Evidencing leprosy neuronal inflammation by 18-Fluoro-deoxy-glucose.

BACKGROUND: Leprosy is caused by multiple interactions between Mycobacterium leprae (M. leprae) and the host's peripheral nerve cells. M. leprae primarily invades Schwann cells, causing nerve damage and consequent development of disabilities. Despite its long history, the pathophysiological mechanisms of nerve damage in the lepromatous pole of leprosy remain poorly understood. This study used the findings of 18F-FDG PET/CT on the peripheral nerves of eight lepromatous patients to evaluate the degree of glucose uptake by peripheral nerves and compared them with clinical, electrophysiological, and histopathological evaluations. METHODS: Eight patients with lepromatous leprosy were included in this study. Six patients were evaluated up to three months after leprosy diagnosis using neurological examination, nerve conduction study, 18F-FDG PET/CT, and nerve biopsy. Two others were evaluated during an episode of acute neuritis, with clinical, neurophysiological, and PET-CT examinations to compare the images with the first six. RESULTS: Initially, six patients already had signs of peripheral nerve injury, regardless of symptoms; however, they did not present with signs of neuritis, and there was little or no uptake of 18F-FDG in the clinically and electrophysiologically affected nerves. Two patients with signs of acute neuritis had 18F-FDG uptake in the affected nerves. CONCLUSIONS: 18F-FDG uptake correlates with clinical neuritis in lepromatous leprosy patients but not in silent neuritis patients. 18F-FDG PET-CT could be a useful tool to confirm neuritis, especially in cases that are difficult to diagnose, such as for the differential diagnosis between a new episode of neuritis and chronic neuropathy.

The Use of 99mTc-Mononuclear Leukocyte Scintigraphy for Necrotizing External Otitis Diagnosis.

BACKGROUND: Necrotizing external otitis (NEO) is a severe infectious disease in the external acoustic meatus (EAM) and mastoid that may extend to the cranial base. Due to the lack of a gold standard examination technique, the diagnosis is often difficult and delayed. This study aimed to evaluate the sensitivity and specificity of 99mTc-mononuclear leukocyte scintigraphy associated with 99mTc-phytate in suspected NEO compared to 99mTc-MDP and 67Ga-citrate. METHODS: A prospective study (32 patients) was conducted between 2011 and 2016. RESULTS: At the end, twenty-four patients remained for the study conduction; nineteen had confirmed NEO diagnosis, one had sarcoma, one had EAM cholesteatoma, one had diffuse simple external otitis, and two had an inconclusive diagnosis. 99mTc-mononuclear leukocyte scintigraphy plus 99mTc-phytate was as sensitive as 99mTc-MDP bone scintigraphy (19/19X9/19), and more sensitive than 67Ga scintigraphy (19/19 x 17/19). Regarding specificity, it was superior to bone scintigraphy, 100% × 40% (5/5 × 2/5), and 67Ga scintigraphy, 100% × 20% (5/5 × 1/5). After the infection resolution, all NEO patients had their leukocyte scintigraphy negativized. To the best of our knowledge, this is the first study that evaluates this technique in patients with suspected NEO. CONCLUSIONS: 99mTc-mononuclear leukocyte was revealed to be the best option for NEO because of its specificity.

Rat thyroid graft transplantation after cryopreservation with scintigraphic standardization for an experimental study.

PURPOSE: Budget cuts among other factors undermine the use of state-of-the-art equipment by many research groups. This doesn't mean that their scientific data are not reliable or top-notch. Resort to adaptations is a recurrent need in their reality. The aim of this study was to assess whether scintigraphy with 99mTcO4 is effective in evaluating the functionality of thyroid grafts after cryopreservation in rats. MATERIAL AND METHODS: 24 rats were randomly distributed into 3 groups: Control Group (CG), without surgical procedure, Hypothyroidism Group (HTG), submitted to total thyroidectomy, and Transplanted Group (TG), with total thyroidectomy and cryopreservation of the thyroid gland for 7 days followed by grafting of a thyroid lobe. A protocol using a gamma camera imaging was conducted fourteen weeks after transplantation, and the whole body 99mTc, focusing on the topic of heterotopic thyroid uptake was evaluated. RESULTS: The images acquired had good quality with no noise and artifacts that could jeopardize its analysis. On the 14th day, HTG displayed no thyroid uptake, and the TG had a clear uptake of the thyroid graft in the topography of the biceps femoris muscle. Presented data also showed that both equipment spatial resolution and alignment (4.375 mm) did not interfere with the physiological uptake of 99mTc by the thyroid graft. CONCLUSION: The viability and functionality of cryopreserved thyroid autotransplantation in rats who underwent total thyroidectomy were successfully accessed by the scintigraphy protocol developed.

