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1.
Arch Endocrinol Metab ; 68: e230181, 2024 May 17.
Artigo em Inglês | MEDLINE | ID: mdl-38788146

RESUMO

Hemangioblastomas associated with von Hippel-Lindau (VHL) disease are frequently multiple and recur during prolonged follow-up. Currently, no systemic treatment is available for these tumors. Recent studies have shown the expression of somatostatin receptors in these types of hemangioblastomas. Notably, increased somatostatin receptor expression in a tumor, as determined by peptide-receptor radionuclide imaging, is a predictive factor of response to treatment with somatostatin analogs and peptide-receptor radionuclide therapy. The aim of this study was to describe the case of a patient with increased expression of somatostatin receptors in a suprasellar hemangioblastoma associated with VHL disease and conduct a literature review on somatostatin receptor expression in patients with VHL-associated hemangioblastomas. We describe herein the case of a 51-year-old man with VHL disease who had a suprasellar hemangioblastoma detected on magnetic resonance imaging. Peptide-receptor radionuclide imaging using gallium-68-DOTATOC (68Ga-DOTATOC) identified increased expression of somatostatin receptors in the suprasellar hemangioblastoma, along with multiple pancreatic neuroendocrine tumors and bilateral pheochromocytomas. The patient was treated for 1 year with lanreotide, a somatostatin analog. A repeat 68Ga-DOTATOC 1 year after starting lanreotide revealed decreased radiotracer uptake by the hemangioblastoma, consistent with a metabolic response. The presence of somatostatin receptors in hemangioblastomas associated with VHL disease is a novel finding. The decreased expression of these receptors after treatment with a somatostatin analog, as described in the present case, positions the somatostatin receptor as a new target for novel diagnostic, therapeutic, and follow-up opportunities in patients with VHL disease.


Assuntos
Hemangioblastoma , Receptores de Somatostatina , Doença de von Hippel-Lindau , Humanos , Hemangioblastoma/diagnóstico por imagem , Doença de von Hippel-Lindau/complicações , Receptores de Somatostatina/análise , Receptores de Somatostatina/metabolismo , Masculino , Pessoa de Meia-Idade , Octreotida/uso terapêutico , Octreotida/análogos & derivados , Neoplasias Cerebelares/diagnóstico por imagem , Neoplasias Cerebelares/tratamento farmacológico , Seguimentos , Imageamento por Ressonância Magnética , Compostos Radiofarmacêuticos/uso terapêutico
2.
Arch. endocrinol. metab. (Online) ; 68: e230181, 2024. tab, graf
Artigo em Inglês | LILACS-Express | LILACS | ID: biblio-1556948

RESUMO

SUMMARY Hemangioblastomas associated with von Hippel-Lindau (VHL) disease are frequently multiple and recur during prolonged follow-up. Currently, no systemic treatment is available for these tumors. Recent studies have shown the expression of somatostatin receptors in these types of hemangioblastomas. Notably, increased somatostatin receptor expression in a tumor, as determined by peptide-receptor radionuclide imaging, is a predictive factor of response to treatment with somatostatin analogs and peptide-receptor radionuclide therapy. The aim of this study was to describe the case of a patient with increased expression of somatostatin receptors in a suprasellar hemangioblastoma associated with VHL disease and conduct a literature review on somatostatin receptor expression in patients with VHL-associated hemangioblastomas. We describe herein the case of a 51-year-old man with VHL disease who had a suprasellar hemangioblastoma detected on magnetic resonance imaging. Peptide-receptor radionuclide imaging using gallium-68-DOTATOC (68Ga-DOTATOC) identified increased expression of somatostatin receptors in the suprasellar hemangioblastoma, along with multiple pancreatic neuroendocrine tumors and bilateral pheochromocytomas. The patient was treated for 1 year with lanreotide, a somatostatin analog. A repeat 68Ga-DOTATOC 1 year after starting lanreotide revealed decreased radiotracer uptake by the hemangioblastoma, consistent with a metabolic response. The presence of somatostatin receptors in hemangioblastomas associated with VHL disease is a novel finding. The decreased expression of these receptors after treatment with a somatostatin analog, as described in the present case, positions the somatostatin receptor as a new target for novel diagnostic, therapeutic, and follow-up opportunities in patients with VHL disease.

