Nuclear medicine offers several techniques and procedures to image infection, but radiolabelled autologous white blood cells (WBCs) are still the gold standard. These cells are usually labelled with 111In or 99mTc bound to a hydrophobic... more
Nuclear medicine offers several techniques and procedures to image infection, but radiolabelled autologous white blood cells (WBCs) are still the gold standard. These cells are usually labelled with 111In or 99mTc bound to a hydrophobic chelating agent that allows these isotopes to pass through the plasma membrane and enter in the cytoplasm. The most common compound in Europe is HMPAO that efficiently chelates 99mTc. However, up to 20–40% of the complex is released from the cells in the first few hours. The aim of this study was to radiolabel a new compound, (S3CPh)2 (S2CPh)-complex (SSS-complex) with 99mTc and compare its binding kinetics and specificity for WBC with HMPAO. The SSS-complex was labelled with 99mTc and analysed by iTLC and RP-HPLC. In vitro quality controls included a stability assay in serum and saline. Results showed a labelling efficiency of 95 ± 1.2% and 98 ± 1.4% for 99mTc-SSS-complex and 99mTc-HMPAO, respectively (p=ns). 99mTc-SSS-complex was stable in serum an...
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Aim. Aim of the present study was to compare in vitro the labelling efficiency (LE) and cell viability (TBE) of autologous leukocytes labelled with 99mTc-SnF2 and 99mTc-HMPAO, and to evaluate the quantity and quality of spontaneously... more
Aim. Aim of the present study was to compare in vitro the labelling efficiency (LE) and cell viability (TBE) of autologous leukocytes labelled with 99mTc-SnF2 and 99mTc-HMPAO, and to evaluate the quantity and quality of spontaneously released 99mTc (SR) from labelled cells at several time points after labelling. Methods. A total of 14 patients with different diseases and 18 normal subjects were included in this study. A blood sample was collected from each patient; purified autologous leukocytes were divided into 2 samples and labelled with 99mTC-SnF2 and 99mTC-HMPAO. LE was evaluated at the end of labelling and TBE and SR were evaluated at 10 min and 1 h, 2 h and 4 h after labelling. Results. LE of 99mTc-SnF2-WBC was higher than 99mTc-HMPAO-WBC (61.2±18.7% and 43.3±11.3; p< 0.0001) and we found an inverse correlation between blood glucose and labelling efficiency for both methods (p=0.02). Minimal differences were also observed between 2 methods after 10 min and 1 h, as far as the cell viability is concerned. The percentage of radioactivity spontaneously released from 99mTc-SnF2-WBC was significantly higher compared to 99mTc-HMPAO-WBC at each time point. Radioactivity released from labelled cells was predominantly 99mTC-SnF2 and 99mTC-HMPAO With few free 99mTc (<20%). Conclusion. Both radiopharmaceuticals are not toxic for WBC. Labelling with 99mTc-SnF2 give a higher LE than with 99mTc-HMPAO; however, radiolabelled colloids are more released from labelled cells over a period of 4 h. While 99mTc-HMPAO is physiological excreted into gastrointestinal tract, 99mTC-SnF2 can be re-uptaken in vivo by reticulo-endothelial cells of liver and spleen. These findings suggest that 99mTc-SnF2-WBC might be better than 99mTc-HMPAO-WBC for studying inflammatory bowel diseases
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Monoclonal antibodies, which include murine, chimeric, humanized and fully human antibodies, bind to their target receptors with high affinity and specificity. In the last two decades several different monoclonal antibodies have been... more
Monoclonal antibodies, which include murine, chimeric, humanized and fully human antibodies, bind to their target receptors with high affinity and specificity. In the last two decades several different monoclonal antibodies have been approved by the Food and Drug Administration for therapeutic purposes, and some of these and others have also been radiolabelled for diagnostic and therapeutic purposes. This field is in continuous evolution and this overview highlights the role of radiolabelled antibodies in research and clinical setting.