Development of 131I-ixolaris as a theranostic agent: metastatic melanoma preclinical studies.

Tissue factor (TF), a blood coagulation protein, plays an important role in tumor growth, invasion, and metastasis. Ixolaris, a tick-derived non-immunogenic molecule that binds to TF, has demonstrated in vivo inhibitory effect on murine models of melanoma, including primary growth and metastasis. This work aimed to: I) develop an efficient and stable labeling technique of ixolaris with Iodine-131(131I); II) compare the biodistribution of 131I and 131I-ixolaris in tumor-free and melanoma-bearing mice; III) evaluate whether 131I-ixolaris could serve as an antimetastatic agent. Ixolaris radioiodination was performed using iodogen, followed by liquid paper chromatography. Labeling stability and anticoagulant activity were measured. Imaging studies were performed after intravenous administration of free 131I or 131I-ixolaris in a murine melanoma model employing the B16-F10 cell line. Animals were divided in three experimental groups: the first experimental group, D0, received a single-dose of 9.25 MBq of 131I-ixolaris at the same day the animals were inoculated with melanoma cells. In the second group, D15, a single-dose of 9.25 MBq of 131I-ixolaris or free 131I was applied into mice on the fifteenth day after the tumor induction. The third group, D1-D15, received two therapeutic doses of 9.25 MBq of 131I-ixolaris or 131I. In vitro studies demonstrated that 131I-ixolaris is stable for up to 24 h and retains its inhibitory activity on blood coagulation. Biodistribution analysis and metastasis assays showed that all treatment regimens with 131I-ixolaris were effective, being the double-treatment (D1/D15) the most effective one. Remarkably, treatment with free 131I showed no anti-metastatic effect. 131I-ixolaris is a promising theranostic agent for metastatic melanoma.

Safety and Localization of Mesenchymal Stromal Cells Derived from Human Adipose Tissue-Associated Hyaluronic Acid: A Preclinical Study.

Millions of plastic surgeries are performed worldwide every year with the objective of correcting lipodystrophies stemming from lesions, tumor resections, birth defects, and AIDS-associated antiretroviral therapy. Besides that, a large number of clinical research have assessed the outcome of procedures that rely on combinations of dermal fillers and autologous cells. However, little is known about the safety of these combinations and the localization of the injected cells. The aim of this study was to test the toxicity of a solution containing 1% hyaluronic acid (HA) and adipose-derived stromal cells (ASCs) from the human adipose tissue and to assess the localization of the injected cells, with and without HA, labeled with technetium-99m. Rats received subcutaneous and intraperitoneal injections of a solution containing 1% HA/adipose-derived stromal cells isolated from the human fat tissue. The animals were then observed for up to forty-two days. The solution tested in this study did not result in systemic, biochemical, or anatomic alterations that could represent toxicity symptoms. The association of HA and ASCs labeled with technetium-99m remained at the site of the injection within a period of twenty-four hours, as demonstrated by a whole-body imaging software fusion of SPECT and CT. In conclusion, our study shows that the subcutaneous and intraperitoneal injection of HA associated with adipose-derived stromal cells (ASCs) is safe. The association of HA and ASCs did not induce local or systemic toxicity. Thus, the administration of volume equal to or less than 0.2 mL of the agent filler (1 × 106 ASC+HA 1%) should be considered for subsequent studies and may be an alternative to dermal fillers due to the expected lasting effects.

Outpatient treatment for haemophilic arthropathy with radiosynovectomy: Radiation dose to family members.