3.
J Nucl Cardiol ; 30(6): 2702-2711, 2023 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-37605061

RESUMO

BACKGROUND: Chagas heart disease (CHD) is characterized by progressive myocardial inflammation associated with myocardial fibrosis and segmental abnormalities that may lead to malignant ventricular arrhythmia and sudden cardiac death. This arrhythmia might be related to the persistence of parasitemia or inflammation in the myocardium in late-stage CHD. Positron emission tomography/computed tomography (PET/CT) has been used to detect myocardial inflammation in non-ischemic cardiomyopathies, such as sarcoidosis, and might be useful for risk prediction in patients with CHD. METHODS AND RESULTS: Twenty-four outpatients with chronic CHD were enrolled in this prospective cross-sectional study between May 2019 and March 2022. The patients were divided into two groups: those with sustained ventricular tachycardia and/or aborted sudden cardiac death who required implantable cardioverter-defibrillators, and those with the same stages of CHD and no complex ventricular arrhythmia. Patients underwent 18F-fluorodeoxyglucose (18F-FDG) and 68Ga-DOTATOC PET/CT, and blood samples were collected for qualitative parasite assessment by polymerase chain reaction. Although similar proportions of patients with and without complex ventricular arrhythmia showed 18F-FDG and 68Ga-DOTATOC uptake, 68Ga-DOTATOC corrected SUVmax was higher in patients with complex arrhythmia (3.4 vs 1.7; P = .046), suggesting that inflammation could be associated with the presence of malignant arrhythmia in the late stages of CHD. We also detected Trypanosoma cruzi in both groups, with a nonsignificant trend of increased parasitemia in the group with malignant arrhythmia (66.7% vs 33.3%). CONCLUSION: 18F-FDG and 68Ga-DOTATOC uptake on PET/CT may be useful for the detection of myocardial inflammation in patients with Chagas cardiomyopathy, and 68Ga-DOTATOC uptake may be associated with the presence of malignant arrhythmia, with potential therapeutic implications.


Assuntos
Doença de Chagas , Cardiopatias , Miocardite , Humanos , Tomografia por Emissão de Pósitrons combinada à Tomografia Computadorizada , Fluordesoxiglucose F18 , Tomografia por Emissão de Pósitrons/métodos , Radioisótopos de Gálio , Estudos Transversais , Parasitemia , Estudos Prospectivos , Miocardite/diagnóstico por imagem , Arritmias Cardíacas/diagnóstico por imagem , Inflamação/diagnóstico por imagem , Morte Súbita Cardíaca , Doença de Chagas/complicações , Doença de Chagas/diagnóstico por imagem
4.
J Clin Immunol ; 43(7): 1496-1505, 2023 10.
Artigo em Inglês | MEDLINE | ID: mdl-37294518

RESUMO

PURPOSE: Myocardial injury is common in hypertensive patients with 2019 coronavirus disease (COVID-19). Immune dysregulation could be associated to cardiac injury in these patients, but the underlying mechanism has not been fully elucidated. METHODS: All patients were selected prospectively from a multicenter registry of adults hospitalized with confirmed COVID-19. Cases had hypertension and myocardial injury, defined by troponin levels above the 99th percentile upper reference limit, and controls were hypertensive patients with no myocardial injury. Biomarkers and immune cell subsets were quantified and compared between the two groups. A multiple logistic regression model was used to analyze the associations of clinical and immune variables with myocardial injury. RESULTS: The sample comprised 193 patients divided into two groups: 47 cases and 146 controls. Relative to controls, cases had lower total lymphocyte count, percentage of T lymphocytes, CD8+CD38+ mean fluorescence intensity (MFI), and percentage of CD8+ human leukocyte antigen DR isotope (HLA-DR)+ CD38-cells and higher percentage of natural killer lymphocytes, natural killer group 2A (NKG2A)+ MFI, percentage of CD8+CD38+cells, CD8+HLA-DR+MFI, CD8+NKG2A+MFI, and percentage of CD8+HLA-DR-CD38+cells. On multivariate regression, the CD8+HLA-DR+MFI, CD8+CD38+MFI, and total lymphocyte count were associated significantly with myocardial injury. CONCLUSION: Our findings suggest that lymphopenia, CD8+CD38+MFI, and CD8+HLA-DR+MFI are immune biomarkers of myocardial injury in hypertensive patients with COVID-19. The immune signature described here may aid in understanding the mechanisms underlying myocardial injury in these patients. The study data might open a new window for improvement in the treatment of hypertensive patients with COVID-19 and myocardial injury.


