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Biomedical subjects

G Lucignani

Publications and source records attributed to G Lucignani.

At least 19 recordsLinked to original sources
PubMed2006

The dynamics of estrogen receptor activity.

In the latest few years, the merging of imaging and animal engineering technologies has led to the generation of innovative tools that provide the opportunity to look into the dynamics of specific molecular events in living animals during their entire life under a completely renewed perspective. These tools will have a profound impact not only on basic research, but also on drug discovery and development allowing to depict the activity of any therapeutic agents in all their designed targets as well as in the organs where they may cause undesired effects. Along this research line, our laboratory has recently described the first animal model reporting the state of activity of estrogen receptors (ERs) in real time: the ERE-luc reporter mouse. The application of optical imaging to the ERE-luc has allowed an unprecedented in depth view of estrogen signaling in all of its target tissues. For example, the analysis of the state of activity of ERs in the physiological setting of the estrous cycle has provided compelling evidence that hormone-independent mechanisms are responsible for activating ERs in non-reproductive organs. This discovery may pave the way to a rational basis for the development of novel, more selective and effective treatments for menopause.

Animals↗
PubMed2006

Molecular imaging: a new way to study molecular processes in vivo.

Non-invasive imaging of reporter gene expression using different imaging modalities is increasing its role for the in vivo assessment of molecular processes. Multimodality imaging protocols overcome limitations to a single imaging modality and provide a thorough view of specific processes, often allowing a quantitative measurement and direct visualization of the process in a specific target organ or tissue. The use of the right reporter gene for the development of animal models and the characterization of its expression in different conditions and tissues is fundamental for basic, translational and future pharmacological applications of a given model. This paper summarizes the major steps in the development and evaluation of a specific animal model for in vivo molecular imaging studies and describes the first example of an animal model designed for the in vivo assessment of a specific receptor activity and its possible evolution towards multimodality imaging analysis.

Animals↗
PubMed2005

Why does the agonist [(18)F]FP-TZTP bind preferentially to the M(2) muscarinic receptor?

PURPOSE: Preferential binding of FP-TZTP at the M(2) receptor in vivo led to investigation of [(18)F]FP-TZTP as a potential PET tracer for Alzheimer's disease, in which a substantial reduction of M(2) receptors has been observed in autopsy studies. We hereby investigated in vitro the FP-TZTP behavior to further elucidate the properties of FP-TZTP that lead to its M(2) selectivity. METHODS: Chinese hamster ovarian cells expressing the five subtypes of human muscarinic receptor as well as the wild type were harvested in culture to assess equilibrium binding. Specific binding was calculated by subtraction of non-specific binding from total binding. Internal specific binding was calculated by subtraction of external specific binding from the total specific binding. Saturation assays were also performed to calculate B(max), K(i), and IC(50). In addition, equilibrium binding and dissociation kinetic studies were performed on rat brain tissue. Selected regions of interest were drawn on the digital autoradiograms and [(18)F]FP-TZTP off-rates were determined by measurement of the rate of release into a buffer solution of [(18)F]FP-TZTP from slide-bound cells that had been preincubated with [(18)F]FP-TZTP. RESULTS: At equilibrium in vitro, M(2) subtype selectivity of [(18)F]FP-TZTP was not evident. We demonstrated that ATP-dependent mechanisms are not responsible for FP-TZTP M(2) selectivity. In vitro off-rate studies from rat brain tissue showed that the off-rate of FP-TZTP varied with the percentage of M(2) subtype in the tissue region. CONCLUSION: The slower dissociation kinetics of FP-TZTP from M(2) receptors compared with the four other muscarinic receptor subtypes may be a factor in its M(2) selectivity.

Animals↗
PubMed2005

Assessing cell trafficking by noninvasive imaging techniques: applications in experimental tumor immunology.

Tracer methods are increasingly being exploited to examine the trafficking patterns of cells transferred into recipient models of diseases, to optimize immune cell therapies, and to assess cancer gene therapy and vaccines in various cancer models. In animal cancer models, noninvasive monitoring by imaging tumor response could significantly facilitate the development of immune cell therapies against cancer. Currently, ex vivo lymphocyte labeling is primarily done by direct labeling. Major advances in cell labeling procedures have led to the use of reporter constructs to assess gene expression in vivo. With this novel technique, the reporter gene marks the cell with a specific protein that distinguishes the cell and its cellular progeny from other cells after migration, homing and mitosis. Several in vivo imaging procedures, including positron emission tomography, single photon emission tomography and magnetic resonance imaging, have been rescaled for studies in small animals. Other methods initially used for in vitro bioluminescence and fluorescence studies have also been refined for in vivo studies. When combined, these methods allow to assess cell trafficking in a noninvasive fashion, beyond lymphocyte response to inflammation, including metastatic diffusion and stem cell transplantation.

Animals↗
PubMed2004

The use of standardized uptake values for assessing FDG uptake with PET in oncology: a clinical perspective.

