after coronary stent implantation. METHODS: In 82 patients, 93 rest or stress SPECT studies were performed using 201Tl and 99mTc-hexakis-2-methoxyisobutyl isonitrile to evaluate 99 vascular territories with implanted coronary stents. The average interval between the stent implantation and the scintigraphic study was 210.5 +/- 129.6 days. The scintiscans were visually evaluated. A stress-induced perfusion defect with reversibility at rest was used as the criterion for stent restenosis. RESULTS: Coronary angiography revealed a stenosis of > 50% diameter in the region of the stent in 19 arteries, while in 80 arteries there was no evidence of restenosis angiographically. With perfusion scintigraphy, 15/19 vascular territories with restenosed stents showed stress-induced perfusion abnormalities (sensitivity = 79%), while 62/80 territories without restenosis did not (specificity = 78%). In territories without a myocardial infarction (n = 48), sensitivity and specificity values were 8/8 (100%) and 36/44 (82%), and in territories with a myocardial infarction (n = 47) 7/11 (64%) and 26/36 (72%), respectively. Side branch stenosis was fairly frequent in patients without stent restenosis but with a reversible perfusion pattern on their scintiscan (8/18); however, these stenoses were induced infrequently by the stents (3 cases). CONCLUSION: Using the criterion of defect reversibility, stress perfusion SPECT can accurately detect restenoses of coronary artery stents. This method is most accurate for evaluating patients without a previous myocardial infarction in the stented vascular territory.

Regional myocardial wall thickening and global ejection fraction in patients with low angiographic left ventricular ejection fraction assessed by visual and quantitative resting ECG-gated 99mTc-tetrofosmin single-photon emission tomography and magnetic resonance imaging.

We investigated the use of visual and quantitative technetium 99m tetrofosmin ECG-gated single-photon emission tomography (SPET) for the assessment of regional myocardial wall thickening (WT) and left ventricular (LV) ejection fraction (EF) in comparison with gated magnetic resonance imaging (MRI) in patients with a low angiographic LVEF. Gated SPET using 99mTc-labelled flow tracers offers potential for simultaneous assessment of myocardial perfusion and LV function. Few data are available on the use of visual and quantitative gated SPET in patients with low LVEF. In this study 21 patients with low angiographic LVEF (mean 37%+/-5%) were studied. Resting gated 99mTc-tetrofosmin SPET and gated MRI were performed within 48 h. WT was assessed by visual interpretation (five point score) and quantitative analysis based on count increase. There was good agreement for EF measurements by MRI and gated SPET (mean EF: 33%+/-12% vs 35%+/-11%, r = 0.86, P<0.001). Areas under receiver operator characteristic curves (AUC) for differentiation between MRI WT score points ranged from 0.60 to 0.66 for visual SPET WT analysis, from 0.59 to 0.71 for delta count increase values and from 0.46 to 0.60 for % WT, indicating substantial overlap between WT categories. Absolute agreement for visual WT between MRI and gated SPET ranged from 25% to 57% (kappa 0.03-0.25) depending on tracer uptake, and was limited in areas with moderate to severe perfusion defects (kappa 0.03-0.13). It is concluded that gated SPET provided reliable estimates of regional WT and global function in patients with low angiographic LVEF.

Myocardial technetium-99m-tetrofosmin and technetium-99m-sestamibi kinetics in normal subjects and patients with coronary artery disease.

UNLABELLED: This study was designed to compare the tracer kinetics between 99mTc-sestamibi and 99mTc-tetrofosmin in a heterogeneous group of 24 patients admitted for routine perfusion imaging. METHODS: Twelve patients were studied with 99mTc-tetrofosmin and 12 with 99mTc-sestamibi. In each group, six patients had a low likelihood for coronary artery disease, and six patients had angiographically proven coronary artery stenoses of > 75% or previous myocardial infarction. Analysis of myocardial and liver uptake and clearance as well as target-to-organ contrasts were performed with planar stress images. RESULTS: Myocardial uptake of 99mTc-tetrofosmin was higher from 5 min (0.37 +/- 0.12 counts/pixel x MBq-1, p = 0.008) to 60 min (0.32 +/- 0.10 counts/pixel x MBq-1, p = 0.04) compared to 99mTc-sestamibi. Biological half-life for 99mTc-tetrofosmin (278 +/- 32 min) in normal myocardium was significantly shorter (p = 0.008) than for 99mTc-sestamibi (680 +/- 45 min). Biological liver half-life for 99mTc-tetrofosmin (67 +/- 16 min) was also significantly shorter (p = 0.02) than for 99mTc-sestamibi (136 +/- 18 min). Heart-to-lung ratios for 99mTc-tetrofosmin (2.49 +/- 0.43 at 5 min to 2.66 +/- 0.55 at 60 min) and 99mTc-sestamibi (2.52 +/- 0.37 at 5 min to 2.95 +/- 0.50 at 60 min) were similar. Whereas heart-to-liver ratios for 99mTc-tetrofosmin (1.04 +/- 0.24 at 5 min, increasing to 1.51 +/- 0.44 at 60 min) were significantly higher from 30-60 min postinjection (p = 0.05 at 30 min to p = 0.02 at 60 min) compared to the 99mTc-sestamibi (0.83 + 0.16 at 5 min to 1.08 +/- 0.27 at 60 min). CONCLUSION: Technetium-99m-tetrofosmin displays a shorter myocardial half-life compared to 99mTc-sestamibi. The rapid liver clearance of 99mTc-tetrofosmin, combined with comparable myocardial retention, resulted in higher heart-to-liver ratios but similar heart-to-lung contrasts compared to 99mTc-sestamibi from 30-60 min.