Assuntos
Linfócitos T CD8-Positivos , COVID-19 , Adulto , Humanos , ADP-Ribosil Ciclase 1 , COVID-19/complicações , Antígenos HLA-DR , Biomarcadores , Ativação Linfocitária
5.
Future Sci OA ; 8(4): FSO793, 2022 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-35369279

RESUMO

Aim: Intracerebral hemorrhage (ICH) has limited therapeutic options. We have shown that an intravenous injection of human umbilical cord-derived mesenchymal stromal cells (hUC-MSC) 24 h after an ICH in rats reduced the residual hematoma volume after a moderate hemorrhage but was inefficient in severe ICH. Here, we investigated whether a treatment in the hyperacute phase would be more effective in severe ICH. Materials & methods: Wistar rats were randomly selected to receive an intravenous injection of hUC-MSC or the vehicle 1 h after a severe ICH. Results: The hyperacute treatment with hUC-MSC did not affect the 22-day survival rate, the motor function or the residual hematoma volume. Conclusion: These results indicate the need for optimization of hUC-MSC-based therapies for severe ICH.

6.
Int. j. cardiovasc. sci. (Impr.) ; 34(6): 702-713, Nov.-Dec. 2021. tab, graf
Artigo em Inglês | LILACS-Express | LILACS | ID: biblio-1421760

RESUMO

Abstract Cardiovascular diseases are among the leading causes of mortality and morbidity in the world. In different cardiac diseases, the neuronal function of the heart is impaired. Nevertheless, the development of a simple method to assess the autonomic effects on the heart and/or autonomic dysfunction is a challenge. The evaluation of autonomic innervation in cardiac diseases has helped to improve the knowledge of the pathophysiology of these conditions, as well as to provide information on their prognosis. Single photon emission computed tomography (SPECT) and positron emission tomography (PET) are currently the only imaging methods that allow in vivo assessment of cardiac innervation. The majority of SPECT and PET radiotracers evaluate sympathetic neuronal integrity using presynaptic imaging agents that are either labeled as endogenous transmitters or analogues. Postsynaptic imaging agents have also been developed to study sympathetic neuronal integrity, as well as tracers to investigate the parasympathetic nervous system. These methods may be used to analyze the innervation of the heart and allow for early detection of abnormalities caused by, for example, ischemia, heart failure, cardiomyopathies, cardiotoxicity, and arrhythmogenic disorders. This review provides an overview of cardiac innervation evaluation and their application in the assessment of heart disease.