Among clinicians who use positron emission tomography (PET), the standardized uptake value (SUV) is a popular semi-quantitative value that can be easily assessed whenever a PET study is performed under physiological and pathological conditions. It provides an index of regional tracer uptake normalized to the administered dose of tracer. The simplicity of SUV assessment contrasts with the complexity of full quantitative procedures requiring blood sampling and possibly dynamic scanning, which limits patient throughput and significantly increases the workload of a PET centre. Two main clinical conditions/variables affect the significance and usefulness of the SUV: the type and stage of the disease being assessed. Diagnosis, prognosis and therapy monitoring represent the possible uses of SUV. In the above clinical conditions an SUV may provide information about the single lesion in which it is assessed, but the utility of such information depends largely on its integration with all the available clinical and instrumental data.

Algorithms↗
PubMed2004

Economic analyses on the use of positron emission tomography for the work-up of solitary pulmonary nodules and for staging patients with non-small-cell-lung-cancer in Italy.

AIM: Increasing ageing of the population and tumor incidence, along with worldwide rationing of the resources for public health systems, spur the use of economic analyses for the choice of strategies and technologies in the assessment and management of cancer patients. Incidence and clinical managing of tumors vary in different countries even if positron emission tomography (PET) with 2-deoxy-2-[18F]-fluoro-D-glucose (FDG) is becoming a routine clinical method for diagnosis, staging, treatment monitoring and follow-up in a variety of tumors. Available data indicate that PET can be considered a superior alternative or complementary tool to other well-established methods. However, in spite of the above and of the rapidly increasing number of PET centers in Europe, USA and Japan, only a few studies have dealt with some of the economic aspects raised by the clinical use of PET because of differences in values of reimbursements and health costs. The main aim of this study is to propose and discuss an economic model of analysis for PET applications in the field of detection and management of pulmonary tumors. METHODS: In this study 2 assessments were performed by decision tree analysis on the economic impact of the availability of PET on decision-making processes for 2 conditions: solitary pulmonary nodules assessment and non-small-cell lung cancer (NSCLC) staging. In order to define a methodology consistent with the system of reimbursement and the prevalent clinical views of the Italian National Health Service, data on costs, death probability, and life expectancy were gathered from the literature and from the Italian system of reimbursement (ROD-DRGs). RESULTS: The results of the cost minimization analysis demonstrate that the use of PET in the diagnostic path for the workup of patients with SPN reduces the overall diagnostic costs, by approximately 50 Euro per patient, by reducing inappropriate invasive diagnostic investigation and their complications. The results of the cost effectiveness analysis demonstrate that the use of PET in the diagnostic path for the staging of patients with NSCLC reduces the overall diagnostic costs by approximately 108 Euro for added year, by reducing inappropriate surgical interventions and their complications. CONCLUSION: Both analyses are based on standard methods used in the literature, so our conclusions can be compared with results and assessments of similar studies in different countries and health care systems. Also in the Italian case, the use of an economic assessment provides relevant information on the efficacy and effectiveness of PET.

Carcinoma, Non-Small-Cell Lung↗
PubMed2004

Position of nuclear medicine techniques in the diagnostic work-up of brain tumors.

Although any patient with a suspected brain tumor, either primary or metastatic, should be studied with anatomic imaging modalities such as angiography, computerized tomagraphy (CT) or magnetic resonance imaging (MRI), nuclear medicine techniques are available to further characterize some biological features of brain lesions and help in diagnosis and therapy planning. Bloob-brain-barrier disruption can be easily assessed with single-photon emission tomography (SPET), whereas focal metabolic changes can be better demonstrated by positron emission tomography (PET) as specific radiopharmaceuticals are available to detect changes in glucose utilization and aminoacid uptake with this technique. Expression of specific tumoral antigens is the basis of imaging with radioimmunoscintigraphy, a promising technique that can be applied to brain tumor therapy. The major clinical applications of nuclear medicine in the study of brain tumors -- evaluation of the extension of a tumoral mass, differential diagnosis and evaluation of therapy and prognosis -- are discussed.

Brain Neoplasms↗
PubMed2004

Comparative evaluation of two methods to assay thyroglobulin serum concentrations in patients with differentiated thyroid carcinomas.

AIM: This study was aimed at the comparative assessment of the analytical and clinical performances of 2 tests for thyroglobulin (Tg) assays: the Dynotest Tg-Plus immunoradiometric assay (IRMA), a new method that might be of interest for its claimed superior sensitivity compared to other methods, and the HTGK-2 IRMA, one of the test currently used in clinical routine. METHODS: The study was performed in serum samples from 157 patients with differentiated thyroid carcinoma (DTC). The clinical sensitivity of the test was evaluated in patients with and without thyroid stimulating hormone (TSH) suppression. RESULTS: The lowest detectable Tg concentration values and the within-assay coefficient of variation (CV) were 0.4 and 0.8 microg/L and 5% and 3% for the Dynotest Tg-Plus assay and the HTGK-2 assay, respectively; the between-assay CV was 6% for both assays. The clinical results of the Dynotest Tg-Plus and those of the HTGK-2 kit were similar in both DTC patient populations, either under or off the TSH suppressive treatment. In spite of the manufacturer's statement that the calibrators of both assays had been standardized against the same common reference (standard CRM 457 of the Community Bureau of References), the Dynotest Tg-Plus test underrated by a factor of 0.5 the Tg values measured by means of HTGK-2 IRMA. CONCLUSION: The sensitivity of the Dynotest Tg-Plus IRMA appears to be similar to that of the HTGK-2 assay.

