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M Chianelli

Publications and source records attributed to M Chianelli.

At least 19 recordsLinked to original sources
PubMed2006

New radiopharmaceuticals for imaging rheumatoid arthritis.

Rheumatoid arthritis (RA) is an incapacitating chronic inflammatory disease of the joints that, because of frequent relapses, requires life-long treatment. In patients affected with RA an important treatment objective is to achieve specific immune suppression in order to extinguish the immune process and arrest the disease, thus preventing or delaying complications and avoiding disease recurrence. The side effects of anti-inflammatory drugs given to improve the quality of life of these patients can be reduced with the use of specific immune therapies that block, as selectively as possible, the pathologic mechanism responsible for the disease. New therapeutic options for specific, targeted therapies for treating RA are being developed, and trials to assess the efficacy and safety of these approaches are underway. However, these therapies rely primarily on clinical assessment to evaluate treatment efficacy. It would be useful, therefore, to have an objective and reliable method that directly highlights the immune processes underlying the disease. Currently available radiopharmaceuticals for imaging RA, with a special emphasis on recently developed agents and their use in therapy decision-making and follow-up are the focus of this article.

Arthritis, Rheumatoid↗
PubMed2006

Receptor targeting agents for imaging inflammation/infection: where are we now?

Over the past 20 years, radiopharmaceutical research has brought to market a wide variety of drugs that aid in the management of infection and inflammation. Finding the best clinical application for existing radiopharmaceuticals can be a challenging task, as clinicians now have to choose from an array of many different radiopharmaceuticals, each suited to identify a specific type of inflammation. With this review, we describe the features of receptor-targeting agents and present the main advantages and limitations to their application in the diagnosis of inflammation and infection. The receptor-specific agents described here include peptides and antibodies as well as radiolabeled antibodies employed for the specific targeting of neutrophils, bacteria, lymphocytes, and molecules involved in inflammatory processes. Because these agents bind to specific receptors, they allow the mapping of receptor expression in vivo. Such mapping represents the future of nuclear medicine imaging, as it aids in diagnosing the type of inflammation, in therapy decision-making, in selecting suitable candidates for therapy, and in evaluating treatment efficacy.

Communicable Diseases↗
PubMed2003

The developing role of peptide radiopharmaceuticals in the study of chronic inflammation: new techniques for novel therapeutic options.

Chronic inflammatory diseases usually lead to fibrosis of the target organ and consequent hypo function. They are often relapsing, invalidating and require life-long treatment. In this class of patients it is very important to try and achieve specific immune suppression to extinguish the immune process with the aim of preventing the disease, preventing or delaying complications and avoiding disease relapse, often requiring surgical intervention. It is important that, while attempting to improve the quality of life of these patients by means of anti-inflammatory drugs, side effects are reduced to a minimum via the use of specific immune therapies that block as selectively as possible the pathologic mechanism responsible for the disease. New therapeutic options are being developed for specific targeted therapies. Several trials are being performed to assess the efficacy and safety of this approach. All of them, however, rely on the clinical assessment of the patients to evaluate the effect of treatment. It would be important to use an objective and reliable method to highlight directly the immune process underlying the individual disease. This manuscript reviews the radiopharmaceuticals available or recently developed for imaging chronic inflammatory diseases and their use for therapy decision making and follow-up.

Animals↗
PubMed2002

Targeting cytokine/chemokine receptors: a challenge for molecular nuclear medicine.

Radiolabelled cytokines and chemokines are a group of radiopharmaceuticals that, by highlighting in vivo the binding to specific high-affinity receptors expressed on selected cell populations, allow the molecular and functional characterisation of immune-mediated processes Recently, several authors have described the use of radiolabelled cytokines and chemokines not only for imaging of inflammation and infection, but also as an approach to study in vivo the biology of primary and metastatic cancer cells. The latter avenue of research has been pursued particularly to help oncologists in therapeutic decision making and to follow up the efficacy of new immune therapies. In this paper we describe the characteristics of cytokines and chemokines, focussing on their role as radiopharmaceuticals for the imaging of cancer cells in vivo, a new challenge for molecular nuclear medicine.