7.
Am J Nucl Med Mol Imaging ; 11(4): 300-306, 2021.
Artigo em Inglês | MEDLINE | ID: mdl-34513283

RESUMO

Coronavirus disease 2019 (COVID-19) pathology is associated with neoangiogenesis and interstitial pneumonia. 68Ga-PSMA-11-PET/CT is able to image in vivo PSMA (Prostate-Specific Membrane Antigen) expression on both prostate cancer (PCa) cells and neovasculature endothelial cells. The aim of the case series was to explore pulmonary PSMA expression not related to cancer in patients with PCa and concomitant COVID-19. In this retrospective, multicenter case series, patients who underwent 68Ga-PSMA-11-PET/CT for PCa and concomitant proven COVID-19 infection were analyzed. Patients were stratified according to 68Ga-PSMA-11 intensity of uptake in the lung (SUVmax). Low uptake: < blood pool; mild-to-moderate uptake: > blood pool and < liver; intense uptake: > liver. Potential correlation between pulmonary 68Ga-PSMA-11 uptake not related to PCa and CT patterns typical for COVID-19 was assessed. Nine patients were included, all of them presenting abnormal 68Ga-PSMA-11 uptake, at different grades: 2/9 low, 6/9 mild-to-moderate, 1/9 high. Uptake distribution was generally bilateral, peripheral and posterior, positively matching with ground-glass CT alterations in 7/9 (78%) patients, while mismatch was observed in 2/9 (22%). 1/9 patients presented PCa lung metastases at 68Ga-PSMA-11. 68Ga-PSMA-11-PET/CT detected increased PSMA uptake within the lung, not related to PCa, matching with CT typical COVID-19 patterns in almost all patients. Further studies are needed to evaluate the role of 68Ga-PSMA-11 PET in COVID-19 patients and the potential role of PSMA overexpression as a biomarker for neoangiogenesis, in both oncological and infective disorders.

9.
Stem Cells Dev ; 29(9): 586-598, 2020 05 01.
Artigo em Inglês | MEDLINE | ID: mdl-32160799

RESUMO

Intracerebral hemorrhage (ICH) is as a life-threatening condition that can occur in young adults, often causing long-term disability. Recent preclinical data suggest mesenchymal stromal cell (MSC)-based therapies as promising options to minimize brain damage after ICH. However, therapeutic evidence and mechanistic insights are still limited, particularly when compared with other disorders such as ischemic stroke. Herein, we employed a model of collagenase-induced ICH in young adult rats to investigate the potential therapeutic effects of an intravenous injection of human umbilical cord Wharton's jelly-derived MSCs (hUC-MSCs). Two doses of collagenase were used to cause moderate or severe hemorrhages. Magnetic resonance imaging showed that animals treated with hUC-MSCs after moderate ICH had smaller residual hematoma volumes than vehicle-treated rats, whereas the cell therapy failed to decrease the hematoma volume in animals with a severe ICH. Functional assessments (rotarod and elevated body swing tests) were performed for up to 21 days after ICH. Enduring neurological impairments were seen only in animals subjected to severe ICH, but the cell therapy did not induce statistically significant improvements in the functional recovery. The biodistribution of Technetium-99m-labeled hUC-MSCs was also evaluated, showing that most cells were found in organs such as the spleen and lungs 24 h after transplantation. Nevertheless, it was possible to detect a weak signal in the brain, which was higher in the ipsilateral hemisphere of rats subjected to a severe ICH. These data indicate that hUC-MSCs have moderately beneficial effects in cases of less severe brain hemorrhages in rats by decreasing the residual hematoma volume, and that optimization of the therapy is still necessary.


Assuntos
Hemorragia Cerebral/terapia , Células-Tronco Mesenquimais/citologia , Cordão Umbilical/citologia , Animais , Encéfalo/citologia , Humanos , Masculino , Transplante de Células-Tronco Mesenquimais/métodos , Ratos , Recuperação de Função Fisiológica/fisiologia , Distribuição Tecidual/fisiologia , Geleia de Wharton/citologia
10.
Am J Trop Med Hyg ; 102(4): 797-799, 2020 04.
Artigo em Inglês | MEDLINE | ID: mdl-32043461

RESUMO

Chronic Chagas heart disease has different clinical manifestations including arrhythmias, heart failure, and stroke. Chest pain is one of the most common symptoms and when associated with changes in the electrocardiogram, such as T-wave changes, electrically inactive areas, and segmental wall motion abnormalities, may lead to a misdiagnosis of acute coronary syndrome (ACS). Here, we describe two patients with Chagas heart disease and syncope due to sustained ventricular tachycardia who were misdiagnosed with ACS, and discuss the role of novel imaging modalities in the differential diagnosis and risk stratification.