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This pilot study reports on the uptake of (123)I-interleukin 2 (IL-2) in metastatic renal cell carcinoma (MRCC) patients and its relationship to prognostic factors of response or failure of MRCC to cytokines treatment. Nine consecutive... more
This pilot study reports on the uptake of (123)I-interleukin 2 (IL-2) in metastatic renal cell carcinoma (MRCC) patients and its relationship to prognostic factors of response or failure of MRCC to cytokines treatment. Nine consecutive patients with MRCC underwent an (123)I-IL-2 scan (6 male and 3 female; mean age 64 years; range 51-78). Uptake in metastases was related to a summed score of 4 independent factors, predictive of rapid progression under cytokine treatment as defined by Negrier et al. Four patients presented with metastases at one site, 4 at 2 sites and one patient at 3 different sites. Summed scores were: 5 patients had a summed score of 1; 3 a summed score of 2 and 1 patient a summed score of 3. Uptake of (123)I-IL-2 by tumor tissue was found in only 2 patients. Uptake occurred in 1 patient with a summed score of 3 and in 1 with a summed score of 2. In this small series of patients with MRCC, (123)I-IL-2 uptake was found in tumors of 2 patients who less likely will be...
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The diurnal variation of peripheral white cells and in particular of different lymphocyte subsets has been investigated in 11 normal subjects. Monoclonal antibodies (Mab) phenotyping total T lymphocytes (UCHT1), cytotoxic/suppressor... more
The diurnal variation of peripheral white cells and in particular of different lymphocyte subsets has been investigated in 11 normal subjects. Monoclonal antibodies (Mab) phenotyping total T lymphocytes (UCHT1), cytotoxic/suppressor (UCHT4), helper T cells (Leu 3a), B lymphocytes (231) and K/NK cells (H25) have been used. In addition to the traditional parametric statistics, the chronobiological approach of cosinor was adopted in order to inferentially obtain the waveform covering the 24-hr period. Cosinor analysis validated the existence of a significant rhythm for leucocytes (p = 0.04, lymphocytes (p = 0.03), and Leu 3a positive cells (p = 0.04). The best fitting period was equal to 28 hr. No circadian rhythm was documented for lymphocyte subsets positive for Mab UCHT4, 231, H25, by testing the variability with a frequency ranging from 1 cycle every 12hr to 1 cycle every 28 hr. By the non-inferential analysis of temporal curves, a significant peak of Leu 3a positive cells at 20.00...
Research Interests: Biology, Biometry, Medicine, Humans, Circadian Rhythm, and 6 moreMale, Monoclonal Antibodies, Adult, Lymphocytes, Leukocytes, and Lymphocyte
Acute inflammatory response to lipopolysaccharide (LPS) exposure is typically associated with cardiac myocyte apoptosis, which is difficult to quantify because of heart tissue specificity. We report here that radioiodinated Annexin V... more
Acute inflammatory response to lipopolysaccharide (LPS) exposure is typically associated with cardiac myocyte apoptosis, which is difficult to quantify because of heart tissue specificity. We report here that radioiodinated Annexin V (I-AnxV), a specific ligand of phosphatidylserine exposed by apoptotic cells, allows tissue detection of apoptosis in LPS-treated rat hearts. Heart I-AnxV uptake was significantly increased in all cardiac territories of LPS-treated rats. In contrast, I-human serum albumin myocardial uptake was only slightly increased in LPS-treated rat hearts, suggesting limited changes in vascular protein permeability. Autoradiography of endotoxin-treated rat heart sections with I-AnxV in association with deoxynucleotidyl transferase-mediated dUTP-biotin nick-end labeling and caspase 3 staining allows identification of double positive cardiac myocytes. Inhibition of apoptosis by caspase inhibitors (i.e., ZVAD.fmk and DEVD.cmk) reduced I-AnxV myocardial uptake in LPS-treated rats. Eventually, endotoxin-treated rats displayed pathological uptake of Tc-annexin in the cardiac mediastinal region whereas zVAD.fmk reduced Tc-annexin mediastinal uptake. Our results show that radioactive I-AnxV signal emerging from LPS-treated rat hearts could be related to the activation of caspase-dependent apoptotic pathway in cardiac myocytes.