Animals↗
PubMed2001

Peptide radiopharmaceuticals for diagnosis and therapy.

Radiolabelled peptides are an emerging class of radiopharmaceuticals that share chemical and biological properties. From the chemical point of view they have a poly-amino acid structure varying from 3 to more that 200 amino acids, and they are labelled with different isotopes directly or by a linker. Biologically, they bind to specific cell membrane receptors, thus providing in vivo histopathological information for diagnostic purposes, therapy follow-up or targeted radiotherapy. This paper reviews most of the radiolabelled peptides that have been tested in animals and humans in the fields of oncology, neurology, cardiology, inflammation/infection, atherosclerosis and thrombosis. A new classification is also proposed for peptides targeting tumour cells based on the biological function of target receptors. These tailored radiopharmaceuticals are the basis of the new era of "molecular nuclear medicine".

Arteriosclerosis↗
PubMed2000

The developing role of cytokines for imaging inflammation and infection.

The diagnosis of inflammatory processes is an important goal in medicine. In some cases the diagnosis is easy, based on the clinical history and the physical examination of the patient. Other cases are more difficult to diagnose because they are asymptomatic or with non-specific symptoms. Thus, several imaging techniques have been developed for the diagnosis of inflammatory processes, from the simple X-ray to the more sophisticated computerised tomography, magnetic resonance imaging and nuclear medicine scan. They provide different information and their role in different diseases will be discussed in this review with particular emphasis on the expanding field of the use of radiolabelled cytokines for imaging infection/inflammation. So far, IL-1, IL-1ra, IL-2, IL-6, IL-8, IL-10, IL-12 p40, G-CSF, IFN-gamma and EGF have been radiolabelled for in vivo targetting of different leukocyte subsets with promising results for their clinical use.

Animals↗
PubMed2000

Imaging active lymphocytic infiltration in coeliac disease with iodine-123-interleukin-2 and the response to diet.

Coeliac disease is diagnosed by the presence of specific antibodies and a jejunal biopsy showing mucosal atrophy and mononuclear cell infiltration. Mucosal cell-mediated immune response is considered the central event in the pathogenesis of coeliac disease, and untreated coeliac patients show specific features of T-cell activation in the small intestine. Here we describe the use of iodine-123-interleukin-2 scintigraphy in coeliac patients as a non-invasive tool for detection of lymphocytic infiltration in the small bowel and its use for therapy follow-up, and we demonstrate the specificity of binding of labelled-IL2 to activated lymphocytes by ex-vivo autoradiography of jejunal biopsies. 123I-IL2 was administered i.v. [74 MBq (2 mCi)], and gamma camera images were acquired after 1 h. Ten patients were studied with 123I-IL2 scintigraphy at diagnosis and seven were also investigated after 12-19 months of gluten-free diet. Results were expressed as target-to-background radioactivity ratios in six different bowel regions before and after the diet. At the time of diagnosis all patients showed a significantly higher bowel uptake of 123I-IL2 than normal subjects (P < 0.003 in all regions). A significant correlation was found between jejunal radioactivity and the number of IL2R + ve lymphocytes per millimetre of jejunal mucosa as detected by immunostaining of jejunal biopsy (r2 = 0.66; P = 0.008). Autoradiography of jejunal biopsies confirmed that labelled-IL2 only binds to activated T-lymphocytes infiltrating the gut mucosa. After 1 year of the diet, bowel uptake of 123I-IL2 significantly decreased in five out of six regions (P < 0.03), although two patients still had a positive IL2 scintigraphy in one region. We conclude that 123I-IL2 scintigraphy is a sensitive non-invasive technique for assessing in vivo the presence of activated mononuclear cells in the bowel of patients affected by coeliac disease. Unlike jejunal biopsy, this method provides information from the whole intestine and gives a non-invasive measure of the effectiveness of the gluten-free diet.

