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.

The rise of cell therapy trials for stroke: review of published and registered studies.

Stroke is the second leading cause of death and the third leading cause of disability worldwide. Approximately 16 million first-ever strokes occur each year, leading to nearly 6 million deaths. Nevertheless, currently, very few therapeutic options are available. Cell therapies have been applied successfully in different hematological diseases, and are currently being investigated for treating ischemic heart disease, with promising results. Recent preclinical studies have indicated that cell therapies may provide structural and functional benefits after stroke. However, the effects of these treatments are not yet fully understood and are the subject of continuing investigation. Meanwhile, different clinical trials for stroke, the majority of them small, nonrandomized, and uncontrolled, have been reported, and their results indicate that cell therapy seems safe and feasible in these conditions. In the last 2 years, the number of published and registered trials has dramatically increased. Here, we review the main findings available in the field, with emphasis on the clinical results. Moreover, we address some of the questions that have been raised to date, to improve future studies.

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.

PET/CT and vascular disease: current concepts.

Since its introduction in 2001, positron emission tomography associated to computed tomography (PET/CT) has been established as a standard tool in cancer evaluation. Being a multimodality imaging method, it combines in a single session the sensitivity granted by PET for detection of molecular targets within the picomolar range, with an underlying submilimetric resolution inherent to CT, that can precisely localize the PET findings. In this last decade, there have been new insights regarding the pathophysiology of atherosclerosis, particularly about plaque rupture and vascular remodeling. This has increased the interest for research on PET/CT in vascular diseases as a potential new diagnostic tool, since some PET molecular targets could identify diseases before the manifestation of gross anatomic features. In this review, we will describe the current applications of PET/CT in vascular diseases, emphasizing its usefulness in the settings of vasculitis, aneurysms, vascular graft infection, aortic dissection, and atherosclerosis/plaque vulnerability. Although not being properly peripheral vascular conditions, ischemic cardiovascular disease and cerebrovascular disease will be briefly addressed as well, due to their widespread prevalence and importance.

Safety of autologous bone marrow mononuclear cell transplantation in patients with nonacute ischemic stroke.

AIMS: To assess the safety and feasibility of intra-arterial transplantation of autologous bone marrow mononuclear cells in patients with middle cerebral artery ischemic stroke within 90 days of symptom onset. PATIENTS & METHODS: Six patients were included in the study, and they received 1-5 × 10(8) bone marrow mononuclear cell and were evaluated using blood tests, neurological and imaging examination before treatment, and 1, 3, 7, 30, 60, 90, 120 and 180 days after transplantation. Scintigraphies were carried out 2 and 24 h after the procedure to analyze the biodistribution of labeled cells. Electroencephalogram was conducted within 7 days after transplantation. RESULTS: No patients exhibited any complication or adverse events during the procedure. There was no worsening in the neurological scales until the end of the follow-up. CONCLUSION: Intra-arterial bone marrow mononuclear cell transplantation is feasible and safe in patients with nonacute ischemic strokes of the middle cerebral artery. Further studies are required to evaluate the efficacy of this therapy.

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.

Assessment of breast lesions with diffusion-weighted MRI: comparing the use of different b values.

OBJECTIVE: Our purpose was to study the utility of diffusion-weighted MRI in differentiating benign from malignant breast lesions by assessing the best b values. SUBJECTS AND METHODS: Forty-five women (mean age, 46.1 years) with 52 focal mass breast lesions underwent diffusion-weighted imaging with different b values. The apparent diffusion coefficient (ADC) value of each lesion was calculated from the ADC maps done using five b values (0, 250, 500, 750, and 1,000 s/mm(2)) and using b values of 0 s/mm(2) with each other b value separately (0 and 250 s/mm(2), 0 and 500 s/mm(2), 0 and 750 s/mm(2), 0 and 1,000 s/mm(2)). The mean ADC values were correlated with imaging findings and histopathologic diagnoses. The cutoff ADC value, sensitivity, and specificity of diffusion-weighted imaging to differentiate benign and malignant lesions were calculated in all b value combinations. A p value of < 0.05 was considered statistically significant. RESULTS: The mean ADC value was significantly lower for malignant lesions compared to benign lesions (p < 0.0001) in all b value combinations. No statistical difference was seen between the ADC obtained from different b value combinations (p = 0.2581) in the differentiation between benign and malignant lesions. The ADC calculated from b 0 and 750 s/mm(2) was slightly better than the other b value combinations, showing a sensitivity of 92.3% and a specificity of 96.2%. CONCLUSION: Diffusion-weighted imaging is a potential resource as a coadjutant of MRI in the differentiation between benign and malignant lesions. Such imaging can be performed without a significant increase in examination time, especially because it can be done with lower b values.