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Research Interests: Chemistry, Chromatography, Flow Cytometry, Nuclear medicine, Medicine, and 15 moreHumans, Mice, Animals, Male, Clinical Sciences, High Pressure Liquid Chromatography, Biodistribution, Rats, Radiolabelling, Lymphocytes, Recombinant Proteins, Inflammation imaging, Interleukin, Tissue distribution, and Niacinamide
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Research Interests: Computed Tomography, Decision Making, Medicine, Clinical Practice, Humans, and 15 moreFemale, Male, Clinical Sciences, Aged, Middle Aged, Adult, Group, Bone Metastases, Lymph Node, Positive predictive value, Graves Disease, Edetic Acid, False Positive, Local Recurrence, and Negative predictive value
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A 1-year open randomized controlled multicentre trial was carried out on 90 patients with recent onset (< 4 weeks) insulin-dependent diabetes (IDDM) to compare the effect of nicotinamide (NCT) with the combination NCT and low dose... more
A 1-year open randomized controlled multicentre trial was carried out on 90 patients with recent onset (< 4 weeks) insulin-dependent diabetes (IDDM) to compare the effect of nicotinamide (NCT) with the combination NCT and low dose cyclosporin (CyA) on clinical remission and optimization of metabolic control during the first year from diagnosis. Three groups of patients were randomly assigned to receive for 12 months either NCT 25 mg kg-1 day-1 (n = 30) or NCT 25 mg kg-1 day-1 + CyA 5 mg kg-1 day-1 (n = 30), the latter adjusted to maintain 12 whole blood trough levels of 83 nmol l-1; a third group of patients (n = 30) receiving insulin only acted as a control group for spontaneous remission and metabolic control. Clinical remission (i.e. suspension of insulin therapy with normal metabolic parameters for more than 2 weeks according to the International Diabetes Immunotherapy Group) was achieved at 3 months in 6/30 NCT treated patients and in 1/30 NCT + CyA treated patient (p = 0.05); no remission was observed in control patients. At 6 months the number of patients achieving remission in each group was 4/29, 3/27, and 1/29, respectively (p = NS). One year after diagnosis 4/27 NCT treated, 2/25 NCT+CyA treated but 0/28 of the control patients were in remission (NCT vs control p = 0.05). Clinical remission lasted longer (7 +/- 3 SD months) in NCT treated patients than in NCT+CyA treated or control patients (p < 0.02).(ABSTRACT TRUNCATED AT 250 WORDS)
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Positive experiences with intraarticular infliximab have been reported in patients with rheumatoid arthritis, ankylosing spondylitis, and... more
Positive experiences with intraarticular infliximab have been reported in patients with rheumatoid arthritis, ankylosing spondylitis, and Behcet's disease. We used intraarticular infliximab to treat resistant knee monarthritis in a patient with spondylarthropathy. Clinical and laboratory improvement was associated with improvement in scintigraphic findings. This approach is less expensive than intravenous administration of infliximab. We suggest that selection of candidates for this innovative therapy should be guided by anti-tumor necrosis factor alpha scintigraphy.