One of the key features of good practice in medicine is the doctor-patient communication. Radiation protection standards for radiosynovectomy (RS) is limited. Yttrium-90 is a beta-emitting radioisotope used in RS to treat joint pain from haemophilic arthritis. ICRP 94 states that if a patient is treated with up to 200 MBq, there is no need for further precautions when it comes to public exposure, however, activities can go up to 370 MBq in RS for the knee. This study analysed 119 family members' safety (16.7% pregnant women). The ambient dose equivalent rate was measured within four distances. A survey was carried analysing risk groups and time spent next to patients. Results showed that family members should be advised to remain at 1.0 m from the patient to decrease accumulated dose by 97.6%. The dose per activity factors estimated in this study is also a useful tool during the risk assessment and doctor/patient communication. Pamphlets were distributed with radiation protection recommendations. Ambient dose equivalent was low enough to show that RS is a safe procedure for family members, which is essential to promote adherence to RS in countries where it is needed but not performed due to lack of information on radiation safety.

Qualitative and quantitative scintigraphy in sialorrhea before and after botulinum toxin injection.

OBJECTIVES/HYPOTHESIS: Sialorrhea is excessive saliva production and its usual escape of from the oral cavity. The use of botulinum toxin has been preconized, but its effectiveness until now has been unreliably measured. Our objective was to qualitatively and quantitatively determine the effectiveness of botulinum toxin injection in the reduction of saliva production by the parotid gland. STUDY DESIGN: Outcomes research. METHODS: Patients with moderate-to-critical sialorrhea had one of the parotid glands injected with 50 U of botulinum toxin, leaving the other as the control. Fifteen days after the toxin injection, they underwent scintigraphic analyses with intravenous injection of 10 mCi (37 MBq) of Tc-99 m (sodium pertechnetate). After this, the noninjected gland was treated for therapeutic complementation. RESULTS: The glands injected with botulinum toxin showed uptake reduction in 100% of patients. The uptake reduction in counts per second varied from 8% to 36%. The Wilcoxon paired test comparing the control glands with those injected showed a significant difference for the action of botulinum toxin (P = .0039). CONCLUSIONS: The scintigraphic study of parotid glands shows that botulinum toxin is effective in reducing sodium pertechnetate uptake. LEVEL OF EVIDENCE: 2c Laryngoscope, 129:2521-2526, 2019.

Technetium-99m-anti-tumour necrosis factor alpha scintigraphy as promising predictor of response to corticotherapy in chronic active Graves' ophthalmopathy.

It has been suggested that technetium-99m (99mTc)-anti-tumour necrosis factor alpha (TNF-α) scintigraphy (SCI) may be a useful diagnostic tool in Graves' ophthalmopathy (GO). This study evaluated whether orbit total radioactivity uptake on SCI could be used to predict corticosteroid therapy (CorT) responses in active-GO patients. A longitudinal study of patients with active GO defined by Clinical Active Score (CAS) >3/7 was done. Clinical, laboratory and SCI evaluations were performed at baseline and 3 months after concluding intravenous CorT. SCI (planar and tomographic) was assessed after intravenous injection of 10 mCi of 99mTc-anti-TNF-α. Orbits and cerebral hemispheres were defined as regions of interest (ROIs) to enable orbit/hemisphere ROI-ratios of total radioactive uptake. ROI-ratios were considered positive at >2·5. Average total radiation uptake (TRU) was also determined for each orbit (AVGROI ). Clinical, laboratory and SCI data were compared between responders (CAS became inactive) and non-responders to CorT (18 patients). At baseline, AVGROI were higher in active OG orbits (67·3 cps) than in inactive ones (33·6 cps; P<0·05). AVGROI (absolute values) reduced (-29·9 cps) in CorT responders and tended (P = 0·067) to differ from variations occurred in non-responders (+6·9 cps in patients with maintained CAS positivity post-treatment). Higher baseline ROI-ratios (4·9 versus 3·3; P = 0·056) and its pronounced reductions following CorT (-37% versus +56% in non-responders; P = 0·036) tended to be associated with good CorT responses in the subgroup of GO history ≥1 year. SCI showed a good association with active eye disease and may be an additional tool to identify CorT responders.

EXPLORING CORTICAL BONE DENSITY THROUGH THE ULTRASOUND INTEGRATED REFLECTION COEFFICIENT.