Adult↗
PubMed2000

123I-interleukin-2 scintigraphy for in vivo assessment of intestinal mononuclear cell infiltration in Crohn's disease.

UNLABELLED: Activated mononuclear cells expressing interleukin-2 (IL2) receptors (IL2-Rs) heavily infiltrate the Crohn's disease (CD) gut wall. A new technique for the in vivo detection of tissue infiltrating IL2-R positive (IL2R+ve) cells was developed based on 123I-IL2 scintigraphy. The aim of this study was to investigate whether 123I-IL2 accumulates in the CD gut wall in different phases of the disease and to evaluate the specificity of 123I-IL2 binding to activated IL2R+ve cells infiltrating the gut wall. METHODS: Fifteen patients with ileal CD (10 active and 5 inactive) and 10 healthy volunteers were studied by 123I-IL2 scintigraphy. Six patients with active CD were studied before and after 12 wk of steroid treatment. After scintigraphy, patients were followed up for 29-54 mo. Ex vivo autoradiography was performed to determine specificity of 125I-IL2 binding to IL2R+ve cells. For bowel scintigraphy, 123I-IL2 (75 MBq) was injected intravenously and gamma camera images were acquired after 1 h. Bowel radioactivity was quantified in 64 regions of interest (ROIs). RESULTS: Autoradiography showed specific binding of 125I-IL2 to IL2R+ve mononuclear cells infiltrating the CD gut wall. Intestinal 123I-IL2 uptake assessed by the number of positive ROIs was higher in patients with active or inactive CD than in healthy volunteers (P < 0.0001 and P = 0.03, respectively) and positively correlated with the CD activity index (P = 0.01). 123I-IL2 intestinal uptake significantly decreased in patients with CD in steroid-induced remission (P = 0.03). A significant correlation was observed between the number of positive ROIs and time to disease relapse. CONCLUSION: 123I-IL2 accumulates in the diseased CD gut wall by specific binding to IL2R+ve cells, infiltrating the involved tissues. 123I-IL2 scintigraphy may be an objective tool for the in vivo assessment of intestinal activated mononuclear cell infiltration.

Adult↗
PubMed1999

Characterization of a new form of inherited hypercholesterolemia: familial recessive hypercholesterolemia.

We previously described a Sardinian family in which the probands had a severe form of hypercholesterolemia, suggestive of familial hypercholesterolemia (FH). However, low density lipoprotein (LDL) receptor activity in fibroblasts from these subjects and LDL binding ability were normal. The characteristics of the pedigree were consistent with an autosomal recessive trait. Sitosterolemia and pseudohomozygous hyperlipidemia were ruled out. A second Sardinian kindred with similar characteristics was identified. Probands showed severe hypercholesterolemia, whereas their parents and grandparents were normolipidemic. FH, familial defective apoprotein (apo) B, sitosterolemia, and cholesteryl ester storage disease were excluded by in vitro studies. We addressed the metabolic basis of this inherited disorder by studying the in vivo metabolism of LDL in 3 probands from these 2 families. 125I-LDL turnover studies disclosed a marked reduction in the fractional catabolic rate (0.19+/-0.01 versus 0.36+/-0.03 pools per day, respectively; P<0.001) and a significant increase in the production rate [20.7+/-4.4 versus 14. 0+/-2.4 mg. kg-1. d-1, respectively; P<0.01] of LDL apoB in the probands compared with normolipidemic controls. We then studied the in vivo biodistribution and tissue uptake of 99mtechnetium-labeled LDL in the probands and compared them with those in normal controls and 1 FH homozygote. The probands showed a significant reduction in hepatic LDL uptake, similar to that observed in the FH homozygote. A reduced uptake of LDL by the kidney and spleen was also observed in all patients. Our findings suggest that this recessive form of hypercholesterolemia is due to a marked reduction of in vivo LDL catabolism. This appears to be caused by a selective reduction in hepatic LDL uptake. We propose that in this new lipid disorder, a recessive defect causes a selective impairment of LDL receptor function in the liver.