Adolescent↗
PubMed2002

The feasibility of statistical parametric mapping for the analysis of positron emission tomography studies using 11C-2-beta-carbomethoxy-3-beta-(4-fluorophenyl)-tropane in patients with movement disorders.

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.

Adult↗
PubMed2001

Anatomical and biochemical investigation of primary brain tumours.

Cancerous transformation entails major biochemical changes including modifications of the energy metabolism of the cell, e.g. utilisation of glucose and other substrates, protein synthesis, and expression of receptors and antigens. Tumour growth also leads to heterogeneity in blood flow owing to focal necrosis, angiogenesis and metabolic demands, as well as disruption of transport mechanisms of substrates across cell membranes and other physiological boundaries such as the blood-brain barrier. All these biochemical, histological and anatomical changes can be assessed with emission tomography, X-ray computed tomography (CT), magnetic resonance imaging (MRI) and magnetic resonance spectroscopy (MRS). Whereas anatomical imaging is aimed at the diagnosis of brain tumours, biochemical imaging is better suited for tissue characterisation. The identification of a tumoural mass and the assessment of its size and vascularisation are best achieved with X-ray CT and MRI, while biochemical imaging can provide additional information that is crucial for tumour classification, differential diagnosis and follow-up. As the assessment of variables such as water content, appearance of cystic lesions and location of the tumour are largely irrelevant for tissue characterisation, a number of probes have been employed for the assessment of the biochemical features of tumours. Since biochemical changes may be related to the growth rate of cancer cells, they can be thought of as markers of tumour cell proliferation. Biochemical imaging with radionuclides of processes that occur at a cellular level provides information that complements findings obtained by anatomical imaging aimed at depicting structural, vascular and histological changes. This review focusses on the clinical application of anatomical brain imaging and biochemical assessment with positron emission tomography, single-photon emission tomography and MRS in the diagnosis of primary brain tumours, as well as in follow-up.

Brain↗
PubMed2001

PET in psychopharmacology.

Emission tomography techniques and, in particular, positron emission tomography (PET) enable the in vivo study of several physiological and neurochemical variables in human subjects using methods originally developed for quantitative autoradiography. In particular, PET allows one to evaluate in human subjects: (a) the effect of specific neurochemical challenges on regional brain function at rest or under activation; (b) the activity of neurotransmitters and the regional expression of specific molecular targets during pathology including their modulation by drug treatment; (c) the kinetics of drug disposition and activity directly in the target organ. This is of primary interest in the field of biological psychiatry and in psychoactive drugs development, where it is particularly difficult to reproduce human diseases using animal models in view of the peculiarity of this field and the large heterogeneity of each psychiatric illness also inside the same clinical definition. The aim of this paper is to review the principal strategies and the main results of the use of PET in psychopharmacology.

Animals↗
PubMed2001

Cardiovascular outcomes after kidney-pancreas and kidney-alone transplantation.

BACKGROUND: This study retrospectively assessed, with an intention-to-treat analysis, the effect of kidney-pancreas transplantation (KP) on survival and cardiovascular outcome in type 1 diabetic uremic patients. METHODS: A total of 351 uremic type 1 diabetic patients were enrolled on a waiting list for KP: 130 underwent KP transplantation, 25 underwent kidney transplantation alone (KA), whereas 196 patients remained on dialysis (WL). The three populations had similar cardiovascular conditions. Actuarial survival rates and causes of death were recorded over a period of seven years. Finally, 23 KP and 13 KA patients underwent left radionuclide ventriculography, during a follow-up of four years. RESULTS: In the entire group of 351 patients the seven-year survival rate was 77.4% for KP, 56.0% for KA and 39.6% for WL (KP vs. WL, P = 0.01). Cardiovascular death rate was 7.6% in KP, 20.0% in KA and 16.1% in WL (KP versus WL, P = 0.03; KP vs. KA, P = 0.16). In the subsample studied with radionuclide ventriculography, left ventricular ejection fraction improved in KP, but did not in KA, with significant differences between groups at two and four years. At four years only the KP patients presented normal values of diastolic parameters, including the peak filling rate, time-to-peak filling rate, and peak filling rate/peak ejection rate ratio. Glycated hemoglobin was negatively associated with the ejection fraction, peak filling rate and peak filling rate/peak ejection rate ratio, and positively associated with the time-to-peak filling rate. CONCLUSIONS: Normalization of blood glucose metabolism and improvement of blood pressure control obtained with KP transplant is associated with positive effects on survival, cardiovascular death rate, and left ventricular function.

Adult↗
PubMed2001

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-gamma-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.

Adult↗
PubMed2000

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.

Adult↗