OBJECTIVE: This work evaluates the relationship between ultrasonic reflection and bone density from fourteen cylindrical bovine cortical bone samples (3.0-cm thick). METHODS: Twenty US reflection signals per sample were acquired along the bone surface (2.0-mm step). The Integrated Reflection Coefficient (IRC) from each signal was compared to Quantitative Computed Tomography (QCT). RESULTS: Seven IRC and QCT curves presented Pearson's Correlation R-values above 0.5. For weak correlation curves, QCT and IRC showed similar trends in several segments. CONCLUSION: IRC was sensitive to bone density variation. Level of Evidence: Experimental Study, Investigating a Diagnostic Test.

OBJETIVO: Este estudo avalia a relação entre a reflexão ultrassônica e a densidade óssea de 14 amostras cilíndricas de osso cortical bovino (3,0 cm de espessura). MÉTODOS: Foi realizada a aquisição de 20 sinais de reflexão ultrassônica por amostra (passo de 2,0 mm), ao longo da superfície óssea. O Coeficiente de Reflexão Integrado (IRC) de cada sinal foi comparado por Tomografia Computadorizada Quantitativa (QCT). RESULTADOS: Sete curvas de IRC e QCT apresentaram valor de Correlação R de Pearson acima de 0,5. Para curvas de correlação fraca, QCT e IRC apresentaram tendências semelhantes em vários segmentos. CONCLUSÃO: O IRC foi sensível à variação da densidade óssea. Nível de evidência: Estudo Experimental, Investigação de Exame Diagnóstico.

Dietary supplementation with hybrid palm oil alters liver function in the common Marmoset.

Hybrid palm oil, which contains higher levels of oleic acid and lower saturated fatty acids in comparison with African palm oil, has been proposed to be somehow equivalent to extra virgin olive oil. However, the biological effects of its consumption are poorly described. Here we have explored the effects of its overconsumption on lipid metabolism in a non-human primate model, the common marmoset. Dietary supplementation of marmoset with hyperlipidic diet containing hybrid palm oil for 3 months did not modify plasma lipids levels, but increased glucose levels as compared to the supplementation with African palm oil. Liver volume was unexpectedly found to be more increased in marmosets consuming hybrid palm oil than in those consuming African palm oil. Hepatic total lipid content and circulating transaminases were dramatically increased in animals consuming hybrid palm oil, as well as an increased degree of fibrosis. Analysis of liver miRNAs showed a selective modulation of certain miRNAs by hybrid palm oil, some of which were predicted to target genes involved in cell adhesion molecules and peroxisomal pathways. Our data suggest that consumption of hybrid palm oil should be monitored carefully, as its overconsumption compared to that of African palm oil could involve important alterations to hepatic metabolism.

Therapeutic effects of bone marrow-derived mononuclear cells from healthy or silicotic donors on recipient silicosis mice.

BACKGROUND: Administration of bone marrow mononuclear cells (BMMCs) modulates lung inflammation and fibrosis in experimental silicosis. However, no studies have evaluated whether silicosis affects the efficacy of autologous BMMCs treatment. We hypothesized that BMMCs obtained from healthy or silicotic mice may improve lung function, but they might affect the inflammatory and fibrotic processes differently in experimental silicosis. METHODS: C57BL/6 mice were randomly divided into control (C) and silicosis (SIL) groups. Mice in the SIL group were instilled with silica particles intratracheally; the C animals received saline using the same protocol. On day 15, the animals were treated with saline (Sal) or BMMCs (2 × 106 cells) from healthy (BMMC-healthy) and silicotic (BMMC-sil) donors. Lung mechanics were measured, and lungs were collected for histology and molecular biology analysis. RESULTS: BMMCs obtained from healthy and silicotic donors presented similar percentages of cell populations. 99mTc-BMMCs tracking revealed preferential migration of cells to the liver, and only a few GFP+ BMMCs were observed in lung tissue 24 h after treatment, regardless of donor type. Both the SIL-BMMC-healthy and SIL-BMMC-sil groups showed improvement in lung function, a reduction in the fractional area of granuloma, and a decrease in the number of mononuclear and apoptotic cells in lung parenchyma. In addition, the number of F4/80+ macrophages, the levels of interleukin-1 beta and transforming growth factor beta, and collagen fiber content in granuloma were reduced in SIL-BMMC-healthy mice, whereas mRNA expression of MMP-9 and procollagen I and III was reduced in the SIL-BMMC-sil group. CONCLUSIONS: Administration of BMMCs from healthy and silicotic donors reduced lung inflammation and fibrosis, thus improving lung function. In addition, BMMC-healthy exhibited a greater improvement in lung morpho-functional changes in murine model of silicosis.

