Search

The aim of this study was to assess, by positron emission tomography (PET), the effect on cerebral functional activity of a new lorazepam-γ-aminobutyric acid (GABA) conjugate [3-(4-acetamido)-butyrril lorazepam (DDS2700)]. Ten healthy volunteers were studied by PET and [ 18 F]fluoro-deoxy-D-glucose ([ 18 F]FDG) under baseline conditions and following the administration of DDS2700. Regional cerebral blood flow (rCBF) was measured by PET and 15 O-water in three additional participants while they performed attentive tasks, before and after drug administration. DDS2700 induced a decrease in the regional cerebral metabolic rate of glucose (rCMRglu) in the thalamus (-17%), cerebellum (-11%) and caudate nucleus (-8%). The observed effects on glucose metabolism were probably related to the subjective sedation and tiredness reported by the participants. During the attentive tasks, rCBF increased in frontal and temporal regions associated with attentional processing of auditory material. These circuits were no longer active after DDS2700 administration, while rCBF increased in cingulate cortex, occipitoparietal regions, pons and cerebellum. These drug-induced activations might be directly related to intervening sleepiness and to the consequent effort in keeping attention focused on the tasks. The effects of DDS2700 on glucose metabolism at rest, and on rCBF during activation conditions, indicate a drug action on cerebral networks involved in alertness, vigilance and attention maintenance. PET assessment by [ 18 F]FDG and water may provide complementary information in pharmacodynamic studies.

The use of 201Tl has been proposed for the differential diagnosis of lymphomas and non-neoplastic brain masses in AIDS patients. The aim of this study was to assess the diagnostic accuracy of three different semi-quantitative methods for the analysis of 201Tl SPET brain images in individuals with AIDS and brain lesions. Thirty-seven AIDS patients with contrast-enhancing brain lesions underwent 201Tl SPET. Three different lesion-to-background uptake indices were calculated: (1) small lesion/large background (SL/ LB; i.e. counts in a 3 × 3 pixel ROI in the lesion/counts in a 7 × 7 pixel ROI in the contralateral healthy hemisphere); (2) small lesion/multiple small background (SL/MSL; i.e. counts in a 3 × 3 pixel ROI in the lesion/average counts of ten 3 × 3 ROIs over the highest background pixel values); (3) large lesion/large background (LL/LB; i.e. counts in an elliptic ROI in the lesion/counts in a contralateral mirrored ROI). Data analysis included a ROC curve analysis to identify the cut-off value corresponding to the highest accuracy value, and an analysis of the predictive value to classify the patients in three categories (high, intermediate and low risk of lymphoma). The greatest accuracy (71%) was achieved with the LL/LB method of analysis. Using this method, 62% of patients could be classified as either having lymphoma or not, whereas 38% could not be classified. LL/LB values ≥ 2.9 are suggestive of the presence of lymphomas, whereas values ≤ 2 are highly predictive of the presence of a lesion other than lymphoma. However, LL/LB values between 2 and 3 are not diagnostic and adjunctive tests should be carried out. In conclusion, 201Tl SPET was an adequate diagnostic tool in approximately 70% of the cases in this study. © 1997 Chapman and Hall Ltd.

