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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 These circuits were no longer active after DDS2700 administration, while rCBF increased in cingulate cortex, occipitoparietal regions, pons and cerebellum.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 [18F]fluorodeoxyglucose ([18F]FDG) method for measuring brain metabolism has not the wide clinical application that one might expect, partly because of its high cost and the complexity of the quantification procedure, but also because of reporting techniques based on region of interest (ROI) analysis, which are time-consuming and not fully objective. In this paper we report a clinical validation of statistical parametric mapping (SPM) using rCMRglc (quantitative) and radioactivity distribution (nonquantitative) [18F]FDG PET data. We show that a 10-min noninteractive voxel-based SPM analysis on a standard workstation enables objective assessment, including localization in stereotactic space, of regional glucose consumption abnormalities, whose reliability can be assessed on statistical and clinical grounds. Clinical validity was established using a small series of patients with degenerative or developmental disorders, including probable Alzheimer's disease, progressive aphasia, multiple sclerosis, developmental specific language impairment, and epilepsy. Analysis of quantitative and nonquantitative data showed the same pattern of results, suggesting that, for clinical purposes, quantitation and invasive arterial cannulation can be avoided. This should facilitate a wider application of the technique and the extension of SPM clinical analysis to H215O PET or high resolution SPECT perfusion 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.

Cerebral PET with [18F]-2-fluoro-2-deoxy-D-glucose has been performed in four patients with neurofibromatosis type 1 (NF1) to assess the relation between cerebral metabolic activity, MRI, and the presence of neurological symptoms, including seizures, as well as mental and language retardation. Widespread hypometabolism occurred in three of the patients. The lesions on MRI, which were localised in the subcortical white matter and grey structures, had normal rates of glucose metabolism. This finding suggests that the abnormalities seen on MRI are not due to defective blood supply, localised oedema, or grey matter heterotopic foci as previously hypothesised. The presence of the hypometabolic areas seems to be inconsistently related to the occurrence of seizures and is not proportional to the degree of mental impairment. This study provides evidence of a widespread cerebral hypometabolism that is not related to the presence of MRI abnormalities; conversely normal metabolism was present in the areas with an abnormal MRI signal.

Purpose To perform a cost analysis between vacuum-assisted percutaneous nephrolithotomy (vmPCNL) and minimally invasive PCNL (MIP) and explore potential predictors of costs associated with the procedures. Methods We analyzed data from 225 patients who underwent vmPCNL or MIP at a single tertiary referral academic center between January 2016 and December 2020. We collected patients’ demographics, peri-and postoperative data and detailed expense records. After propensity score matching, 108 (66.7%) vmPCNL and 54 (33.3%) MIP procedures were analyzed. Descriptive statistics assessed differences in clinical and operative parameters. Univariable and multivariable linear regression models tested the association between clinical variables and costs. Results Operative time (OT) was shorter for vmPCNL, and the use of additional instruments to complete litholapaxy was more frequent in MIP (all p ≤ 0.01). Length of stay (LOS) was longer for MIP patients (p = 0.03) and the stone-free (SF) rate was higher after vmPCNL (p = 0.04). The overall instrumentation cost was higher for vmPCNL (p p = 0.9). However, the overall cost for the hospitalization was higher for MIP than vmPCNL (p = 0.01). Univariable linear regression revealed that patient’s comorbidities, OT, any postoperative complication and LOS were associated with hospitalization costs (all p p Conclusion vmPCNL may represent a valid option due to clinical and economic benefits. Shorter OT, the lower need for disposable equipment and the lower complication rate reduced procedural and hospitalization costs.

The cerebral distribution of 99mTc-labeled d, l, hexamethyl-propylene-amine-oxime (99mTc-HMPAO) as a function of rCBF and time was examined in rats and in man. The results of this study confirm that 99mTc-HMPAO is distributed in brain in proportion to rCBF. However, the rapid systemic breakdown of the tracer in blood results in considerable difficulties in the assessment of the arterial concentration of the parent compound; incomplete extraction of 99mTc-HMPAO from blood to brain and significant efflux from brain represent further limitations in the use of this tracer for quantification of rCFB. Despite these limitations 99mTc-HMPAO is of potential interest for a qualitative assessment of rCBF in specific clinical conditions.

We used [18F]2-fluoro-2-deoxy-D-glucose ([18F]FDG) and positron emission tomography (PET) to study regional cerebral glucose utilization (rCMRglc) in four patients with fatal familial insomnia (FFI), a prion disease with a mutation at codon 178 of the prion protein gene. Two patients, presenting only with insomnia and dysautonomia, had a prominent and, in one case, selective thalamic hypometabolism. The remaining two cases presented a more complex clinical picture with multiple neurologic deficits, with both thalamic and widespread brain hypometabolism involving the majority of cortical structures, basal ganglia, and the cerebellum. This widespread pattern was present in the early stage of the disease and showed significant worsening as the disease progressed in one patient examined twice. The thalamic hypometabolism, consistently found with PET in FFI patients, is in agreement with the neuropathologic findings and is a hallmark of the disease.

Amyotrophic Lateral Sclerosis (ALS) is a progressive neurodegenerative disease characterized by degeneration of both upper and lower motor neuron located in the spinal cord and brainstem. Diagnosis of ALS is predominantly clinical, nevertheless, electromyography and Magnetic Resonance Imaging (MRI) may provide support. Several advanced MRI techniques have been proven useful for ALS diagnosis and, indeed, the combination of different MRI techniques demonstrated an improvement in sensitivity and specificity as far as 90%. This review focus on the imaging techniques currently used in the diagnosis and management of ALS with brief considerations on future applications.

Regional cerebral and cerebellar blood flows were studied by N, N, N'-trimethyl- N'-(2-hydroxy-3-methyl-5-[123I]iodobenzyl)-1,3-propanediamine 2 HC1 (1-123 HIPDM) and single-photon emission computerized tomography (SPECT) in a patient with an ischemic lesion of the pons. An asymmetry of perfusion of the cerebellar hemispheres, normal on transmission computerized tomography scan, was demonstrated by SPECT studies in the early acute phase and confirmed 15 days after. This finding may be related to the interruption of the corticopontocerebellar pathways.