Research Interests: Immunology, Treatment Outcome, Rheumatoid Arthritis, Medicine, Humans, and 12 moreMale, Monoclonal Antibodies, Radionuclide imaging, Arthritis, Ankylosing Spondylitis, Clinical Sciences, Adult, Public health systems and services research, Tumor necrosis factor-alpha, Technetium, Knee Joint, and Infliximab
Background To investigate the cause of lymphopenia in patients with newly diagnosed COVID-19, we measured [18F]FDG uptake in several tissues, including the ileum, right colon, and caecum at diagnosis and after recovery and correlated... more
Background To investigate the cause of lymphopenia in patients with newly diagnosed COVID-19, we measured [18F]FDG uptake in several tissues, including the ileum, right colon, and caecum at diagnosis and after recovery and correlated these measurements with haematological parameters. Methods We studied, by [18F]FDG PET/CT, 18 newly diagnosed patients with COVID-19. Regions of interest were drawn over major organs and in the terminal ileum, caecum, and right colon, where the bowel wall was evaluable. Five patients were re-examined after recovery, and three of them also performed a white blood cell scan with 99mTc-HMPAO-WBC on both occasions. Complete blood count was performed on both occasions, and peripheral blood lymphocyte subsets were measured at diagnosis. Data were analysed by a statistician. Results Patients had moderate severity COVID-19 syndrome. Basal [18F]FDG PET/CT showed focal lung uptake corresponding to hyperdense areas at CT. We also found high spleen, ileal, caecal, ...
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The purpose of this study was to compare the effect of indium oxine and indium-tropolone complexes (nonradiolabeled) on the function of isolated human lymphocytes. Peripheral lymphocytes were obtained from 15 normal volunteers and... more
The purpose of this study was to compare the effect of indium oxine and indium-tropolone complexes (nonradiolabeled) on the function of isolated human lymphocytes. Peripheral lymphocytes were obtained from 15 normal volunteers and incubated with indium oxine or indium tropolone according to the standard techniques currently used when cells are radiolabeled for subsequent in vivo studies. The phytohemagglutinin-induced (PHA) lymphocyte
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We evaluated the sensitivity of 111In-Octreotide scintigraphy in the diagnosis of pancreatic insulinoma in a selected number of patients. In addition, we compared the results of scintigraphy with those of other conventional diagnostic... more
We evaluated the sensitivity of 111In-Octreotide scintigraphy in the diagnosis of pancreatic insulinoma in a selected number of patients. In addition, we compared the results of scintigraphy with those of other conventional diagnostic techniques. Seven patients with surgically confirmed insulinoma (< 1.5 cm in diameter) of the pancreas were studied. Before surgery, patients underwent arteriography with Ca-gluconate, CT scan, and 111In-Octreotide scintigraphy. 111In-Octreotide scintigraphy showed a higher diagnostic specificity (85%) than selective arteriography (83%) or CT scan (57%). We conclude that 111In-Octreotide scintigraphy should always be performed before surgery in cases of pancreatic insulinoma and that a SPECT acquisition should be performed both 6 and 24 hours post-injection in order to increase the diagnostic sensitivity of the test.
Research Interests: Adolescent, Medicine, Humans, Female, Male, and 13 moreDiagnostic Imaging, Insulinoma, Clinical Sciences, Angiography, Aged, Middle Aged, Single Photon Emission Computed Tomography, Adult, Radiopharmaceuticals, Sensitivity and Specificity, X ray Computed Tomography, Octreotide, and Pancreatic neoplasms
This review examines the association between retroviruses and diabetes in the mouse model, the role of retroviruses in the pathogenesis of Type 1 diabetes and the mechanisms by which retroviruses can induce an autoimmune reaction. Three... more
This review examines the association between retroviruses and diabetes in the mouse model, the role of retroviruses in the pathogenesis of Type 1 diabetes and the mechanisms by which retroviruses can induce an autoimmune reaction. Three putative mechanisms are considered: the expression of retroviral protein(s) on the beta-cell surface as the first step in immune response against beta cells; the homology of a retroviral product with a self antigen inducing a cross-reacting autoimmune response (molecular mimicry); and a retroviral product showing homology with interleukin-2 and inducing T-cell activation against beta-cell antigens and loss of tolerance. These findings are discussed for their possible implications in the pathogenesis of human Type 1 diabetes.