Assuntos
Arritmias Cardíacas/etiologia , Cardiomiopatia Chagásica/complicações , Idoso , Amiodarona/administração & dosagem , Amiodarona/uso terapêutico , Antiarrítmicos/administração & dosagem , Antiarrítmicos/uso terapêutico , Clopidogrel/administração & dosagem , Clopidogrel/uso terapêutico , Desfibriladores Implantáveis , Diagnóstico Diferencial , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Inibidores da Agregação Plaquetária/administração & dosagem , Inibidores da Agregação Plaquetária/uso terapêutico
11.
Medicine (Baltimore) ; 97(49): e13460, 2018 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-30544431

RESUMO

RATIONALE: Myasthenia gravis (MG) is an uncommon autoimmune disease mediated by antibodies that attack the postsynaptic acetylcholine receptors (AchRs) at the neuromuscular junction, causing fluctuating muscle weakness, aggravated with use, and relieved with rest. PATIENT CONCERNS: A 32-year-old woman with a diagnosis of MG based on clinical findings, eletroneuromyography, and brain magnetic resonance imaging (MRI) was admitted to our hospital with dysphagia, dysphonia, diplopia, and intense weakness, associated with a 2-day viral gastroenteritis. DIAGNOSES: Physical examination revealed globally reduced deep tendon reflexes, and tetraparesis, with muscle strength grade 4 in the left limbs and grade 2 in the right limbs. Autoantibody dosing against AchR was elevated and computed tomography scan of the thorax revealed a thymic remnant. INTERVENTIONS: Pyridostigmine and human immunoglobulin were infused. OUTCOMES: After 7 days of the reintroduction of pyridostigmine and human immunoglobulin infusion, the patient developed complete resolution of symptoms, being discharged from the hospital. Her symptoms are still well controlled 6 months later. The patient was evaluated by a thoracic surgeon and is awaiting elective thymectomy. LESSONS: Although our patient presented all the diagnostic criteria of MG, the markedly asymmetric limb weakness presented in previous history and clinical examination of admission was an unusual and unexpected presentation, especially considering the pathophysiology of the disease. MRI of brain without abnormalities was fundamental to rule out another associated etiology. Our review of the literature revealed just 1 case report of MG with similar presentation. This clinical manifestation becomes valuable because it contributes to the list of unexpected presentation that should motivate its suspicion.


Assuntos
Miastenia Gravis/diagnóstico , Miastenia Gravis/terapia , Adulto , Diagnóstico Diferencial , Feminino , Humanos
12.
Biomed Res Int ; 2018: 5208964, 2018.
Artigo em Inglês | MEDLINE | ID: mdl-30356372

RESUMO

Molecular imaging of estrogen receptor-positive (ER+) pathway-activated system serves the basis of ER+ disease management such as cancers and endometriosis. ER+ patients have better response to endocrine therapy and survive twice as long as negative ER patients. However, tumor resistance resulting from clinical used aromatase inhibitors and antiestrogens is unpredictable. Radiolabeled ER+ ligand could quantify ER+ tissue uptake which helps to stage and restage of the cancer as well as endometriosis. The differential diagnosis of ER+ lesions by using a labeled ligand helps to select the patients for optimal response to endocrine therapy and to discontinue the treatment when resistance occurs. In addition, radiolabeled ER+ ligand serves as basis for image-guided response follow-up. Glutamate receptors are cell surface receptors which are overexpressed in inflammation and infection. Using glutamate peptide as a drug carrier helps to target intracellular genes via glutamate receptor-mediated process. Reports have shown that polyglutamate is a drug carrier that could alter drug solubility and enhance estrogen receptor-ligand binding pocket. However, polyglutamate was a blend of mixed polymer with a wide range of molecular weight. Thus, the structural confirmation and purity of the conjugates were not optimized. To overcome this problem, the efficient synthesis of glutamate peptide-estradiol (GAP-EDL) conjugate was achieved with high purity. EDL was conjugated site-specific at the first glutamate of GAP. The average cell uptake of 68Ga-GAP-EDL was 5-fold higher than the previous reported synthesis. The efficient synthesis of GAP-EDL has greatly enhanced sensitivity and specificity in cell uptake studies. In vivo PET imaging studies indicated that 68Ga-GAP-EDL could image ER (+) tumors in MCF-7 tumor-bearing mice. Therefore, GAP-EDL makes it possible to image ER-enriched endometriosis and cancer.


