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The labeling of stem cells with radionuclides allows in vivo monitoring of cell migration and homing. Here, we describe the labeling of mononuclear stem cells with 99mTc and show their biodistribution in preclinical models and patients with chronic kidney disease.

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To verify the viability and functionality of cryopreserved thyroid autotransplantation in rats who underwent total thyroidectomy in the treatment of postoperative hypothyroidism. Thirty-two Wistar rats were randomly assigned into groups (G) with eight animals each: control (CG); simulation (SG); hypothyroidism (HTG) and transplanted (TG). At the beginning and in the 13th week of the experiment, serum levels of total T3, free T4, TSH and calcium were determined. In both the first and 14th weeks, scintigraphic examinations, 99m-Tc pertechnetate radioisotope biodistribution and histopathology were performed. In the 14th week, the expression of proliferating cell nuclear antigen (PCNA) and cellular apoptosis (caspase-3) were also evaluated. In the 13th week, the transplanted animals had normal serum levels of total T3 and free T4. TSH levels showed a tendency towards normality. In the 14th week, scintigraphic exams displayed graft isotopic uptake in all animals in the TG group. Histological examinations 13 weeks after transplantation showed the viability and functionality of thyroid follicles. PCNA revealed significant immunoreactivity of the graft (p < 0.001) when the TG was compared to the CG. There was no difference between CG and TG considering the expression of activated caspase-3. The experimental study confirmed the viability and functionality of thyroid autotransplantation implanted in skeletal muscle with evidence of cell proliferation without cellular apoptosis. This surgical strategy was effective in the treatment of postoperative hypothyroidism.

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PURPOSE: Recently, there has been a growing interest in a methodology for dose planning in radiosynoviorthesis to substitute fixed activity. Clinical practice based on fixed activity frequently does not embrace radiopharmaceutical dose optimization in patients. The aim of this paper is to propose and discuss a dose planning methodology considering the radiological findings of interest obtained by three-dimensional magnetic resonance imaging combined with Monte Carlo simulation in radiosynoviorthesis treatment applied to hemophilic arthropathy. METHOD: The parameters analyzed were: surface area of the synovial membrane (synovial size), synovial thickness and joint effusion obtained by 3D MRI of nine knees from nine patients on a SIEMENS AVANTO 1.5 T scanner using a knee coil. The 3D Slicer software performed both the semiautomatic segmentation and quantitation of these radiological findings. A Lucite phantom 3D MRI validated the quantitation methodology. The study used Monte Carlo N-Particle eXtended code version 2.6 for calculating the S-values required to set up the injected activity to deliver a 100 Gy absorbed dose at a determined synovial thickness. The radionuclides assessed were: 90Y, 32P, 188Re, 186Re, 153Sm, and 177Lu, and the present study shows their effective treatment ranges. RESULT: The quantitation methodology was successfully tested, with an error below 5% for different materials. S-values calculated could provide data on the activity to be injected into the joint, considering no extra-articular leakage from joint cavity. Calculation of effective treatment range could assist with the therapeutic decision, with an optimized protocol for dose prescription in RSO. CONCLUSION: Using 3D Slicer software, this study focused on segmentation and quantitation of radiological features such as joint effusion, synovial size, and thickness, all obtained by 3D MRI in patients' knees with hemophilic arthropathy. The combination of synovial size and thickness with the parameters obtained by Monte Carlo simulation such as effective treatment range and S-value, from which is calculated the injected activity, could be used for treatment planning in RSO. Data from this methodology could be a potential aid to clinical decision making by selecting the most suitable radionuclide; justifying the procedure, fractioning the dose, and the calculated injected activity for children and adolescents, considering both the synovial size and thickness.

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Rheumatoid arthritis (RA) is an autoimmune disease, which is associated with systemic and chronic inflammation of the joints, resulting in synovitis and pannus formation. For several decades, the assessment of RA has been limited to conventional radiography, assisting in the diagnosis and monitoring of disease. Nevertheless, conventional radiography has poor sensitivity in the detection of the inflammatory process that happens in the initial stages of RA. In the past years, new drugs that significantly decrease the progression of RA have allowed a more efficient treatment. Nuclear Medicine provides functional assessment of physiological processes and therefore has significant potential for timely diagnosis and adequate follow-up of RA. Several single photon emission computed tomography (SPECT) and positron emission tomography (PET) radiopharmaceuticals have been developed and applied in this field. The use of hybrid imaging, which permits computed tomography (CT) and nuclear medicine data to be acquired and fused, has increased even more the diagnostic accuracy of Nuclear Medicine by providing anatomical localization in SPECT/CT and PET/CT studies. More recently, fusion of PET with magnetic resonance imaging (PET/MRI) was introduced in some centers and demonstrated great potential. In this article, we will review studies that have been published using Nuclear Medicine for RA and examine key topics in the area.

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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.

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AIMS: To assess the biodistribution of bone marrow mononuclear cells (BMMNC) delivered by different routes in patients with subacute middle cerebral artery ischemic stroke. PATIENTS & METHODS: This was a nonrandomized, open-label Phase I clinical trial. After bone marrow harvesting, BMMNCs were labeled with technetium-99m and intra-arterially or intravenously delivered together with the unlabeled cells. Scintigraphies were carried out at 2 and 24 h after cell transplantation. Clinical follow-up was continued for 6 months. RESULTS: Twelve patients were included, between 19 and 89 days after stroke, and received 1-5 × 10(8) BMMNCs. The intra-arterial group had greater radioactive counts in the liver and spleen and lower counts in the lungs at 2 and 24 h, while in the brain they were low and similar for both routes. CONCLUSION: BMMNC labeling with technetium-99m allowed imaging for up to 24 h after intra-arterial or intravenous injection in stroke patients.

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Intravascular delivery of cells has been increasingly used in stroke models and clinical trials. We compared the biodistribution and therapeutic effects of bone marrow mononuclear cells (BMMCs) delivered by intra-arterial (IA) or intravenous (IV) injection after cortical ischemia. For the biodistribution analyses, BMMCs were labeled with (99m)Technetium ((99m)Tc). At 2 h, gamma-well counting of the brain and of the other organs evaluated did not show differences between the non-ischemic and ischemic groups or between injection routes, and the organs with the highest uptake were the liver and lungs, with low uptake in the brain. At 24 h, the liver maintained the highest activity, and a marked decrease was seen in pulmonary uptake in all groups. At this time point, although the activity in the brain remained low, the lesioned hemisphere showed greater homing than the contralateral hemisphere, for both the IV and IA ischemic groups. Histological analysis by CellTrace labeling indicated similar homing between both routes in the peri-infarct region 24 h after transplantation and functional recovery was observed in both groups up to 11 weeks after the lesion. In conclusion, transplantation of BMMCs by IA or IV routes may lead to similar brain homing and therapeutic efficacy after experimental stroke.

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