The remote effects of small unilateral cerebrovascular lesions confined to subcortical structures were evaluated by single photon emission computerized tomography (SPECT) and a CBF tracer, I-123 HIPDM. A CBF study was performed in 34 patients presenting with subcortical stroke either in the acute or in the chronic stages. Twenty-one of the 34 patients showed areas of cortical hypoperfusion ipsilateral to the subcortical lesion. In 14 patients, asymmetry of perfusion was also observed at the cerebellar level, perfusion being significantly reduced in the cerebellar hemisphere contralateral to the lesion. There was no correlation between the degree and extension of these remote effects and the type of stroke (ischemic or hemorrhagic), the patency of cerebral arteries, or the size and site of the lesion by transmissive computerized tomography (TCT). Subcortical hematomas showed a correlation between occurrence of remote effects and time interval from the onset of stroke, occurring more frequently in the acute phase. A correlation was observed between cortical and cerebellar remote effects and the severity of clinical presentation. The causes of remote effects are still unclear and have been extensively debated. Our data indicate that there is a relationship of remote effect to the neurological status. It is possible to show, by noninvasive, low-cost methods, remote CBF effects after stroke that may contribute to the assessment of brain functional impairment.

Purpose: Hypoxia-inducible factor 1α (HIF-1α) activity is one of the major players in hypoxia-mediated glioma progression and resistance to therapies, and therefore the focus of this study was the evaluation of HIF-1α modulation in relation to tumour response with the purpose of identifying imaging biomarkers able to document tumour response to treatment in a murine glioma model. Methods: U251-HRE-mCherry cells expressing Luciferase under the control of a hypoxia responsive element (HRE) and mCherry under the control of a constitutive promoter were used to assess HIF-1α activity and cell survival after treatment, both in vitro and in vivo, by optical, MRI and positron emission tomography imaging. Results: This cell model can be used to monitor HIF-1α activity after treatment with different drugs modulating transduction pathways involved in its regulation. After temozolomide (TMZ) treatment, HIF-1α activity is early reduced, preceding cell cytotoxicity. Optical imaging allowed monitoring of this process in vivo, and carbonic anhydrase IX (CAIX) expression was identified as a translatable non-invasive biomarker with potential clinical significance. A preliminary in vitro evaluation showed that reduction of HIF-1α activity after TMZ treatment was comparable to the effect of an Hsp90 inhibitor, opening the way for further elucidation of its mechanism of action. Conclusion: The results of this study suggest that the U251-HRE-mCherry cell model can be used for the monitoring of HIF-1α activity through luciferase and CAIX expression. These cells can become a useful tool for the assessment and improvement of new targeted tracers for potential theranostic procedures.

Characterisation of the physical performance of the new integrated PET/CT system Discovery ST (GE Medical Systems) has been performed following the NEMA NU 2-1994 (N-94) and the NEMA NU 2-2001 (N-01) standards in both 2D and 3D acquisition configuration. The Discovery ST combines a four or eight multi-slice helical CT scanner with a PET tomograph which consists of 10,080 BGO crystals arranged in 24 rings. The crystal dimensions are 6.3 x 6.3 x 30 mm(3) and they are organised in blocks of 6 x 6 crystals, coupled to a single photomultiplier tube with four anodes. The 24 rings of the PET system allow 47 images to be obtained, spaced by 3.27 mm, and covering an axial field of view of 157 mm. The low- and high-energy thresholds are set to 375 and 650 keV, respectively. The coincidence time window is set to 11.7 ns. Using the NEMA N-94 standard, the main results were: (1) the average (radial and tangential) transverse spatial resolution (FWHM) at 1, 10 and 20 cm off axis was 6.28 mm, 7.09 mm and 7.45 mm in 2D, and 6.68 mm, 7.72 mm and 8.13 mm in 3D; (2) the sensitivity for true events was 8,567 cps/kBq/cc in 2D and 36,649 cps/kBq/cc in 3D; (3) the scatter fraction was 15% in 2D and 30% in 3D; (4) the peak true events rate, the true events rate at 50% of the system dead-time and the true events rate when equal to the random events rate were 750 kcps at 189.81 kBq/cc, 744 kcps at 186.48 kBq/cc and 686 kcps at 150.59 kBq/cc, respectively, in 2D, and 922 kcps at 44.03 kBq/cc, 834 kcps at 53.28 kBq/cc and 921 kcps at 44.03 kBq/cc in 3D; (5) the noise equivalent count (NEC) peak rate was 270 kcps at 34.38 kBq/cc in 3D, with random coincidences estimated by delayed events. Using the NEMA N-01 standards the main results were: (1) the average transverse and axial spatial resolution (FWHM) at 1 cm and 10 cm off axis was 6.28 (4.56) mm and 6.88 (6.11) mm in 2D, and 6.29 (5.68) mm and 6.82 (6.05) mm in 3D; (2) the average sensitivity for the two radial positions (r=0 cm and r=10 cm) was 1.93 cps/kBq in 2D and 9.12 cps/kBq in 3D; (3) the scatter fraction was 19% in 2D and 45% in 3D; (4) the NEC peak rate was 54 kcps at 46.99 kBq/cc in 2D and 45.5 kcps at 10.84 kBq/cc in 3D, when random coincidences were estimated by using k=2 in the NEC formula, while the NEC peak rate was 81 kcps at 64.43 kBq/cc and 66 kcps at 14.86 kBq/cc in 2D and 3D, respectively, when random coincidences were estimated by using k=1 in the NEC formula. The new integrated PET-CT system Discovery ST has good overall performances in both 2D and 3D, with in particular a high sensitivity and a very good 3D NEC response.