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Activated mononuclear cells expressing interleukin 2 (IL2) receptors (IL2R) heavily infiltrate the Crohn's Disease (CD) gut wall. A new technique for the" in vivo" detection of tissue infiltrating IL2R positive (IL2R+ ve)... more
Activated mononuclear cells expressing interleukin 2 (IL2) receptors (IL2R) heavily infiltrate the Crohn's Disease (CD) gut wall. A new technique for the" in vivo" detection of tissue infiltrating IL2R positive (IL2R+ ve) cells was developed based on 123I-...
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... [12] MD Coltrera, J. Wang, PL Porter and AM Gown. Cancer Res., 55 12 (1995), p. 2703. [13] A. Kranz, T. Mettfeldt and J. Waltenberger. Int. J. Cancer, 84 3 (1999), p. 293. [14] DN McMillan, NM Kernohan and ME Flett et al.. Int. J.... more
... [12] MD Coltrera, J. Wang, PL Porter and AM Gown. Cancer Res., 55 12 (1995), p. 2703. [13] A. Kranz, T. Mettfeldt and J. Waltenberger. Int. J. Cancer, 84 3 (1999), p. 293. [14] DN McMillan, NM Kernohan and ME Flett et al.. Int. J. Cancer, 60 6 (1995), p. 766. ...
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Radiolabelled cytokines and chemokines are a new group of radiopharmaceuticals. These, by binding to specific receptors expressed on selected cell populations, enable the histological and functional characterization of immune-mediated... more
Radiolabelled cytokines and chemokines are a new group of radiopharmaceuticals. These, by binding to specific receptors expressed on selected cell populations, enable the histological and functional characterization of immune-mediated processes, in vivo. Clinical studies have demonstrated the efficacy of using this type of scintigraphy in detecting sites of acute inflammation (infection) and chronic (T-cell-mediated) inflammation. Recent studies are focusing on
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Thyroglobulin (Tg) is a key marker in the follow-up of differentiated thyroid cancer (DTC). Diagnostic accuracy of serum Tg is higher after TSH stimulation than during thyroxine treatment. However, some studies suggest that TSH... more
Thyroglobulin (Tg) is a key marker in the follow-up of differentiated thyroid cancer (DTC). Diagnostic accuracy of serum Tg is higher after TSH stimulation than during thyroxine treatment. However, some studies suggest that TSH stimulation could be not necessary in a large part of patients, if Tg is measured by high sensitive assay under replacement therapy. The aim of this study was to evaluate the need of Tg stimulation test in DTC followed-up by sensitive Tg assay. In a prospective multicenter explorative study, 68 low or high risk patients underwent Tg measurement on thyroxine (ON-LT4-Tg) and after LT4 withdrawal (OFF-LT4-Tg). Undetectable ON-LT4-Tg and OFF-LT4-Tg values (i. e.,&amp;amp;amp;amp;amp;amp;amp;amp;lt;0.15 ng/ml) were found in 56/68 patients, all with negative imaging workup. Twelve subjects had skewed OFF-LT4-Tg: 8 cases had increased ON-LT4-Tg and local recurrence (n=6), distant metastasis (n=1), or benign thyroglossal duct (n=1); the remaining 4 patients had undetectable ON-T4-Tg but detectable OFF-LT4-Tg and neck metastasis was recorded in one of these. By ROC analysis, the most accurate cutoff for ON-LT4-Tg and OFF-LT4-Tg were set at 0.23 ng/ml and 0.70 ng/ml, respectively. A positive ON-LT4-Tg value accurately predicts a positive stimulation test and confers an Odds Ratio of 464 (95% CI from 26.3 to 8 173.2, p&amp;amp;amp;amp;amp;amp;amp;amp;lt;0.0001) to have persistent/recurrent disease. This study shows that DTC patients with ON-LT4-Tg below 0.23 ng/ml by our high sensitive assay should be considered disease free and they can avoid Tg stimulation test. High sensitive Tg assays should be used to better manage DTC patients.