Adult↗
PubMed1999

Imaging of autoimmune diseases.

Autoimmune diseases represent a heterogeneous group of pathologies with a wide range of immunological changes and clinical presentations. The clinical onset of the disease commonly occurs when signs and symptoms of target tissue hypofunction appear; complications can also be present. The aim of an imaging diagnostic technique in this context is to correctly evaluate the disease extent and severity for appropriate treatment and to follow up the efficacy of therapy. In addition, identification of subjects at risk and the preclinical diagnosis may allow disease prevention. Ultrasound (US), conventional radiology and computed tomography (CT) are often used for a detailed morphological study of tissues involved; magnetic resonance (MRI) may also demonstrate biochemical and structural tissue changes. Nuclear medicine techniques are known for their sensitivity and specificity and in recent years an expanding field is represented by the development of radiolabelled receptor ligands. New radiopharmaceuticals able to bind in vivo to specific receptors have been introduced allowing the non invasive detection of changes in affected tissues. The relevant criteria to choose different diagnostic approaches in several autoimmune diseases are discussed in this review. In particular the role and contribution of nuclear medicine for the study of autoimmune diseases have been described.

Antibodies, Monoclonal↗
PubMed1998

Prognostic relevance of pancreatic uptake of technetium-99m labelled human polyclonal immunoglobulins in patients with type 1 diabetes.

Insulin-dependent type 1 diabetes (IDDM) is caused by the autoimmune destruction of insulin-producing beta cells. Approximately 10%-20% of patients may benefit from adjuvant immunotherapy upon diagnosis of the disease in order to protect residual beta-cell function. It has been suggested that this subgroup of patients differs from others by virtue of the presence of residual pancreatic inflammation and beta-cell function. In this study we have investigated to what extent technetium-99m-labelled human polyclonal immunoglobulins (99mTc-HIG) accumulate in the pancreas of IDDM patients at the time of diagnosis and 1 year thereafter, with a view to ascertaining whether HIG scintigraphy is useful for the identification of IDDM patients with residual pancreatic inflammation. Patients with recent-onset IDDM (n=15) were investigated at the time of diagnosis and 1 year later, and ten age- and sex-matched normal subjects were also studied. Gamma camera imaging and target to background ratio, analysed blind by three independent readers, were used to quantify the radioactivity in the pancreatic region and findings were correlated with metabolic, immunological and clinical parameters. Seven out of 15 newly diagnosed IDDM patients showed a significant accumulation of radiolabelled HIG in the pancreas (pancreas/bone ratio higher than the mean +2SD of normal subjects). One year after diagnosis, pancreatic accumulation of HIG was still detectable in most IDDM patients who were positive at the time of diagnosis. Six out of seven patients with positive scintigraphy had a partial clinical remission. These results indicate that HIG scintigraphy at the time of onset of diabetes identifies a subset of patients with residual beta-cell function who may benefit from adjuvant immunotherapy.

Adolescent↗
PubMed1997

The development of technetium-99m-labelled interleukin-2: a new radiopharmaceutical for the in vivo detection of mononuclear cell infiltrates in immune-mediated diseases.

We describe here a new method for labelling interleukin-2 (IL-2) in high specific activity with 99mTc for in vivo studies in man. Labelling was performed via a two-step reaction using an N3S bifunctional chelating agent. To optimise the reaction, factors affecting the incorporation of 99mTc into the N3S ligand were studied. The conjugation of the preformed N3S chelate ligand to IL-2 was then similarly optimised. Various strategies for purifying the 99mTc-IL-2 were explored including size-exclusion, ion-exchange, and several modes of reversed-phase chromatography. The radiochemical purity of the purified protein was determined by HPLC, ITLC, TCA precipitation, and SDS-PAGE. The receptor binding capacity of 99mTc-IL-2 was studied. Biodistribution studies in normal mice were performed with 99mTc-IL-2 purified using different techniques or labelled after prolonged storage and compared to 125I-IL-2.