This study investigates the effect of chronic treatment with Fluvoxamine, a potent and specific serotonin reuptake sites inhibitor (SSRI), on 5HT(2) serotonin and D(2) dopamine receptors in the brain of drug naive unipolar depressed patients. Drug effect was evaluated in different cortical areas and in the basal ganglia by positron emission tomography (PET) and fluoroethyl-spiperone ([(18)F]FESP), an high affinity 5HT(2) serotonin and D(2) dopamine receptors antagonist. Patients underwent a PET study at recruitment and after clinical response to Fluvoxamine treatment. Nine of the 15 patients recruited completed the study. Fluvoxamine treatment significantly improved clinical symptoms and modified [(18)F]FESP binding in the frontal and occipital cortex of all of the nine patients who completed the study; in these regions a mean 31% increase in the in vivo [(18)F]FESP binding was found (P < 0.01). On the contrary, no significant changes in the in vivo [(18)F]FESP binding were found in the basal ganglia where [(18)F]FESP binds mainly to D(2) dopamine receptors. Chronic treatment with Fluvoxamine significantly increases the in vivo binding of [(18)F]FESP in the frontal and occipital cortex of drug naive unipolar depressed patients. The increase of the in vivo binding of [(18)F]FESP may reflect a modification in 5HT(2) binding capacity secondary to changes in cortical serotonin activity. (C) 2000 Academic Press.

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.

We propose a renal imaging agent, the 99m Tc complex of the bidentate- N ,S chelate N -(mercaptoacetyl) glycine ( 99m Tc-2GAM), with the imaging characteristics of 99m Tc-DMSA but a faster kidney uptake; chemical evidence supports the formulation of 99m Tc-2GAM as [Tc V (O)(GAM) 2 ] − . After biodistribution and toxicity studies in animals, 99m Tc-2GAM was evaluated in five normal volunteers. 99m Tc-2GAM is rapidly cleared from the blood (t12 = 9 min) and 50% of the ID is excreted in the urine in the first 2 h. Dynamic data show a rapid renal uptake that increases up to 1 h with no significant wash-out between 1 and 8 h. The uptake in each kidney ranges from 11.3% to 20.7% ID. Low, stable liver uptake is observed. No significant activity is detected in other organs. We showed no differences between 99m Tc-2GAM and 99m Tc-DMSA compared in three patients with unilateral kidney disease. We conclude that 99m Tc-2GAM has good practical and dosimetric features for renal imaging.

Objectives. This study sought to investigate whether residual viability of infarcted myocardium may play a role in the pathogenesis of exercise-induced ventricular arrhythmias. Background. We previously showed that transient ischemia within partially infarcted areas often precipitates ventricular arrhythmias during exercise that are consistently obliterated by intravenous nitrates. Methods. We studied 60 patients with chronic stable angina and a previous myocardial infarction, All underwent at least two consecutive exercise stress tests, coronary angiography and stress/rest myocardial perfusion tomography by Tc-99m 2-methoxy isobutyl isonitrile (MIBI). In the last 26 consecutive patients, residual viability was assessed by single-photon emission computed tomography (SPECT) using fluorine (F)-18 fluorodeoxyglucose. Perfusion and metabolic data were evaluated qualitatively by three independent observers in blinded manner, Results. With exercise, 30 patients (group A) consistently developed ventricular arrhythmias (>10 ventricular ectopic beats/min, couplets, nonsustained ventricular tachycardia); the remaining 30 patients (group B) did not, The severity of coronary artery disease (Gensini score) was similar in the two groups. Posterercise SPECT shun ed partial reperfusion of an infarcted area in 28 of 30 patients of group A but in only 9 of 30 of group B (p < 0.0001). Uptake of F-18 fluorodeoxyglucose was observed within the infarcted zone in 10 of 13 and 1 of 13 patients in groups A and B, respectively (p = 0.0003). Conclusions. In patients with myocardial infarction, exercise-induced ventricular arrhythmias appear to be triggered by transient ischemia occurring within a partially necrotic area containing large amounts of viable myocardium. Therefore, occurrence of arrhythmias during exercise may represent a clue to the presence of residual viability within a previously infarcted area. RI Lucignani, Giovanni/C-6773-2008

We compare thallium-201 rest redistribution and fluorine-18 fluorodeoxyglucose ([F-18]FDG) for the assessment of myocardial viability within technetium 99m methoxyisobutylisonitrile (MIBI) perfusion defects in 27 patients with chronic stable coronary artery disease. The following studies were performed: (1) stress Tc-99m-MIBI, (2) rest Tc-99m-MIBI, (3) Tl-201 rest-redistribution single-photon emission tomography, (4) [F-18]FDG positron emission tomography. The left ventricle was devided into II segments on matched tomographic images, The segment with the highest activity at stress was taken as the reference (activity=100%). Perfusion defects at Tc-99m-MIBI rest were classified as severe (activity

Myocardial and whole-body glucose metabolism was assessed in 19 insulin-dependent diabetes mellitus (IDDM) patients. A hyperglycemic clamp was performed 1 ) in the absence of insulin at free fatty acid (FFA) levels of 1.0 mmol/l (test 1); 2 ) in the absence of insulin at low FFA levels (0.1 mmol/l) by means of a lipid-lowering drug, acipimox (test 2); 3 ) during insulin infusion to achieve systemic levels of 400 pmol/l and FFA levels of 0.1 mmol/l (test 3); and 4 ) at the insulin levels of test 3 but increasing FFA to 1.0 mmol/l by means of heparin and intralipid infusion (test 4). Myocardial glucose uptake was measured by positron emission tomography (PET) and 2-[ 18 F]fluoro-2-deoxy-D-glucose. Whole-body glucose uptake was measured in the four conditions by the glucose infusion rate during the PET scanning period. Myocardial glucose uptakes were 40.3 ± 18.0, 395.5 ± 139.6, 852.2 ± 99.1, and 1,388.4 ± 199.1 μmol · kg tissue −1 · min −1 (mean ± SD) and whole-body glucose uptakes were 10.1 ± 2.3, 10.1 ± 3.4, 42.8 ± 5.8, and 30.5 ± 5.6 μmol · kg body wt −1 · min −1 during tests 1, 2, 3, and 4, respectively. Thus, in IDDM patients without coronary artery disease under the condition of hyperglycemia, an increase of myocardial glucose uptake was obtained either by lowering of FFA levels during hypoinsulinemia or by an increase in FFA levels during hyperinsulinemia. In both conditions no significant changes of whole-body glucose uptake were demonstrated.