Assuntos
Neoplasias da Mama/diagnóstico por imagem , Estradiol , Radioisótopos de Gálio , Marcação por Isótopo , Peptídeos , Tomografia por Emissão de Pósitrons , Neoplasias da Mama/metabolismo , Estradiol/síntese química , Estradiol/química , Estradiol/farmacologia , Feminino , Radioisótopos de Gálio/química , Radioisótopos de Gálio/farmacologia , Humanos , Células MCF-7 , Peptídeos/síntese química , Peptídeos/química , Peptídeos/farmacologia
14.
Int J Nanomedicine ; 12: 779-793, 2017.
Artigo em Inglês | MEDLINE | ID: mdl-28182122

RESUMO

Superparamagnetic iron oxide nanoparticles (SPIONs) have been used for diagnoses in biomedical applications, due to their unique properties and their apparent safety for humans. In general, SPIONs do not seem to produce cell damage, although their long-term in vivo effects continue to be investigated. The possibility of efficiently labeling cells with these magnetic nanoparticles has stimulated their use to noninvasively track cells by magnetic resonance imaging after transplantation. SPIONs are attracting increasing attention and are one of the preferred methods for cell labeling and tracking in preclinical and clinical studies. For clinical protocol approval of magnetic-labeled cell tracking, it is essential to expand our knowledge of the time course of SPIONs after cell incorporation and transplantation. This review focuses on the recent advances in tracking SPION-labeled stem cells, analyzing the possibilities and limitations of their use, not only focusing on myocardial infarction but also discussing other models.


Assuntos
Rastreamento de Células/métodos , Imageamento por Ressonância Magnética/métodos , Nanopartículas de Magnetita/química , Células-Tronco/química , Células-Tronco/citologia , Animais , Humanos
15.
Stem Cells Int ; 2016: 4617983, 2016.
Artigo em Inglês | MEDLINE | ID: mdl-27698671

RESUMO

Stroke is the second leading cause of mortality worldwide, causing millions of deaths annually, and is also a major cause of disability-adjusted life years. Hemorrhagic stroke accounts for approximately 10 to 27% of all cases and has a fatality rate of about 50% in the first 30 days, with limited treatment possibilities. In the past two decades, the therapeutic potential of bone marrow-derived cells (particularly mesenchymal stem cells and mononuclear cells) has been intensively investigated in preclinical models of different neurological diseases, including models of intracerebral hemorrhage and subarachnoid hemorrhage. More recently, clinical studies, most of them small, unblinded, and nonrandomized, have suggested that the therapy with bone marrow-derived cells is safe and feasible in patients with ischemic or hemorrhagic stroke. This review discusses the available evidence on the use of bone marrow-derived cells to treat hemorrhagic strokes. Distinctive properties of animal studies are analyzed, including study design, cell dose, administration route, therapeutic time window, and possible mechanisms of action. Furthermore, clinical trials are also reviewed and discussed, with the objective of improving future studies in the field.

