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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.

Objective To bring awareness and close gaps between dermatologists and radiologists about the contribution of imaging techniques for diagnosis, treatment, and follow-up of hidradenitis suppurativa (HS). Data sources Investigators searched the PubMed database for articles on HS and radiology techniques. Study selection Databases were searched up to December 2018. The query retrieved 257 publications, of which 103 were unique; of these, 7 were inaccessible. From the remaining 96, 33 were irrelevant (did not discuss HS lesion features). After applying the inclusion criteria, 63 studies were relevant to this study. Data extraction A standardized form was constructed to extract data from eligible studies by two independent authors. Data synthesis Imaging techniques are significant and useful tools in HS management. Imaging should be carried out to evaluate disease severity, subclinical features, treatment success, and intraoperative patient assessment. Providers should consider nonconventional radiology techniques, which are underused in clinical management of HS. Further, dermatology and radiology require a shared terminology of disease features to better understand patient status. Conclusions Publications on HS lesion imaging have increased over the years. Imaging techniques have proven useful for determining HS severity and treatment effectiveness, as well as intraoperative patient assessment. These authors strongly recommend the use of these techniques in routine clinical practice for patients with HS.

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. HIGHLIGHTS Adaptations in validated methods are a recurrent trend due to limited budgets which does not diminish their functionality. Scintigraphy with 99mTcO4 is effective in evaluating the functionality of thyroid grafts after cryopreservation in rats. It is possible to adapt human SPECT for other animals for clinical and research purposes.

Purpose We analyzed the effect of the use of Eye Protective Equipment (EPE) and the best position to use individual dosimeters to estimate the eye lens radiation dose to a medical staff that works with yttrium-90. Methods Three Alderson-Head-Phantoms were exposed to 58 MBq of 90Y for 24 h, in two different experiments: (1) at different dosimeter placements and (2) with and without the use of EPE. The measurements were carried on by thermoluminescent technique. Results Doses received by dosimeters on both lenses were more closely represented by the ones placed between the eyes than those on the temples, which underestimated the doses by a factor of 3. Also, the transmission factors showed that the EPE was able to reduce the Hp(3) values from about 78% to 92%. Conclusions This study demonstrated that the use of EPE can optimize the 90Y eye lens dose. An individual dosimeter should be worn between the eyes for an appropriate estimate of this equivalent dose.

OBJECTIVE Tumor necrosis factor-alpha (TNF-α) is an important inflammatory cytokine. 99mTc-anti-TNF-α antibody scintigraphy has proven to be a viable alternative to MRI in specific cases. The objective of this study was to evaluate the performance of scintigraphy with 99mTc-anti-TNF-α in the identification of inflammatory foci in individuals diagnosed with rheumatoid arthritis using MRI as the gold standard. METHODS This cross-sectional, descriptive and analytical-qualitative clinical study compared the performance of 99mTc-anti-TNF-α scintigraphy with that of MRI with intravenous administration of gadolinium (used as the gold standard) and a clinical examination (Disease Activity Score 28) in 220 joints of 20 patients with a diagnosis of rheumatoid arthritis and one healthy control. RESULTS The concordance of scintigraphy with MRI in individuals with a diagnosis of rheumatoid arthritis was 79%. The accuracy, sensitivity and specificity of scintigraphy for distinguishing between inflammatory and noninflammatory sites were 92, 89, and 93%, respectively. No adverse reactions to the examinations were reported. CONCLUSIONS Scintigraphy with 99mTc-anti-TNF-α was well-tolerated and had a good ability to distinguish between inflammatory and noninflammatory lesions in patients with rheumatoid arthritis.

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.

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 (1×106ASC+HA 1%) should be considered for subsequent studies and may be an alternative to dermal fillers due to the expected lasting effects.