A method has been developed to match corresponding heart regions from functional echocardiographic (Echo) and metabolic fluorine-18-fluoro-2-deoxy-D-glucose ([18F]FDG) positron emission tomography (PET) studies in individual patients. Echo and PET images are spatially correlated by determining homologous anatomical landmarks (the two papillary muscles and the inferior junction of the right ventricle), identifiable in images obtained by both acquisition modalities. Echo-PET image registration is first performed in the plane identified by the three landmarks, using a rigid rotate-translate scale model. The registration parameters are then used to transform the whole PET volume. This allows a consistent Echo-PET regional analysis, according to a segmental subdivision of the heart. The technique was tested on patients. The overlay of Echo and PET registered images proved the reliability of realignment of the three markers and a good spatial correlation of myocardial walls. This approach to image registration could be applied to other acquisition modalities (such as magnetic resonance imaging and single-photon emission tomography), provided that the three anatomical landmarks are visualized.

We examined 17 angina-free patients with left ventricular dysfunction, referred for surgical decision-making, who presented with no or few signs and symptoms of myocardial ischemia according to treadmill stress test. On cardiac catheterization they were affected by severe multi-vessel coronary artery disease; the mean left end-diastolic pressure of this population was 26.3 +/- 5.5 mm Hg (mean +/- SD) and their mean ejection fraction was 27.6 +/- 4.9% (mean +/- SD). They all were investigated for the presence of viable myocardium by the combined assessment of cardiac perfusion and metabolism using single photon emission tomography with [99mTc] labelled hexakis-2-methoxy-isobutyl-isonitrile [99mTc]MIBI/SPET) and positron emission tomography with [18F]-2-fluoro-2-deoxy-D-glucose ([18F]FDG/PET), respectively. Patients were considered for coronary surgery when [18F]FDG was detectable in at least two cardiac segments with wall motion abnormalities and perfusion defects. Nine patients were operated on, six were medically treated and two were scheduled for heart transplantation. We recorded no in-hospital mortality. At a mean follow-up of 28.4 +/- 9.8 (mean +/- SD) months all surgical patients were alive and their NYHA functional classes have improved, except in one case. Among the patients refused for bypass surgery, three are in stable conditions, three have worsened clinical statuses and two died while waiting for heart transplantation. In conclusion, for patients with bypassable coronaries, left ventricular dysfunction and lack of angina, successful coronary revascularization may be predicted by the presence of viable myocardium demonstrated with positron emission tomography.

Areas of myocardial infarction may retain glycolytic activity and this finding is indicative of tissue viability and predictive of functional recovery after revascularization. In order to assess the relation between the time elapsed from the occurrence of acute myocardial infarction and persistence of myocardial metabolic activity in the infarcted tissue, we prospectively studied 65 patients with previous myocardial infarction diagnosed clinically and by electrocardiographic (Q wave) and enzymatic criteria. All patients underwent coronary angiography and contrast left ventriculography, evaluation of regional myocardial glucose metabolism (in the fasting state) by positron emission tomography (PET) with 2-[18F]fluoro-2-deoxy-D-glucose ([18F]FDG), and assessment of myocardial perfusion by single photon emission computed tomography (SPECT) with technetium-99m methoxyisobutyl isonitrile (99mTc-MIBI). Based on the regional metabolic and perfusion findings, patients were divided into 2 groups, depending on the absence (group 1, 26 patients) or presence (group 2, 39 patients) of [18F]FDG uptake in the underperfused regions. Areas of underperfusion at rest, consistent with the clinically identified myocardial infarction site, were observed in all patients. Severity of coronary artery disease, presence of collaterals, number of hypocontractile segments, and wall motion score did not differ significantly in the 2 groups. The time elapsed from the infarction was significantly greater (1,860 +/- 1,333 days) in group 1 than in group 2 (92 +/- 115 days; p0.0001). Exercise caused an increase in severity and/or extent of resting perfusion abnormalities in a greater proportion of patients of group 1 (53% vs 23%).(ABSTRACT TRUNCATED AT 250 WORDS)

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 arterybypass 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 18-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. Despite the potential limitations due to the semiquantitative analysis of the images, the method appears to provide reliable information for the diagnostic and prognostic evaluation of patients with CAD undergoing CABG and confirms that the identification of hibernating myocardium with 18F-FDG is of paramount importance in the diagnosis of patients undergoing CABG.

To evaluate the usefulness of structural and biochemical imaging techniques for the diagnosis of uveal melanoma, 12 patients with choroidal melanoma were examined. Magnetic resonance imaging was used in 11 of 12 patients, as one had a metal prosthesis. All the subjects underwent single photon planar scintigraphy (SPPS) and single photon emission computed tomography (SPECT) using the 99mTc-labeled F(ab')2 of the anti-melanoma monoclonal antibody 225.28S ([99mTc]MoAb) and positron emission tomography (PET) using [18F]fluorodeoxyglucose ([18F]FDG). Magnetic resonance identified 6 of 11 melanotic lesions (definite melanomas) and 4 of 11 hypomelanotic lesions (probable melanomas), whereas in one case it was inconclusive. [99mTc]MoAb uptake was observed in 5 of 12 lesions using SPPS and 8 of 12 lesions using SPECT. [18F]FDG uptake was observed in 3 of 12 lesions by PET. These results demonstrate that both MR and radioimmunoscintigraphy are sensitive techniques for the diagnosis of choroidal melanomas and suggest that the detection of melanomas by MR, SPPS, and SPECT is largely dependent upon their size. The validity of these conclusions was verified in four subjects in whom the diagnosis was based on MR and/or SPECT findings only and confirmed by histology. The finding that only some of the uveal melanomas of larger size are visualized based on [18F]FDG uptake suggests that melanomas can have either high or low glucose consumption.