16.
Stem Cells Int ; 2016: 8657173, 2016.
Artigo em Inglês | MEDLINE | ID: mdl-27525011

RESUMO

Background and Purpose. BM-MNC transplantation improves recovery in experimental models of ischemic stroke. Clinical trials are ongoing to test efficacy in stroke patients. However, whether cell dose is related to outcomes is not known. Methods. We performed a pooling data analysis of two pilot clinical trials with autologous BM-MNCs transplantation in ischemic stroke patients. Cell dose and route were analyzed to evaluate their relation to good outcome (m-Rankin scale [mRS] score 0-2) at 6 months. Results. Twenty-two patients were included. A median of 153 × 10(6) (±121 × 10(6)) BM-MNCs was injected. Intra-arterial route was used in 77.3% of cases. A higher number of cells injected were associated with better outcomes at 180 days (390 × 10(6) [320-422] BM-MNCs injected in those patients with mRS of 0-2 at 6 months versus 130 × 10(6) [89-210] in those patients with mRS 3-6, p = 0.015). In the intra-arterially treated patients, a strong correlation between dose of cells and disability was found (r = -0.63, p = 0.006). A cut point of 310 × 10(6) injected cells predicted good outcome with 80% sensitivity and 88.2% specificity. Conclusions. Similar to preclinical studies, a higher dose of autologous BM-MNC was related to better outcome in stroke patients, especially when more than 310 × 10(6) cells are injected. Further interventional studies are warranted to confirm these data.

17.
Clin Nucl Med ; 40(2): 123-7, 2015 02.
Artigo em Inglês | MEDLINE | ID: mdl-25546220

RESUMO

BACKGROUND: Medullary thyroid cancer (MTC) is a rare but potentially life-threatening disease with limited therapeutic options. As a neuroendocrine tumor, MTC expresses somatostatin receptors, and therefore, somatostatin-labeled radiopharmaceuticals could be used to treat patients with MTC. OBJECTIVE: The aims of this study were to evaluate tumor shrinkage after Lu-DOTATATE treatment, to analyze the impact on quality of life as accessed by the SF-36 questionnaire, and to demonstrate a possible prognostic role for In-DTPA-octreotide uptake in patients with MTC. PATIENTS AND METHODS: Patients with progressive MTC underwent evaluation using In-DTPA-octreotide. Patients who demonstrated In-DTPA-octreotide uptake were treated with 4 cycles of 200 mCi of Lu-DOTATATE and were evaluated using CT scans over 8 to 12 months of treatment. RESULTS: Of the 16 patients initially enrolled, 9 (56.25%) had lesions that were observed in the In-DTPA-octreotide scans and were eligible for therapy with Lu-DOTATATE. Three patients had a partial response, 3 patients were classified as having stable disease and, 1 patient had a progressive disease. All responders indicated improvement in quality of life 6 to 12 months after therapy. CONCLUSIONS: Treatment with Lu-DOTATATE seems to be an alternative therapy for somatostatin receptor-positive tumors, with very mild adverse effects and quality-of-life improvement, at least during a short-term period. Further studies are needed to determine long-term benefits and to identify which patients are more likely to respond to this modality of therapy.


Assuntos
Octreotida/análogos & derivados , Compostos Organometálicos/uso terapêutico , Compostos Radiofarmacêuticos/uso terapêutico , Neoplasias da Glândula Tireoide/radioterapia , Adulto , Idoso , Carcinoma Neuroendócrino , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Octreotida/uso terapêutico , Ácido Pentético/análogos & derivados , Qualidade de Vida , Tomografia Computadorizada por Raios X
18.
Biomed Res Int ; 2014: 417091, 2014.
Artigo em Inglês | MEDLINE | ID: mdl-24982880

RESUMO

Although neurological ailments continue to be some of the main causes of disease burden in the world, current therapies such as pharmacological agents have limited potential in the restoration of neural functions. Cell therapies, firstly applied to treat different hematological diseases, are now being investigated in preclinical and clinical studies for neurological illnesses. However, the potential applications and mechanisms for such treatments are still poorly comprehended and are the focus of permanent research. In this setting, noninvasive in vivo imaging allows better understanding of several aspects of stem cell therapies. Amongst the various methods available, radioisotope cell labeling has become one of the most promising since it permits tracking of cells after injection by different routes to investigate their biodistribution. A significant increase in the number of studies utilizing this method has occurred in the last years. Here, we review the different radiopharmaceuticals, imaging techniques, and findings of the preclinical and clinical reports published up to now. Moreover, we discuss the limitations and future applications of radioisotope cell labeling in the field of cell transplantation for neurological diseases.