In Vivo Tracking of Cell Therapies for Cardiac Diseases with Nuclear Medicine.

Even though heart diseases are amongst the main causes of mortality and morbidity in the world, existing treatments are limited in restoring cardiac lesions. Cell transplantations, originally developed for the treatment of hematologic ailments, are presently being explored in preclinical and clinical trials for cardiac diseases. Nonetheless, little is known about the possible efficacy and mechanisms for these therapies and they are the center of continuous investigation. In this scenario, noninvasive imaging techniques lead to greater comprehension of cell therapies. Radiopharmaceutical cell labeling, firstly developed to track leukocytes, has been used successfully to evaluate the migration of cell therapies for myocardial diseases. A substantial rise in the amount of reports employing this methodology has taken place in the previous years. We will review the diverse radiopharmaceuticals, imaging modalities, and results of experimental and clinical studies published until now. Also, we report on current limitations and potential advances of radiopharmaceutical labeling for cell therapies in cardiac diseases.

99m-Technetium binding site in bone marrow mononuclear cells.

INTRODUCTION: The increasing interest in 99m-technetium ((99m)Tc)-labeled stem cells encouraged us to study the (99m)Tc binding sites in stem cell compartments. METHODS: Bone marrow mononuclear cells were collected from femurs and tibia of rats. Cells were labeled with (99m)Tc by a direct method, in which reduced molecules react with (99m)Tc with the use of chelating agents, and lysed carefully in an ultrasonic apparatus. The organelles were separated by means of differential centrifugation. At the end of this procedure, supernatants and pellets were counted, and the percentages of radioactivity (in megabecquerels) bound to the different cellular fractions were determined. Percentages were calculated by dividing the radioactivity in each fraction by total radioactivity in the sample. The pellets were separated and characterized by their morphology on electron microscopy. RESULTS: The labeling procedure did not affect viability of bone marrow mononuclear cells. Radioactivity distributions in bone marrow mononuclear cell organelles, obtained in five independent experiments, were approximately 38.5 % in the nuclei-rich fraction, 5.3 % in the mitochondria-rich fraction, 2.2 % in microsomes, and 54 % in the cytosol. Our results showed that most of the radioactivity remained in the cytosol; therefore, this is an intracellular labeling procedure that has ribosomes unbound to membrane and soluble molecules as targets. However, approximately 39 % of the radioactivity remained bound to the nuclei-rich fraction. To confirm that cell disruption and organelle separation were efficient, transmission electron microscopy assays of all pellets were performed. CONCLUSIONS: Our results showed that most of the radioactivity was present in the cytosol fraction. More studies to elucidate the mechanisms involved in the cellular uptake of (99m)Tc in bone marrow cells are ongoing.

Use of (99m)Tc-anti-TNF-α scintigraphy in a patient with non-radiographic axial spondyloarthritis.

The aim of this study was to describe the use of (99m)Tc-anti-TNF-α scintigraphy for detecting inflammation of the sacroiliac joints in a patient with non-radiographic axial spondyloarthritis. A 47-year-old female patient, non-smoker and non-drinker, complained of a low back pain inflammation, which began 4 years before her condition have exacerbated to morning stiffness and anterior uveitis in the last 6 months. Initially diagnosed as mechanical low back pain, she irregularly took non-steroidal anti-inflammatory drugs and corticosteroids, without significant long-lasting results. Radiographic findings were negative. There was increased uptake of (99m)Tc-anti-TNF-α in an area corresponding to the topography of ileum and sacroiliac right joint upon (99m)Tc-anti-TNF-α scintigraphy. Magnetic resonance imaging (MRI), the most used image diagnosis tool, showed minimum impregnation of gadolinium in the right sacroiliac joint and at the iliac face of the inferior third of the right sacroiliac joint. We suggest that (99m)Tc-anti-TNF-α can facilitate early diagnosis of patients with non-radiographic axial spondyloarthritis. More studies are now ongoing.