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This study compared serum thyroglobulin measurement and whole-body scans in the post-surgical follow-up of patients with differentiated thyroid carcinoma. Thyroglobulin levels were measured in 61 patients receiving L-thyroxine therapy... more
This study compared serum thyroglobulin measurement and whole-body scans in the post-surgical follow-up of patients with differentiated thyroid carcinoma. Thyroglobulin levels were measured in 61 patients receiving L-thyroxine therapy after thyroidectomy, and again after ...
Research Interests: Nuclear medicine, Sensitivity Analysis, Medicine, Nuclear, Humans, and 15 moreBeta decay, Female, Male, Follow-up studies, Thyroxine, Clinical Sciences, Papillary Squamous Cell Carcinoma, Thyroidectomy, Whole Body, Thyroglobulin, Adenocarcinoma, Combined Modality Therapy, Neoplasm metastasis, Differentiated thyroid carcinoma, and Thyroid Neoplasms
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... more
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.
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The current gold standard for imaging infection is radiolabeled white blood cells. For reasons of safety, simplicity and cost, it would be desirable to have a receptor-specific ligand that could be used for imaging infection and that... more
The current gold standard for imaging infection is radiolabeled white blood cells. For reasons of safety, simplicity and cost, it would be desirable to have a receptor-specific ligand that could be used for imaging infection and that would allow a differential diagnosis between sterile and septic inflammatory processes. Ligands tested for this purpose include labeled peptides ((99m)Tc-labeled f-Met-Leu-Phe, (123)I-IL-1ra, (99m)Tc-IL-8, (99m)Tc-P483H, (99m)Tc-P1827DS, (99m)Tc-C5a-des-Arg, (99m)Tc-RP517, (11)In-DPC11870-11), human polyclonal antibodies, monoclonal antibodies, antibody fragments, antimicrobial agents (ciprofloxacin, sparfloxacin, ceftizoxime, isoniazid, ethambutol, fluconazole, all labeled with (99m)Tc), antimicrobial peptides and bacteriophages. Radiolabeled antibodies represent a valid alternative to labeled white blood cells under specific conditions and indications. Radiolabeled antibiotics and antimicrobial peptides are promising candidates for an infection-specific radiopharmaceutical. However, at present we still need to investigate many basic aspects to better understand the mechanisms of binding and accumulation of this class of radiopharmaceuticals to bacteria.
Research Interests: Biology, Medicine, Humans, Animals, Infection, and 14 moreDifferential Diagnosis, Sterilization, Antimicrobial Peptide, Gold Standard, Current, Radioligand Assay, Monoclonal Antibody, Radiopharmaceuticals, Protein Binding, Ligands, Leukocytes, White Blood Cell, Pharmacology and pharmaceutical sciences, and Antimicrobial agent
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Research Interests: Biochemistry, Chemistry, Medicine, Humans, Insulin, and 15 morePlacenta, Beta decay, Protein Conformation, Insulin Receptor, Amino Acid Sequence, Membrane Protein, Protein Denaturation, Ligands, Binding Site, Conformational Change, Biochemistry and cell biology, Molecular Structure, Molecular Sequence Data, Receptor Insulin, and Medical biochemistry and metabolomics
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This article reviews the latest diagnostic advances in the evaluation of the CD, including functional studies on intestinal motility and molecular characterization of the inflammatory process at the level of the involved bowel. Molecular... more
This article reviews the latest diagnostic advances in the evaluation of the CD, including functional studies on intestinal motility and molecular characterization of the inflammatory process at the level of the involved bowel. Molecular changes related to inflammation of the intestinal wall may be evaluated by different MRI techniques, including diffusion-weighted imaging, perfusion weighted imaging, in vivo spectroscopy, molecular imaging, and fusion imaging (PET-MRI).