The hibernating myocardium refers to resting LV dysfunction due to reduced coronary blood flow that can be partially or completely reversed by myocardial revascularization and/or by reducing myocardial oxygen demand. It is different from the stunned myocardium. Methods for its detection are not yet perfect. Hibernating myocardium has been demonstrated to be present in several clinical subgroups of patients; however, currently its full clinical presence and impact are not adequately defined.

Nuclear medicine and molecular imaging are branches of biomedicine in which biochemical and functional information are displayed in images. However, the interpretation of these images (and thus their significance) depends very much on the ability to quantify the processes being studied and, with the help of detailed morphological imaging, localise them within specific anatomical volumes. Now, thanks to theoretical and empirical advances, both of these problems, for many years conundrums, are in the process of being solved. In the study of coronary artery disease (CAD), the quantification and precise localisation of pathophysiological processes is a growing area of applied clinical research.

Purpose: The aim of this study was to develop a cellular model for the concurrent imaging of reporter genes expression by using positron emission tomography (PET) and bioluminescence imaging (BLI) for the assessment of estrogen receptor activity in vivo in a breast cancer model. Methods: Two reporters were chosen: a mutated form of the dopaminergic D2 receptor (D2R80A) for PET imaging, and the Firefly Luciferase for BLI. The presence of an IRES sequence between the two reporters ensured the coordinated expression driven by the same regulatory sequence containing an estrogen responsive element (ERE). To prevent chromatin effects on reporter expression, the construct was flanked by insulator sequences (Matrix Attachment Region, MAR). Results: In vitro studies showed that the vector was efficient in coordinating the expression of the two genes. Moreover, stably transfected cells implanted in recipient animals maintained their capacity to express the reporters and react to systemic treatments permitting the in vivo study of ERs activity by PET and BLI imaging. In vitro expression analysis after long-term treatments showed different behaviour of the two reporter proteins in monitoring estrogen-dependent transcription outlining the importance of multi-reporter systems. With this model, PET and BLI can be applied to the concurrent evaluation of gene expression induced by estrogen and its analogues by using a bicistronic construct. Conclusion: The combined features of rapid, sensitive, sequential BLI and tomographic and quantitative PET imaging will allow the use of this strategy for the in vivo evaluation of molecular processes also for pharmacodynamic studies.

We evaluated the influence of chronic hypertriglyceridemia and endothelial dysfunction on myocardial glucose uptake (MGU) in Type 2 diabetic patients without coronary heart disease. Patients were divided into two groups according to fasting triglyceride (TG) levels: 5.4 ± 1.1 and 1.5 ± 0.3 mmol/l for high- and normal-TG groups, respectively. Five subjects were assigned to the high-TG group and 11 to the normal-TG group. Age, gender, body mass index, systolic and diastolic blood pressure, glucose, insulin, HbA1c, cholesterol, and HDL cholesterol were similar in the two groups, whereas free fatty acid (FFA) levels were higher in the high-TG group basally and at the end of the clamp. Furthermore, five healthy subjects were subjected to the same protocol and used as the control group. MGU was assessed by using 18F-labeled 2-fluoro-2-deoxy-d-glucose under hyperglycemic-hyperinsulinemic conditions. Basal endothelin-1 and nitric oxide levels were significantly higher in the high-TG group than in the normal-TG and control groups, and cGMP and maximal postischemic vasodilation were significantly decreased in the high-TG group compared with the normal-TG and control groups. However, significant alterations were found in the same parameters in the normal-TG group compared with the control group. By the end of the hyperglycemic clamp, in the high-TG group, MGU was ∼40 and 65% of that in the normal-TG and control groups. MGU negatively correlated with TG, FFA, and endothelin-1, whereas a positive correlation was found with cGMP and maximal postischemic vasodilation. In conclusion, increased TG and FFA levels are risks, in addition to Type 2 diabetes mellitus, for myocardial insulin resistance, endothelial dysfunction, and alteration of nitric oxide/cGMP levels.

Movement disorders, including Parkinson's disease and parkinsonian syndromes, e.g. progressive supranuclear palsy, multiple system atrophy, and Lewy body dementia, may be difficult to differentiate among each other at an early stage, since they may share similar clinical features and response to dopaminergic drugs. As new tracers for imaging the dopamine transporters become available, the use of positron emission tomography (PET) for the differential diagnosis of movement disorders is gaining clinical relevance. Visual interpretation is generally used for PET image analysis. However, the use of some form of less subjective analysis is desirable in order to detect subtle changes that may be difficult to identify by visual interpretation and to achieve an operator independent analysis. To this end this study was aimed at assessing the feasibility of using statistical parametric mapping (SPM) for the clinical evaluation of single PET scans performed with 2-beta-carbomethoxy-3-beta-(4-fluorophenyl)-tropane ( C-beta-CIT-FE). Eleven healthy volunteers and five patients with movement disorders (Parkinson's disease, essential tremor, PSP and Lewy body dementia) were included in this study. Each subject underwent a PET study after i.v. injection of C-beta-CIT-FE. The PET images of C-beta-CIT-FE distribution acquired between 60 and 90 min were spatially fitted into the Talairach and Tournoux space. A template of normal C-beta-CIT-FE distribution was derived from studies in the 11 normal control subjects. Different patterns of reduction of the uptake of the tracer were detected in the basal ganglia of the five patients, in relation to each pathological condition. The patterns of distribution were all consistent with the severity and type of disease. The results of this study demonstrate the feasibility of differentiating among different states of dopaminergic impairment, due to Parkinson's disease and parkinsonian syndromes, by using PET scans with C-beta-CIT-FE and by using the SPM procedure for analysis of the data.