99mTc-Anti-TNF-α scintigraphy: a new perspective within different methods in the diagnostic approach of active Graves ophthalmopathy.

Different imaging methods applied in the evaluation of a patient with unilateral active Graves ophthalmopathy (GO) are shown in the present paper. 99mTc-Anti-TNF-α scintigraphy is proposed as a promising method, not yet described, for the diagnosis of active ocular disease. It consists of labeling a human monoclonal antibody directed against TNF-α molecule (adalimumab) with technetium (99mTc). The method is based on the demonstration of TNF-α as one of the cytokines enrolled in the initial active phase of GO development. The method may give the perspective to link diagnosis and therapy, including new target-based modalities.

Iodine-123 metaiodobenzylguanidine cardiac imaging as a method to detect early sympathetic neuronal dysfunction in chagasic patients with normal or borderline electrocardiogram and preserved ventricular function.

PURPOSE: The indeterminate form of Chagas disease represents the most common chronic presentation. The aim of this study was to assess cardiovascular autonomic system function with I-123 metaiodobenzylguanidine (MIBG) scintigraphy in chagasic patients with normal or "borderline" electrocardiographic alterations and preserved left ventricular function evaluated by echocardiography. MATERIALS AND METHODS: A total of 40 chagasic patients and 19 control subjects were included in this study. Patients had normal echocardiogram and chest radiography; no arrhythmias or myocardial ischemia; and normal exercise performance for age, gender, and body mass index. I-123 MIBG scintigraphy was performed and the heart-to-mediastinum (H/M) uptake was used as the primary predictor in the present analysis. The data analysis was performed by using Nonparametric Regression Trees and the Survival Agreement Plot. We included only patients with preserved right and left ventricular function assessed by echocardiographic methods. RESULTS: Variables analyzed in the regression tree were age, sex, 20 minutes and 3 hours H/M uptake after injection of I-123 MIBG, washout rate, and single photon emission computed tomography imaging. The 3 hours H/M ratio was the only significant variable (P<0.001) and for 95% of chagasic patients, this value was less than 2.19. CONCLUSIONS: This study presents evidence that cardiac autonomic sympathetic modulation may be affected in chagasic subjects with preserved ventricular function evaluated by echocardiography, especially in those with "borderline" electrocardiogram.

Radiolabeling of cramoll 1,4: evaluation of the biodistribution.

The cramoll 1,4 is a well-studied lectin. However, few studies about its biodistribution have been done before. In this study, we radiolabeled the cramol 1,4 with Tc-99m and analyzed the biodistribution. The results showed that the cramol has an abnormal uptake by the bowel with reflections on its clearance mechanism.

Use of 99mTc-anti-CD3 scintigraphy in the differential diagnosis of rheumatic diseases.

OBJECTIVES: The aim of this study was to assess the use of anti-CD3, labelled with technetium-99m scintigraphy, for evaluating the joints of patients with RA, juvenile idiopathic arthritis (JIA), OA and gouty arthritis, and to establish the diagnosis parameters for each disease. METHODS: We evaluated 2044 joints from 77 patients with rheumatic diseases. The clinical evaluation consisted of laboratory assays; examination for joint inflammation (pain and/or oedema); and for patients with RA, the disease activity score of 28 joints. To evaluate the sensitivity and specificity of 99mTc-anti-CD3 in detecting disease activity, patients received an injection of the radiopharmaceutical compound 99mTc-anti-CD3, and underwent a scintigraphy scan 1 h later. Scanning was repeated 3 h later. As a control, after 2 days, the patient was injected with 99mTc-non-specific human immunoglobulins, and scintigraphy scanning performed at 1 and 3 h after the injection. The intensity of uptake and the pattern of activity were defined, and Spearman's correlation and analysis of variance used for statistical evaluation. RESULTS: Diagnosis criteria were established for 99mTc-anti-CD3 uptake in different diseases. RA and JIA showed joint uptake with progressive increase in late images. Gouty arthritis showed joint uptake with decrease during the late images. Joint uptake was low or absent in patients with OA, although when present the joint uptake decreased during the examination. CONCLUSION: 99mTc-anti-CD3 scintigraphy is a useful method in the differential diagnosis of rheumatic diseases.