A. Del Sole

Effects of fluvoxamine treatment on the in vivo binding of [F-18]FESP in drug naive depressed patients: a PET study

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 fluoro-ethyl-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.

Increased interictal cerebral glucose metabolism in a cortical-subcortical network in drug naive patients with cryptogenic temporal lobe epilepsy.

Positron emission tomography with [18F]-2-fluoro-2-deoxy-D-glucose ([18F]FDG) has been used to assess the pattern of cerebral metabolism in different types of epilepsies. However, PET with [18F]FDG has never been used to evaluate drug naive patients with cryptogenic temporal lobe epilepsy, in whom the mechanism of origin and diffusion of the epileptic discharge may differ from that underlying other epilepsies. In a group of patients with cryptogenic temporal lobe epilepsy, never treated with antiepileptic drugs, evidence has been found of significant interictal glucose hypermetabolism in a bilateral neural network including the temporal lobes, thalami, basal ganglia, and cingular cortices. The metabolism in these areas and frontal lateral cortex enables the correct classification of all patients with temporal lobe epilepsy and controls by discriminant function analysis. Other cortical areas--namely, frontal basal and lateral, temporal mesial, and cerebellar cortices--had bilateral increases of glucose metabolism ranging from 10 to 15% of normal controls, although lacking stringent statistical significance. This metabolic pattern could represent a pathophysiological state of hyperactivity predisposing to epileptic discharge generation or diffusion, or else a network of inhibitory circuits activated to prevent the diffusion of the epileptic discharge.

Assessment of radiological vertebral fractures in HIV‐infected patients: clinical implications and predictive factors

The aim of this study was to evaluate the clinical impact of including lateral spine X‐ray in the screening of bone diseases in HIV‐positive patients.

The prognostic value of baseline 18 F-FDG PET/CT in steroid-naïve large-vessel vasculitis: introduction of volume-based parameters

PurposeThe aim of this study was to analyse if the result of a baseline 18F-fluorodeoxyglucose (FDG) positron emission tomography (PET)/CT scan, in large-vessel vasculitis (LVV) patients, is able to predict the course of the disease, not only in terms of presence/absence of final complications but also in terms of favourable/complicated progress (response to steroid therapy, time to steroid suspension, relapses, etc.).MethodsA total of 46 consecutive patients, who underwent 18F-FDG PET/CT between May 2010 and March 2013 for fever of unknown origin (FUO) or suspected vasculitis (before starting corticosteroid therapy), were enrolled. The diagnosis of LVV was confirmed in 17 patients. Considering follow-up results, positive LVV patients were divided into two groups, one characterized by favourable (nine) and the other by complicated progress (eight), on the basis of presence/absence of vascular complications, presence/absence of at least another positive PET/CT during follow-up and impossibility to comply with the tapering schedule of the steroid due to biochemical/symptomatic relapse. Vessel uptake in subjects of the two groups was compared in terms of intensity and extension. To evaluate the extent of active disease, we introduced two volume-based parameters: “volume of increased uptake” (VIU) and “total lesion glycolysis” (TLG). The threshold used to calculate VIU on vessel walls was obtained by the “vessel to liver” ratio by means of receiver-operating characteristic analysis and was set at 0.92 × liver maximum standardized uptake value in each patient.ResultsMeasures of tracer uptake intensity were significantly higher in patients with complicated progress compared to those with a favourable one (p < 0.05). Measures of disease extension were even more significant and TLG emerged as the best parameter to separate the two groups of patients (p = 0.01).ConclusionThis pilot study shows that, in LVV patients, the combined evaluation of the intensity and the extension of FDG vessel uptake at diagnosis can predict the clinical course of the disease, separating patients with favourable or complicated progress.

Diagnostic performance of PET/CT with tracers other than F-18-FDG in oncology : an evidence-based review

Fluorine-18-fluorodeoxyglucose (F-18-FDG) is the most used positron emitter radiopharmaceutical worldwide. This glucose analogue allows to study the glucose metabolism which is often increased in many tumors. Nowadays the diagnostic performance of positron emission tomography/computed tomography (PET/CT) using F-18-FDG in different tumors is well known. On the other hand, to date, there is an increasing interest for the use of PET tracers other than F-18-FDG in oncology, because they allow to study different metabolic pathways or receptor expression. The aim of this review is to summarize the scientific literature about the diagnostic performance of PET/CT using tracers other than F-18-FDG in oncology through an evidence-based approach. In particular, the results of meta-analyses (representing the highest level of evidence) on the diagnostic performance of PET tracers other than F-18-FDG in different tumors are described. Furthermore, recommendations for the use of different PET tracers in oncology are provided based on existing literature data.