Functional imaging of the presynaptic dopaminergic activity using single-photon emission tomography (SPET) and iodine-123 labelled 2-beta-carboxymethoxy-3-beta-(4-iodophenyl)tropane ([123I]beta-CIT) is important for the assessment of disease severity and progression in patients with Parkinson's disease (PD). However, its capability to discriminate between different extrapyramidal disorders has not yet been assessed. The aim of this study was to evaluate the possibility of differentiating patients with PD and with progressive supranuclear palsy (PSP) by means of this method. The distribution of [123I]beta-CIT in the basal ganglia was assessed in six normal subjects, 13 petients with PD and five patients with PSP in whom the disease was mild. SPET images were obtained 24+/-2 h after i.v. injection of the tracer using a brain-dedicated system (CERASPECT). MR and SPET images were co-registered in four normal subjects and used to define a standard set of 16 circular regions of interest (ROIs) on the slice showing the highest striatal activity. The basal ganglia ROIs corresponded to (1) the head of caudate, (2) a region of transition between the head of caudate and the anterior putamen, (3) the anterior putamen and (4) the posterior putamen. A ratio of specific to non-displaceable striatal uptake was calculated normalising the activity of the basal ganglia ROIs to that of the occipital cortex (V3"). ANOVA revealed a global reduction of V3" in all ROIs of PD and PSP patients compared with normal controls (P

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 differential diagnosis among various types of non-functioning sellar and parasellar tumours is sometimes difficult using currently available methods of morphological imaging. The aim of this study was to define whether assessment of the uptake of [18F]fluoro-ethyl-spiperone (FESP) with positron emission tomography (PET) could be helpful for the differential diagnosis of pituitary adenomas and other parasellar lesions, and for establishing the appropriate therapeutic approach. The population examined comprised 16 patients with the diagnosis of primary tumour of the sellar/parasellar region who were waiting to undergo surgical treatment. The results demonstrated that PET with [18F]FESP is a very specific method for differentiating adenomas from craniopharyngiomas and meningiomas. The visual interpretation of images allows such differentiation at approximately 70 min after tracer injection. Semiquantitative analysis of the dynamic PET data confirmed the results of visual interpretation, demonstrating that the uptake of [18F]FESP was consistently (i.e. throughout the series) at least two- to threefold higher in non-functioning adenomas than in other parasellar tumours as early as 70 min after tracer injection, and that it increased still further thereafter. It is concluded that PET with [18F]FESP might be of clinical value in those cases in which the differential diagnosis among various histological types of sellar tumour is uncertain with conventional methods.

The aims of this study were to assess the sensitivity of positron emission tomography (PET) using [18F]fluorodeoxyglucose (18F-FDG) in the detection of uveal melanoma, and to establish the relationship between pre-operative 18F-FDG uptake and a number of pathological features of uveal melanoma. Twenty consecutive patients with a clinical diagnosis of uveal melanoma were enrolled in the study. 18F-FDG uptake was assessed in all subjects and the following parameters were assessed in 11 enucleated subjects: the mitotic index, the MIB-1 proliferating cell index, number of epithelioid cells, largest tumour diameter, tumoral necrosis and inflammatory infiltration. Tumours with a diameter less than 7.5 mm were not detected by PET, possibly because of limited spatial resolution, and only 7 of 12 tumours with a diameter greater than 7.5 mm were detected. With tumours greater than 7.5 mm in diameter, PET and 18F-FDG allow two subgroups to be distinguished: those with high and those with low glucose consumption. Apart from tumour size, 18F-FDG uptake was not related to the pathological features examined. We hypothesize that 18F-FDG uptake may be related to the ratio of viable to non-viable cells, or to the hypoxic cell fraction within the tumour.

The aim of this study was to evaluate, in 16 patients with drug-resistant partial epilepsy who were waiting to undergo surgical treatment, the relation between positron emission tomography (PET) findings with fluorine-18 fluorodeoxyglucose ([18F]FDG) in the interictal state and the different stereo-electroencephalography (SEEG) patterns that characterize: (a) the epileptogenic zone (low-voltage fast-activity discharge before or concurrent with ictal clinical symptoms), (b) the irritative zone (spikes, spikes and waves, isolated or grouped in short bursts) and (c) the lesional zone (continuous, sometimes polyrhythmic slow waves or continuous delta waves or very important voltage depression). SEEG was performed following an individually defined electrode implantation strategy. Whereas at least one area of hypometabolism was detected by visual interpretation of PET/[18F]FDG images in all the subjects in the study, there was poor agreement between PET/[18F]FDG quantitative measures of regional metabolism and SEEG findings. Normal metabolic rates were found in up to 62% of the areas with abnormal SEEG activity, independent of the type of electrical activity, i.e. epileptogenic, irritative, or lesional, while abnormal metabolic rates were found in up to 23% of the areas with normal SEEG activity. In conclusion, whereas the visual interpretation of interictal studies of glucose utilization in our series of drug-resistant epileptic patients consistently allowed the localization of an area of temporal hypometabolism, the quantitative and regional metabolic analysis demonstrated that such a finding is not specifically related to any of the three very different SEEG patterns (epileptogenic, irritative, lesional) or combinations thereof. These results complement those of previous interictal and ictal single-photon emission tomographic studies and of receptor studies in epileptics, suggesting functional and biochemical heterogeneity within the interictal hypoperfused/hypometabolic area in epileptic patients, and contribute to the debate on the use and interpretation of interictal PET/[18F]FDG studies in patients with medically refractory partial seizures.