Assuntos
Rastreamento de Células/métodos , Doenças do Sistema Nervoso/diagnóstico por imagem , Doenças do Sistema Nervoso/patologia , Compostos Radiofarmacêuticos , Células-Tronco/diagnóstico por imagem , Animais , Ensaios Clínicos como Assunto , Humanos , Cintilografia , Coloração e Rotulagem
19.
Brain Res ; 1522: 1-11, 2013 Jul 19.
Artigo em Inglês | MEDLINE | ID: mdl-23721927

RESUMO

Global cerebral ischemia (GCI) results in death of the pyramidal neurons in the CA1 layer of the hippocampus. In this study we used the four-vessel occlusion (4VO) model of GCI to investigate a potential neuroprotective role of bone-marrow mononuclear cells (BMMCs) transplantation. BMMCs (3×10(7)) were injected through the carotid artery, 1 or 3 days after ischemia (DAI), and the number of cells undergoing degeneration was investigated in brains at 7 DAI. A significant decrease in the number of dying cells was observed in the treated group, compared to animals treated with saline. Biodistribution of the injected cells (1 or 3 DAI) was investigated by (99m)Technetium labeling of the BMMCs and subsequent image analysis 2h after transplantation. In addition, the presence of CellTrace(™)-labeled BMMCs was investigated in tissue sections of the hippocampal area of these transplanted animals. BMMCs treatment significantly reduced the number of FJ-C positive cells in the hippocampal CA1 layer at 7 DAI. We also observed a decrease in the number of activated microglia/macrophage (ED1-positive cells) in the BMMCs-treated group compared with the untreated group. Our data show that BMMCs are able to modulate the microglial response and reduce neurodegeneration in the CA1 layer.


Assuntos
Transplante de Medula Óssea/métodos , Isquemia Encefálica/patologia , Região CA1 Hipocampal/patologia , Leucócitos Mononucleares/transplante , Degeneração Neural/patologia , Animais , Células da Medula Óssea , Masculino , Ratos , Ratos Wistar
20.
Clinics (Sao Paulo) ; 68(3): 283-9, 2013.
Artigo em Inglês | MEDLINE | ID: mdl-23644845

RESUMO

OBJECTIVE: Mammography has been established as the gold standard for the detection of breast cancer, and imaging techniques such as ultrasonography, magnetic resonance imaging, scintigraphy and positron emission tomography may be useful to improve its sensitivity and specificity. The objective of this study with breast scintigraphy was to evaluate the uptake of 99mTc-thymine in mammary lesions. METHODS: A total of 45 patients were included in this study. Thirty-three patients (73%) were subjected to surgery or percutaneous biopsy, providing histopathological data. The other 12 patients who remained under surveillance received clinical examinations and biannual mammography with a normal follow-up of at least three years, the data from which were used for comparison with the scintimammography results. RESULTS: The majority of patients (64.4%) had clinically impalpable lesions with a mammogram diagnosis of microcalcifications, impalpable nodules, or focal asymmetry. Of the studied lesions, 87% were smaller or equal to 20 mm in diameter, and 22% had malignant histopathological findings. Scintigraphy with 99mTc-thymine had a sensitivity of 70%, a specificity of 85.7%, positive and negative predictive values of 58.3% and 90.9%, respectively, and an accuracy of 82.2%. CONCLUSIONS: The results of this study are consistent with those previously reported by other authors. The good specificity and high negative predictive value of this technique and the absence of uptake in the heart indicate that it may be a promising complementary method in clinical practice and that it may contribute to reducing unnecessary benign biopsies.


Assuntos
Neoplasias da Mama/diagnóstico por imagem , Mamografia/métodos , Compostos de Organotecnécio , Compostos Radiofarmacêuticos , Timina/análogos & derivados , Adulto , Idoso , Idoso de 80 Anos ou mais , Biópsia , Neoplasias da Mama/patologia , Feminino , Humanos , Pessoa de Meia-Idade , Valor Preditivo dos Testes , Cintilografia , Reprodutibilidade dos Testes
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