Animals↗
PubMed1997

Radiopharmaceuticals for the study of inflammatory processes: a review.

Recent advances in our understanding of the pathophysiology of inflammatory processes at the molecular level, combined with progress in radiopharmaceutical sciences, has boosted the development of nuclear medicine techniques for the diagnosis of infection/inflammation. The use of radiolabelled white blood cells has been studied and evaluated in several pathologies and is still the reference method. Several alternative approaches, however, have been developed that may, in the future, improve the specificity and the ease of use of the technique. For the first time, a radiopharmaceutical that may distinguish between sterile and septic inflammation, 99Tcm-Infecton, has been developed. Also, monoclonal antibody fragments, cytokines and a variety of new synthetic peptides that bind specifically to granulocytes have been prepared. Particularly promising appears to be the detection of the expression of adhesion molecules by activated endothelium as a first-line technique for the detection of inflammatory foci. For the diagnosis of autoimmunity and chronic inflammatory processes, important progress has also been made. Autoimmunity can now be studied by in vivo detection of tissue-infiltrating activated lymphocytes by radiolabelled interleukin-2. A radiopharmaceutical for the diagnosis of monocyte infiltration, J001X, is also available, and the commercially available Octreoscan holds promise in autoimmune and chronic inflammatory diseases. The efforts of the scientific community have given us new perspectives in diagnostic nuclear medicine: easier techniques that promise better sensitivity and specificity are now also being tested for the study of new disease conditions. The results of the clinical trials now in progress will determine the future of this challenging and fascinating field and the role of nuclear medicine in the management of patients with infection/inflammation.

Antibodies, Monoclonal↗
PubMed1996

The effect of metformin on liver blood flow in vivo in normal subjects and patients with non insulin dependent diabetes.

We previously reported that metformin improves insulin-mediated glucose liver metabolism in patients with non insulin dependent diabetes (NIDDM). It is not clear whether this is a direct effect of metformin on liver metabolism or mediated by other mechanisms such as increased liver blood flow. In this respect it has recently been reported that metformin increases hepatic blood flow (HBF) in diabetic rats. The aim of this study was to evaluate whether the administration of metformin is associated with modifications in HBF in humans. Patients affected by NIDDM (n = 11) and normal subjects (n = 6) were studied. In the first protocol HBF was investigated in six overweight (BMI 27 +/- 2 Kg/m2) NIDDM patients and six normal subjects (age and BMI matched) already on metformin treatment before and 2 h after the administration of 500 mg metformin. In the second protocol HBF was investigated in obese (BMI 32 +/- 1 Kg/m2) NIDDM patients (n = 5) in good metabolic control before and after 15 days of metformin at the dose of 1 g daily. HBF was measured by intravenous injection of 3 mCi 99mTc-phytate. In both protocols no significant changes in HBF were observed following metformin administration either in NIDDM patients or normal subjects. No significant differences were observed in HBF between diabetic patients and normal subjects. These data indicate that metformin has no effect on HBF in man. The previously reported improvement of insulin mediated liver metabolism induced by metformin is likely to be a consequence of the direct effect of the drug at hepatocyte level which is independent of HBF modifications.

Adult↗
PubMed1996

Radiolabelled cytokines.

Cytokines are soluble factors that act as intercellular messenger between cells of the immune system. They act by binding to specific receptors that are normally poorly expressed on effector cells but in disease are upregulated following cell activation. Several cytokine/cytokine receptor systems operate in infection, autoimmunity, cancer and other pathological conditions. This enhanced receptor expression can form a target for the diagnosis of the disease process. Many cytokines have characteristics which favour their use as radiopharmaceuticals; these include a relatively low molecular weight, short half life and rapid plasma clearance, binding of high affinity to specific receptors, ready availability due to recombinant technology and lack of immunogenicity. Radiolabelled cytokines are therefore a promising class of peptide radiopharmaceuticals that may have diagnostic potential in a number of pathological conditions.

Animals↗