Quantitative positron emission tomography (PET) heart studies require the accurate localization of regions of interest (ROIs) on the myocardial wall (MW) and left ventricle (LV). The procedure is often inaccurate, especially when there is low tracer uptake. We implemented a data processing technique to improve the accuracy of the localization of ROIs on the MW and LV in fluorine-18 labelled deoxyglucose ([18F]FDG) PET heart studies. This technique combines transmission data, acquired before tracer administration and used for attenuation correction, and dynamic emission data (DY), acquired to obtain myocardial time-activity curves and used to calculate regional myocardial glucose utilization, to generate a new set of "transmission" images (TRDY) with enhanced contrast between MW and LV. These new transmission images identify the extravascular myocardial tissue and can be used for ROI placement. Validation of the method was performed in 25 patients, studied after an oral glucose load, by drawing irregular ROIs on three transaxial slices outlining the septum and anterior-apical and lateral wall on the last frame of the DY images (steady state) and then on the TRDY images. Two kinds of analysis were performed on a total of 225 myocardial segments: (1) mean counts per pixel in the DY images from ROIs independently drawn on DY and TRDY images were compared; (2) TRDY ROIs were copied onto DY images and repositioned in the event of mismatch between ROIs and myocardial tissue edge. Mean counts per pixel in the DY images from the original and the repositioned TRDY ROIs were compared. An excellent correlation was found in both cases (using TRDY and DY ROIs: y=0.908 x+0.068, r=0.97; using TRDY ROIs alone: y=0.975 x+0.006, r=0.99). This technique can be used for clinical applications in physiological and pathological conditions in which the myocardial [18F]FDG uptake is reduced or minimal, including diabetes and myocardial infarction.

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.

Objectives. We evaluated the sensitivity and specificity of exercise induced ST segment elevation for the detection of residual myocardial viability. Background. Assessment of residual viability after myocardial infarction is relevant for establishing indication for revascularization. We have previously shown that exercise-induced ST segment elevation is a marker of residual viability. Methods. We studied 34 patients,vith a previous Q wave myocardial infarction (anterior in 21, inferior in 13) of whom 18 (group A) had exercise-induced ST segment elevation in more than one lead (mean [+/-SD] 1.8 +/- 0.9 mm, range 1 to 4) and 16 (group B) did not. All patients underwent rest technetium-99m methoxyisobutyl isonitrile single-photon emission computed tomography (SPECT), fluorine-18 (F-18) fluorodeoxyglucose positron emission tomography and coronary angiography. The time elapsed between the infarction and the viability study was 72 +/- 108 days (range 15 to 400) in group A and 516 +/- 545 days (range 14 to 1,800) in group B. Results. The presence and site of previous infarction were confirmed by SPECT studies in all 34 patients. Uptake of F-18 fluorodeoxyglucose within the infarcted area was present in 18 of 18 patients in group A but in only 9 (56%) of 16 in group B (p < 0.01). In patients with an anterior infarction, the sensitivity, specificity and predictive accuracy of exercise-induced ST segment elevation for detection of residual viability were 82%, 100% and 86%, respectively (95% confidence intervals 46% to 83.5%, 59% to 100% and 55.6% to 87.1%, respectively). Conclusions. Exercise-induced ST segment elevation in infarct-related leads has a high specificity and acceptable sensitivity for detection of residual viability within the infarcted area. RI Lucignani, Giovanni/C-6773-2008

Regional cerebral metabolism of glucose (rCMRglu) was evaluated in patients who were in a coma and vegetative state to determine the level of brain function during these conditions. rCMRglu was measured in 17 discrete brain regions with (/-) [18F] -fluoro-2-deoxy-D-glucose (FDG) and positrn emission tomography (PET) in 15 patients with ;brain pathology subsequent to cardiorespiratory arrest (CA), head trauma (HT), or brain ischemia (BI) resulting from cerebrovascular accident or brain surgery. Five comatose patients (Coma group, n = 5), and 10 vegetative state patients (VS, patients awake but not aware) were studied. The VA patients were subdivided, according to the length of their VS condition, into a VS group (n = 6, < 3 months if CA or BI patients, or < 12 months if HT patients) and a persistent vegetative state group (PVS, n = 4, > 3 months if CA or BI patients of > 12 months if HT patients.) Ten normal age-matched subjects served as control. Global CMRglu was 6.72 +/- 0.93 (+/-SD) mg/100 g/min in control subjects. It was significantly (p < - 0.001) reduced to 3.70 +/- 61 in coma, to 3.45 +/- in VS, and to 2.33 +/- 0.34 mg/100 g/min in PVS patients. rCMRglu was significantly reduced (p < - 01001) from control values in all the 17 structures surveyed in every patient. In the Coma and VS groups, there was an overlapping of rCMRglu in the majority of the brain structures. (ABSTRACT TRUNCATED AT 250 WORDS)

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)

The imaging of cerebral gliomas with radiolabelled monoclonal antibodies (MoAbs) has been previously reported. However, previous studies have been hampered by the drawback of a low tumour to non-tumour ratio. In order to overcome this problem we have developed a three-step pre-targeting method using the avidin-biotin system. The rationale of this technique consists in vivo labelling of biotinylated MoAbs targeted onto tumour deposits, when most of the unbound antibodies have been cleared from the bloodstream as avidin-bound complexes. The anti-tenascin MoAb BC2, specific for the majority of gliomas, was biotinylated and 1 mg was administered i.v. in 20 patients with histologically documented cerebral lesions. After 24–36 h, 5 mg avidin was injected i.v. followed 24 h later by a third i.v. injection of 0.2 mg PnAO-biotin labelled with 15–20 tnCi technetium-99m. No evidence of toxicity was observed. Whole-body biodistribution was measured at 20 min, 3 h and 5 h post-injection. [99mTc]PnAO-bio-tin had a fast blood clearance and was primarily excreted through the biliary system. A dedicated single-photon emission tomography system was used to acquire brain tomographic images 1–2 h after the administration of [99mTc]PnAO-biotin. Tumours were detected in 15/18 glioma patients with a tumour to non-tumour ratio of up 14:1. This three-step method, based on the sequential administration of anti-tenascin MoAb BC2, avidin and [99mTc]PnAO-biotin, can support computed tomography or magnetic resonance imaging for the diagnosis and follow-up of patients with glioma. Further studies are required to evaluate the potential of this technique for therapeutic application.