Background Even though mesenchymal stromal cells (MSCs) mitigate lung and distal organ damage in experimental polymicrobial sepsis, mortality remains high. We investigated whether preconditioning with eicosapentaenoic acid (EPA) would potentiate MSC actions in experimental sepsis by further decreasing lung and distal organ injury, thereby improving survival. Methods In C57BL/6 mice, sepsis was induced by cecal hligation and puncture (CLP); sham-operated animals were used as control. Twenty-four hours after surgery, CLP mice were further randomized to receive saline, adipose tissue-derived (AD)-MSCs (105, nonpreconditioned), or AD-MSCs preconditioned with EPA for 6 h (105, EPA-preconditioned MSCs) intravenously. After 24 h, survival rate, sepsis severity score, lung mechanics and histology, protein level of selected biomarkers in lung tissue, cellularity in blood, distal organ damage, and MSC distribution (by technetium-99m tagging) were analyzed. Additionally, the effects of EPA on the secretion of resolvin-D1 (RvD1), prostaglandin E2 (PGE2), interleukin (IL)-10, and transforming growth factor (TGF)-β1 by MSCs were evaluated in vitro. Results Nonpreconditioned and EPA-preconditioned AD-MSCs exhibited similar viability and differentiation capacity, accumulated mainly in the lungs and kidneys following systemic administration. Compared to nonpreconditioned AD-MSCs, EPA-preconditioned AD-MSCs further reduced static lung elastance, alveolar collapse, interstitial edema, alveolar septal inflammation, collagen fiber content, neutrophil cell count as well as protein levels of interleukin-1β and keratinocyte chemoattractant in lung tissue, and morphological abnormalities in the heart (cardiac myocyte architecture), liver (hepatocyte disarrangement and Kupffer cell hyperplasia), kidney (acute tubular necrosis), spleen (increased number of megakaryocytes and lymphocytes), and small bowel (villi architecture disorganization). EPA preconditioning of MSCs resulted in increased secretion of pro-resolution and anti-inflammatory mediators (RvD1, PGE2, IL-10, and TGF-β). Conclusions Compared to nonpreconditioned cells, EPA-preconditioned AD-MSCs yielded further reductions in the lung and distal organ injury, resulting in greater improvement in sepsis severity score and higher survival rate in CLP-induced experimental sepsis. This may be a promising therapeutic approach to improve outcome in septic patients. Electronic supplementary material The online version of this article (10.1186/s13287-019-1365-z) contains supplementary material, which is available to authorized users.

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.

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.

The release of liquid effluents containing radionuclides from radioactive plants in urban areas has been the subject of discussions related to the environmental issue. This study presents the analysis of the activity concentrations (AC) of 131I and 99mTc in sewage samples collected in a nuclear medicine facility (NMF), associated with an university hospital situated in Rio de Janeiro, Brazil. The analyzes and measurements by gamma spectrometry of the collected sewage samples were performed, whose the estimated values (EV) for AC obtained for 131I in July (8.78 × 103 Bq m-3) and September 2016 (9.80 × 103 Bq m-3) and in February 2017 (1.14 × 104 Bq m-3) were lower than the exemption level (EL = 1.90 × 104 Bq m-3). For 99mTc, the EV for AC obtained from August (4.77 × 102 Bq m-3 and 2.96 × 104 Bq m-3) to September 2017 (2.18 × 103 Bq m-3) were lower than the EL (1.90 × 109 Bq m-3). From an environmental point of view, the presence of 131I in the sewage treatment unit (STU), even if below the legal release limit, points out the greater importance of this radionuclide, as it requires special precautions in its adequate storage for the radioactive decay in the NMF and the dilution effect to reduce its AC minimizing the environmental impact after the effluent release to the environment. The presence of 131I in the STU was not expected pointing to the need and evaluation of the waste management system (WMS) of the NMF.