We studied the relationships between coronary anatomy, perfusion and metabolism in myocardial segments exhibiting transient and persistent perfusion defects on stress/rest 99Tcm-MIBI single photon emission tomography in 35 patients (31 males, 4 females, mean age 56 ± 7 years) with a previous myocardial infarction. Quantitative coronary angiography and assessment of myocardial perfusion reserve and glucose metabolism were performed within 1 week of one another. Perfusion was assessed by SPET after the intravenous injection of 740 MBq of 99Tcm-MIBI at rest and after exercise. Regional myocardial glucose metabolism was assessed by position emission tomography at rest (200 MBq of 18F-2-deoxyglucose, FDG) after an overnight fast with no glucose loading. All 35 patients exhibited persistent perfusion defects consistent with the clinically identified infarct site, and 27 (77%) also showed various degrees of within-infarct FDG uptake; 11 patients developed exercise-induced transient perfusion defects within, or in the vicinity of, 15 infarct segments and resting FDG uptake was present in 10 of these segments (67%). Five patients also showed exercise-induced transient perfusion defects in nine segments remote from the site of infarct: resting FDG uptake was present in six of these regions (67%). Finally, nine patients had increased glucose uptake in non-infarcted regions not showing transient perfusion defects upon exercise—testing and perfused by coronary arteries with only minor irregularities. Our results confirm the presence-of viable tissue in a large proportion of infarct sites. Moreover, FDG uptake can be seen in regions perfused by coronary arteries showing minor irregularities, not necessarily resulting in detectable transient perfusion defects on a MIBI stress scan. Since the clinical significance of such findings is not clear, further studies should be conducted to assess the long-term evolution of perfusion, function and metabolism in non-revascularized patients of those remote areas which are apparently normally perfused, but show abnormal fasting FDG uptake after myocardial infarction. Such studies may have important implications for the management of post-infarct patients, as the preservation of coronary vasodilator reserve and myocardial metabolism in remote myocardium may be seen as an additional goal in the treatment of such patients. © 1998 Lippincott-Raven Publishers.

There have been a number of indications that sex hormones can affect the rate of growth of meningiomas during pregnancy. The presence of oestrogen or progesterone receptors in meningiomas and the influence of sex hormones upon cell cultures derived from human meningiomas have been extensively investigated. The results have been controversial, with most of the discussion centring upon the presence and possible role of oestrogen receptors. The aim of the present study was to assess oestrogen receptors in human meningiomas with 16α[ 18 F]fluoro-17β-oestradiol ([ 18 F]FES) and positron emission tomography (PET). With this purpose in mind, we measured the regional brain uptake of [ 18 F]FES in six patients with a neuroradiological and histological diagnosis of meningioma, comparing the in vivo PET data with the immunohistological analysis of oestrogen receptors performed on formalin-fixed, paraffin-embedded tissue obtained at surgery. Two analyses were used for the in vivo measurement of [ 18 F]FES binding to oestrogen receptors: the ratio of tumour activity to that of normal tissue (T/NT), calculated 90 min after tracer injection, and the ratio between the equilibrium distribution volume (DV) in normal and pathological tissues, calculated by means of a graphical kinetic analysis. PET studies demonstrated a marked uptake of [ 18 F]FES by the tumour in four of the six patients. Immunohistochemical assay using a manual staining method capable of detecting oestrogen receptors at a level of > 10 pmol mg -1 of protein detected only sparse immunostaining in one of the six meningiomas. Distinct albeit weak immunostaining was demonstrated in five of the six meningiomas when the sensitivity of the immunohistochemical assay was increased to < 10 pmol mg -1 of protein by use of an automated staining method (Bioteck 1000). Comparison of the in vivo and immunohistochemical results showed a correlation in five of the six patients, thus indicating the high sensitivity of [ 18 F]FES for the in vivo evaluation of oestrogen receptor expression.

In previously thrombolysed patients, we analysed residual myocardial viability using the PET-FDG technique and correlated its presence and extent to the angiographic appearance of the infarct-related vessel and left ventricular function. Thirty-six patients who had undergone intravenous thrombolysis for acute myocardial infarction 4.8 +/- 7.2 months previously were studied. Coronary angiography, left ventriculography, and assessment of myocardial perfusion and metabolism were all performed within 1 week. All patients exhibited perfusion defects consistent with the clinically identified myocardial infarction site. Residual viability, as assessed by the PET-FDG technique, was present in 53% of cases. The infarct-related coronary artery was patent in 19 (53%) patients (TIMI grade 3, 79%); of the remaining 17 with occluded infarct-related arteries, 11 had collaterals to the infarct area. Significant FDG uptake was observed in 63% of patients with a patent infarct-related artery and in 41% of those with an occluded infarct-related artery. The same study protocol was adopted in a control group of 30 patients with myocardial infarction who did not receive thrombolysis. The number of infarct-related patent vessels was significantly lower in these patients (30 vs 53%) (TIMI grade 3, 56%), but the overall percentage of PET viability was again 53%. Qualitative analysis of the regional perfusion pattern showed that the magnitude and severity of the perfusion defect was similar in the two groups, regardless of the presence or absence of FDG uptake. Global left ventricular function was also similar in the two groups. However, regional wall motion was significantly better in the thrombolysed patients with a patent infarct-related artery than in those who had not received thrombolysis and whose culprit vessel was also patent. In conclusion, the results of our study support the notion that early recanalization of the infarct-related artery is critical for preserving left ventricular function. Although the number of patent infarct-related coronary arteries is greater and left ventricular function is better in successfully thrombolysed patients, the regional metabolic pattern does not apparently correlate with the patency of the infarct-related artery. This suggests that, in 'chronic' myocardial infarction, residual tissue viability as assessed by fluorodeoxyglucose uptake does not necessarily correlate with coronary recanalization. RI Lucignani, Giovanni/C-6773-2008