The effects of tissue heterogeneity on the estimation of regional cerebral glucose utilization (rCMRglc) in normal humans with [18F]2-fluoro-2-deoxy-d-glucose ([18F]FDG) and positron emission tomography (PET) were compared with respect to the various kinetic models of the [18F]FDG method. The kinetic models were conventional homogeneous tissue models of the [18F]FDG method, with (4K Model) and without (3K Model) a rate constant to account for an apparent loss of [18F]2-fluoro-2-deoxy-d-glucose-6-phosphate ([18F]FDG-6-P), and a tissue heterogeneity model (TH Model). When either of the kinetic models designed for homogeneous tissues was applied to heterogeneous tissues, estimates of the rate constant for efflux of [18F]FDG from the tissue ( k*2) and of the rate constant for phosphorylation of [18F]FDG ( k*3) decreased as the duration of the experimental period was increased. When the 4K Model was used, estimates of the rate constant for the apparent dephosphorylation of [18F]FDG-6-P ( k*4) were significantly greater than zero and fell with increasing duration of the experimental period. Although the TH Model included no term to describe an apparent dephosphorylation of [18F]FDG-6-P, the fit of the TH Model to the time course of total tissue radioactivity was at least as good as and often better than the fit of the 4K Model in the 120-min period following the pulse of [18F]FDG. Hence, the high estimates of k*4 found in PET studies of ≤120 min can be explained as the consequence of measuring radioactivity in a heterogeneous tissue and applying a model designed for a homogeneous tissue; there remains no evidence of significant dephosphorylation of [18F]FDG-6-P in this time period. Furthermore, use of the 4K Model led to an overestimation of rCMRglc; whole-brain glucose utilization calculated with the 4K Model was >20% higher than values usually obtained in normal humans by the model-independent Kety–Schmidt technique. rCMRglc was accurately estimated by the TH Model and, in experimental periods sufficiently long to minimize the effects of tissue heterogeneity, also by the original 3K Model of the deoxyglucose method.

Positron emission tomography (PET) is a technique in nuclear medicine that allows the in vivo assessment of the pattern of distribution and rates of biochemical processes. We report the use of PET to obtain an in vivo metabolic picture of a choroidal melanoma. Report of a Case. —A 67-year-old white man was referred to our hospital because of a 6-month history of blurred vision in the left eye. The ophthalmoscopic examination demonstrated a pigmented mass in the inferotemporal quadrant. Slit-lamp biomicroscopy with contact lens, ultrasonography, fluorescein angiography, magnetic resonance imaging of the orbit, and single-photon emission tomography immunoscintigraphy with antimelanoma monoclonal antibodies were all consistent with the diagnosis of malignant melanoma. No systemic metastases were detected. The contralateral eye was normal. After informed consent had been obtained from the patient, a PET study was performed using the ECAT 931/04-12 tomograph (CTI/Siemens Gammasonic, Des Plaines, Ill) 40 minutes after the intravenous

The metabolic degradation and the kinetics of the cerebral uptake of N, N, N'-trimethyl- N'-(2-hydroxy-3-methyl- 5-[125I]iodobenzyl)-1, 3-propanediamine ([125I]HIPDM) have been studied in conscious, adult male Sprague-Dawley rats to determine its suitability as a tracer for the quantitative measurement of regional CBF (rCBF). rCBF was calculated by the indicator fractionation and the tissue equilibration methods in experiments of different durations up to 1 h. The values of rCBF obtained with [125I]HIPDM were compared with those obtained in concurrent measurements with [14C]iodoantipyrine in the same animals. Results of the experiments demonstrate that [125I]HIPDM is an inadequate tracer for use with the indicator fractionation method and that any method that employs [125I]HIPDM for the determination of rCBF must take into account its metabolic degradation, diffusion limitations, and bidirectional flux across the blood-brain barrier. With the tissue equilibration method, consistent determinations of rCBF may be possible with [125I]HIPDM by measurement of the time course of its concentration in arterial blood, corrected for the presence of 125I-labeled metabolic products, and its concentration in the brain at any time up to 1 h after its administration. The method may be adapted to measure rCBF in humans by means of single-photon emission tomography with [123I]HIPDM.

The assessment of neurochemical processes in vivo has received much attention in the past decade as techniques such as positron or single photon emission tomography (PET and SPET), and magnetic resonance spectroscopy (MRS) have become more available. With PET and SPET, basic processes, such as blood flow and oxygen or glucose metabolism, can be regionally assessed, along with more specific functions such as the production, release, and reuptake of neurotransmitters and their occupancy of specific receptors. At the same time, MRS can reveal changes in concentration of several hydrogenate compounds in the brain. All these methods have been extensively applied for research in neurology, and some applications have reached the clinical level, namely for the study of degenerative diseases, motor-neuron diseases, movement disorders, cerebrovascular diseases, and epilepsy. This article focuses on the most relevant information that can be obtained with these complementary techniques to help clinicians in the assessment of neurological diseases.

We assessed the relative usefulness of whole-body planar scintigraphy with 99Tcm-methoxyisobutyl isonitrile (99Tcm-MIBI), 2-[18F]fluoro-2-deoxy-D-glucose (18F-FDG-RS) rectilinear scanning and with diagnostic and therapeutic doses of 131I, for the detection of local recurrences and metastatic lesions in 12 patients with thyroid carcinoma and elevated thyroglobulin serum levels. All images were evaluated independently by three experienced observers to define the number and location of metastatic lesions. 18F-FDG-RS and 99Tcm-MIBI scintigraphy provided similar results, but the tracer that allowed the detection of the highest number of metastases was 99Tcm-MIBI. Both 99Tcm-MIBI scintigraphy and 18F-FDG-RS appear to be more sensitive than 131I scintigraphy for the detection of metastases of thyroid carcinoma. Tomographic acquisitions were also performed on a limited field of view in each subject and, as expected, 18F-FDG-PET was more sensitive than 18F-FDG-RS. 99Tcm-MIBI scintigraphy, a widely available and relatively non-expensive technique, therefore sems suitable for the assessment and follow-up of patients with metastatic thyroid carcinoma and does not require the withdrawal of hormone therapy for lesion imaging.