A busca por eficiência na triagem de pacientes com indicativo de infecção por COVID-19 tem impulsionado pesquisadores de diversas áreas no desenvolvimento de sistemas de apoio, com particular ênfase noaprendizado profundo. Neste trabalho, consideramos as imagens de Raio-X de tórax, que são segmentadas para identificar os pulmões como região de interesse. Para tal, o modelo MultiResUnet é utilizado, obtendo um Índice de Jaccard de 93,34% e Coeficiente Dice de 96,53%. As imagens segmentadas alimentaram três modelos profundos com diferentes níveis de complexidade sendo um baseado em uma Máquina de Vetores de Suporte ( SVM) do tipo Classe Única. Os modelos de aprendizado profundo apresentaram desempenho superior, quando comparados ao SVM, obtendo uma sensibilidade de 98% para a identificação da COVID-19. Porém, observou-se que o aumento da complexidade não propiciou ganhos expressivos de desempenho.

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.

This work aims to compare SPECT (Single Photon Emission Tomography Computed) and planar modalities as the most efficient methodology to perform dosimetry by molecular imaging. Twenty-one male C57BL6 mice induced with murine melanoma cell line B16-F10, administered 131I-Ixolaris were used for melanoma therapy. The procedures applied to them followed the standards described for the use of experimental animals, duly approved by the National Council for Animal Experimentation Control (CONCEA from Federal University of Rio de Janeiro. The accumulated activities were obtained in order to estimate the absorbed doses in each organ. Mass and metabolic differences between mice and humans were considered and used to extrapolate data acquired at different scales. From the dose factors provided by the MIRDOSE software, the absorbed doses in the target organs irradiated by the source organs were calculated and, finally, the effective dose was estimated. From the Student's t-hypothesis test performed in the accumulated activity, absorbed dose and S-factor quantities, there is no statistically significant difference between performing the image dosimetry from SPECT and planar acquired images.

Mammary adenocarcinomas with metastases are more common in dogs than in cats. Their incidence is 1 in every 4,000 cats. In routine veterinary practice, laboratory exams for diagnosis of these neoplasms are nonspecific and scarcely used. Even though invasive procedure, biopsy, and histopathological findings are the gold standards that define the clinical approach, the clinical evaluation, and image assessment lead the way to the proper treatment, especially when surgical intervention is a possibility. This study describes the clinical signs, histopathological aspects, radiological and scintigraphic findings of a cat with mammary adenocarcinoma and metastases evaluated one hour after intravenous administration of 99mTc-thymine. Our focus was not to discuss the pathological aspects of the disease but the Nuclear Medicine role in metastases detection. Metastases, when lesser than 4mm, could go unnoticed by radiological exams, whereas scintigraphy may detect them. Using 99mTc-thymine scintigraphy, we successfully detected unsuspected metastases in the lungs, liver, and right kidney. Early diagnosis is the key to a better rate of survival due to the given treatment and prognostic. Hence, we strongly recommend the use of 99mTc-thymine scintigraphy as a complementary tool for breast cancer diagnosis in veterinary care.

Background Despite recent advances in understanding its pathophysiology and development of novel therapies, asthma remains a serious public health issue worldwide. Combination therapy with inhaled corticosteroids and long-acting β2-adrenoceptor agonists results in disease control for many patients, but those who exhibit severe asthma are often unresponsive to conventional treatment, experiencing worse quality of life, frequent exacerbations, and increasing healthcare costs. Bone marrow-derived mononuclear cell (BMMC) transplantation has been shown to reduce airway inflammation and remodeling and improve lung function in experimental models of allergic asthma. Methods This is a case series of three patients who presented severe asthma, unresponsive to conventional therapy and omalizumab. They received a single intravenous dose of autologous BMMCs (2 × 107) and were periodically evaluated for 1 year after the procedure. Endpoint assessments included physical examination, quality of life questionnaires, imaging (computed tomography, single-photon emission computed tomography, and ventilation/perfusion scan), lung function tests, and a 6-min walk test. Results All patients completed the follow-up protocol. No serious adverse events attributable to BMMC transplantation were observed during or after the procedure. Lung function remained stable throughout. A slight increase in ventilation of the right lung was observed on day 120 after BMMC transplantation in one patient. All three patients reported improvement in quality of life in the early post-procedure course. Conclusions This paper described for the first time the effects of BMMC therapy in patients with severe asthma, providing a basis for subsequent trials to assess the efficacy of this therapy.