The relationships between rest conditions of myocardial asynergy, response to dobutamine administration, perfusion and glucose metabolism were examined in 12 patients with chronic coronary artery disease and left ventricular dysfunction. We evaluated (1) rest and stress myocardial perfusion by 99 Tc m -methoxyisobutylisonitrile (MIBI) and single photon emission tomography (SPET), (2) rest myocardial segmental wall motion by trans-thoracic echocardiography and low-dose dobutamine, and (3) myocardial metabolism by [ 18 F]-2-fluoro-2-deoxy-D-gyucose ( 18 FDG) and positron emission tomography (PET), in the fasting state. The analysis was carried out on 16 left ventricular myocardial segments. The SPET studies were analysed semi-quantitatively by normalization to the peak activity. Wall motion was assessed by a visual score. An 18 FDG index was determined as the tissue/blood pool radioactivity ratio in each segment. The results showed: (1) remarkably good agreement between the number of dobutamine responsive segments and 18 FDG positive segments among those that were only moderately hypoperfused and hypokinetic; (2) a smaller number of dobutamine responsive segments than 18 FDG positive segments among those that were hypoperfused and akinetic; and (3) the presence of 18 FDG in 50% of the segments that were severely hypoperfused and akinetic or dyskinetic and without improvement with dobutamine. These results indicate that in severely hypoperfused and akinetic or dyskinetic segments, trans-thoracic echocardiography under inotropic stimulation provides little additional information compared with that obtained with rest echocardiography and perfusion studies; the assessment of 18 FDG uptake provides information that is complementary to that obtained by perfusion assessment, rest and dobutamine trans-thoracic echocardiography.

The relationship between severity of coronary artery stenosis (CAS) and myocardial 18F-2-fluoro-2-deoxy-D-glucose (18F-FDG) uptake in the fasting state, assessed with positron emission tomography (PET), was examined in a series of 48 patients with CAS undergoing both studies for diagnostic purposes. The data analysis was based on the subdivision of the left ventricular myocardium into four segments defined in relation to ventricular vascularization: the anterior and septal segments, perfused by the left anterior descending artery; the lateral segment, perfused by the left circumflex; and the inferior segment, perfused by the right coronary artery. The 192 segments were grouped according to degree of CAS: I 0-50%, II 51-75%; III 76-90%; IV 91-99%; V and VI occluded coronary artery with good or poor collaterals, respectively. An 18F-FDG index was determined as the tissue/blood pool radioactivity ratio in each segment. The statistical analysis was performed by one-way ANOVA, multiple comparison tests and the chi-squared test. The proportion of segments with 18F-FDG uptake was also analysed for a linear trend across the ordered levels of CAS. The 18F-FDG index in groups I to V was significantly higher than in controls, but it was not different among the groups with CAS, except for group V versus I. However, the proportion of segments with enhanced 18F-FDG uptake was correlated to the degree of CAS. In cases of complete occlusion of a major afferent coronary artery, the proportion of segments with 18F-FDG uptake varied in relation to the presence of collaterals.(ABSTRACT TRUNCATED AT 250 WORDS)