Sentinel lymph node identification in breast cancer: a comparison study of deep versus superficial injection of radiopharmaceutical.

OBJECTIVES: Sentinel lymph node biopsy (SLNB) has been performed for purposes of disease staging. SLN is usually located in the axillary region and internal mammary chain (IMC). Metastasis in internal mammary nodes can be an important prognostic factor and an indication for systemic treatment in patients with small carcinomas. The SLNB technique continues to evolve and the proper radiopharmaceutical injection route remains under discussion. This study evaluated the success rate of deep injection to identify axillary and extra-axillary SLNs and compared the results with superficial injection technique. METHODS: Forty-six patients diagnosed with breast cancer (stages I and II) were submitted to radiopharmaceutical injection. Deep injection of technetium-99m-dextran 500 was carried out in 20 patients (group A) and periareolar injection of technetium-99m-phytate was carried out in 26 patients (group B). All SLNs were studied by imprint cytology and hematoxylin and eosin staining. RESULTS: SLN identification rate was 76.1% (35 of 46). The SLN identification rate was 75% (15 of 20) for group A and 76.9% (20 of 26) for group B. Axillary SLNs were identified in 65% (13 of 20) of group A and 76.9% (20 of 26) of group B, with no statistical difference (P = 0.75). Extra-axillary SLNs were only identified in group A, and IMC was the principal extra-axillary location. CONCLUSION: Deep injection of radiopharmaceutical achieved a good SLN identification rate in axillary and extra-axillary locations and it is an important method for detecting IMC sentinel nodes.

Whole-body MRI and FDG PET fused images for evaluation of patients with cancer.

OBJECTIVE: The purpose of this article is to illustrate the feasibility of fused whole-body MRI and PET for the evaluation of patients with cancer. CONCLUSION: MRI has proven to be superior to CT for studying several regions of the body, and PET FDG has become an established diagnostic tool in oncology. Because FDG accumulates avidly in tumor tissue, fusing FDG PET to whole-body MRI allows good anatomy-based evaluation of disease.

Radioguided breast surgery for occult lesion localization - correlation between two methods.

BACKGROUND: The detection of sub-clinical breast lesions has increased with screening mammography. Biopsy techniques can offer precision and agility in its execution, as well as patient comfort. This trial compares radioguided occult lesion localization (ROLL) and wire-guided localization (WL) of breast lesions. We investigate if a procedure at the ambulatorial level (ROLL) could lead to a better aesthetic result and less postoperative pain. In addition, we intend to demonstrate the efficacy of radioguided localization and removal of occult breast lesions using radiopharmaceuticals injected directly into the lesions and correlate radiological and histopathological findings. METHODS: One hundred and twenty patients were randomized into two groups (59 WL and 61 ROLL). The patients were requested to score the cosmetic appearance of their breast after surgery, and a numerical rating scale was used to measure pain on the first postoperative day. Clearance margins were considered at > or = 10 mm for invasive cancer, > or = 5 mm for ductal carcinoma in situ, and > or = 1 mm for benign disease. Patients were subsequently treated according to the definitive histological result. When appropriate, different statistical tests were used in order to test the significance between the two groups, considering a P value < 0.05 as statistically significant. RESULTS: WL and ROLL located all the occult breast lesions successfully. In the ROLL group, the specimen volume was smaller and there were more cases with clear margins (P < 0.05). There were significant differences in mean time of hospital stay between WL and ROLL (21.42 vs. 2.56 hours), but not in operative time (39.4 vs. 29.9 minutes). There were significant differences in the subjective ease of the procedures as rated by the patients (cosmetic outcomes and postoperative pain). CONCLUSION: ROLL is an effective method for the excision of non-palpable breast lesions. It enables more careful planning of the cutaneous incision, leading to better aesthetic results, less postoperative symptoms, and smaller volumes of excised tissue.