Myocardial perfusion scintigraphy dosimetry: optimal use of SPECT and SPECT/CT technologies in stress-first imaging protocol

PurposeOver the past decade, nuclear medicine experts have been seeking to minimize patient exposure to radiation in myocardial perfusion scintigraphy (MPS). This review describes the latest technological innovations in MPS, particularly with regard to dose reduction.MethodsWe searched in PubMed for original clinical papers in English, published after 2008, using the following research criteria: (dose) and ((reduction) or (reducing)) and ((myocardial) or (cardiac) or (heart)) and ((nuclear medicine) or (nuclear imaging) or (radionuclide) or (scintigraphy) or (SPET) or (SPECT)). Thereafter, recent reviews on the topic were considered and other relevant clinical papers were added to the results.ResultsOf 202 non-duplicate articles, 17 were included. To these, another eight papers cited in recent reviews were added. By optimizing the features of software, i.e., through algorithms for iterative reconstruction with resolution recovery (IRRs), and hardware, i.e., scanners and collimators, and by preferring, unless otherwise indicated, the use of stress-first imaging protocols, it has become possible to reduce the effective dose by at least 50% in stress/rest protocols, and by up to 89% in patients undergoing a diagnostic stress-only study with new technology. With today’s SPECT/CT systems, the use of a stress-first protocol can conveniently be performed, resulting in an overall dose reduction of about 35% if two-thirds of stress-first examinations were considered definitively normal.ConclusionUsing innovative gamma cameras, collimators and software, as well as, unless otherwise indicated, stress-first imaging protocols, it has become possible to reduce significantly the effective dose in a high percentage of patients, even when X-ray CT scanning is performed for attenuation correction.

Acute effect of 3-(4-acetamido)-butyrril-lorazepam (DDS2700) on brain function assessed by PET at rest and during attentive tasks

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 [18F]fluoro-deoxy-D-glucose ([18F]FDG) under baseline conditions and following the administration of DDS2700. Regional cerebral blood flow (rCBF) was measured by PET and 15O-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 [18F]FDG and water may provide complementary information in pharmacodynamic studies.

Dementia with Lewy bodies with supranuclear gaze palsy: a matter of diagnosis

Description of a case of probable dementia with Lewy bodies featuring parkinsonism, dementia and supranuclear gaze palsy. This is the first patient to our knowledge affected with vertical gaze palsy receiving clinical diagnosis of DLB when alive and to be treated with cholinesterase inhibitors.

Relation between myocardial 18F-FDG uptake in the fasting state and coronary angiography in patients with coronary artery disease

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: 10–50%, 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. Although the 18F-FDG index is inadequate for estimating the severity of CAS, it provides useful information on the metabolism of segments perfused by collateral circulation.

Effective and equivalent dose minimization for personnel in PET procedures: how far are we from the goal?

Radiation dose limitation in patients undergoing nuclear medicine procedures is accomplished through adherence to the principles of justification and optimization, while radiation doses to operators are controlled mainly by reducing exposure times, using shielding, and increasing the distance from the source. In both cases, however, a key role in dosemanagement can also be played by innovative technologies, making this an important issue not only for nuclear medicine specialists, medical physicists, and technologists, but also for biomedical engineers and for industry [1–3]. Whereas the quest to achieve effective dose optimization for patients, in accordance with the ALARA principle, is currently the focus of intensive research and technological development activity, the need to develop and implement new devices to reduce operator exposure to ionizing radiation seems to be a secondary concern. Twenty years ago, for the concerns raised by the radiation energy of the highly penetrating 511 keV annihilation photons, the first study of personnel dosimetry in positron emission tomography (PET) found that the effective radiation doses to technologists in PET centres (mostly carrying out F-FDG studies) were within recommended occupational radiation protection guidelines [4], and since then, comparatively little attention has been paid to the problem of operator exposure. However, in view of the now constantly increasing number of PET procedures being carried out in centres around the world, the use of positron emitters is becoming a real and a growing occupational concern. In this regard, it needs to be appreciated, in particular by those working in nuclear medicine on a day to day basis, that PET requires different radiation protection strategies from those usually adopted in general nuclear medicine, for reducing both the effective and equivalent dose to the extremities below the acceptable levels. Despite the use of routine precautionary measures, including the use of dedicated hot-cells, occupational doses in PET are higher than they need to be in order to obtain good quality examinations. The physical properties of positron emitting radiopharmaceuticals and the optimization of patient doses are both factors that, in addition to the greater number of PET studies now performed, can result in unnecessarily high occupational doses if adequate radiation protection operational procedures for working with positron emitting radionuclides are not envisaged, explained and rigorously adopted across all PET units, in accordance with local conditions. There are in fact three sources of exposure that contribute to the total personnel exposure for a given PET study, keeping in mind that their burden can be shared among different operators: indeed, exposure occurs during i) the patient undergoing the procedure, ii) the vial during the dispensing of the radiopharmaceutical, and iii) the syringe during the injection of the radiopharmaceutical. 1 The decay of positron emitters produces four times the amount of energy in photons than the decay of technetium-99 m does. The gamma ray constant of 511 keV annihilation photons is 1.81 μSv/h per MBq at 30 cm from an unshielded point source, while that of 140 keV photons is 0.26 μSv/h per MBq at 30 cm from an unshielded point source. Whereas the half-value layer (HVL) of 140 keV photons consists of approximately 0.03 cm of lead, 4.5 cm of water and 4000 cm of air, the HVL of 511 keV photons comprises approximately 0.6 cm of lead, 7.5 cm of water, and 6500 cm of air. For the sake of comparison, the dose rate due to a given technetium-99 m activity corresponds to 14 % of that delivered by the same amount of fluorine-18 activity.