Intracerebral hemorrhage (ICH) is as a life-threatening condition that can occur in young adults, often causing long-term disability. Recent preclinical data suggests 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 to 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.\ud \ud

Yttrium-90 (90Y) is one of the most widely used radionuclides in Nuclear Medicine practice. However, characteristic energy of this beta emitter constitutes a difficulty for dose planning using SPECT imaging. This work aimed to study bremsstrahlung X-rays effects produced by 90Y beta particles during SPECT image acquisition using Monte Carlo code MCNPX. Several simulations were carried out to evaluate different aspects that could affect SPECT image quality, such as: collimator type, source-collimator distance and composition of each interacting material. Two configurations of 90Y sources were simulated: a point source in several spheres of different materials (soft tissue, water, articular cartilage, and bone) and dimensions with radius ranging from 1 to 20 mm; and a uniformly distributed source in a Lucite cylindrical phantom filled with water. It was evaluated the bremsstrahlung photon emission generated inside different materials; for this was considered the number photons that passing through every different sphere's surface for each radii and material. In case of cylindrical phantom filled with water, in order to obtain the energy deposited over NaI (Tl) crystal detector; there was considered Median Energy General Purpose (MEGP) and Low Energy High Resolution (LEHR) collimators. Moreover, using TMESH routine available in the MCNPX Monte Carlo code, energy distribution images according to the collimator type and the source-collimator distance were obtained. The simulation was validated by comparing with the spectral distribution of the 90Y bremsstrahlung X-rays obtained experimentally from an acrylic cylindrical phantom. Results corroborated the importance of Monte Carlo simulation method to evaluate a performance of SPECT image acquisition with 90Y. The best resolution was obtained with MEGP collimator independent of source-collimator distance.

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(

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.

This is a pilot clinical study primarily designed to assess the feasibility and safety of X-ray-guided percutaneous intraspinal injection of allogeneic canine adipose tissue-derived mesenchymal stem cells in dogs with chronic spinal cord injury. Six dogs with chronic paraplegia (≥six months) were intraparenchymally injected with allogeneic cells in the site of lesion. Cells were obtained from subcutaneous adipose tissue of a healthy dog, cultured to passage 3, labeled with 99mTechnetium, and transplanted into the lesion by percutaneous X-ray-guided injection. Digital X-ray efficiently guided cell injection as 99mTechnetium-labeled cells remained in the injection site for at least 24 hours after transplantation. No adverse effects or complications (infection, neuropathic pain, or worsening of neurological function) were observed during the 16-week follow-up period after transplantation. Three animals improved locomotion as assessed by the Olby scale. One animal walked without support, but no changes in deep pain perception were observed. We conclude that X-ray-guided percutaneous intraspinal transplantation of allogeneic cells in dogs with chronic spinal cord injury is feasible and safe. The efficacy of the treatment will be assessed in a new study involving a larger number of animals.

Background/Aims: We investigated the regenerative capacity of intravenous administration of bone marrow–derived mononuclear cells (BMMCs) in a rat model of bilateral renal ischemia/reperfusion (IR) injury and the involvement of inflammatory anti-inflammatory and other biological markers in this process. Methods: Rats were subjected to 1h bilateral renal pedicle clamping. BMMCs were injected i.v 1h after reperfusion and tracked by 99mTc and GFP+ BMMCs. Twenty-four hours after reperfusion, renal function and histological changes were evaluated. The mRNA (real time PCR) and protein (ELISA and immuno-staining) expression of biological markers were analyzed. Results: Renal function and structure improved after infusion of BMMCs in the IR group (IR-C). Labeled BMMCs were found in the kidneys after therapy. The expression of inflammatory and biological markers (TLR-2, TRL-4, RAGE, IL-17, HMGB-1, KIM-1) were reduced and the expression of anti-inflammatory and antioxidant markers (IL-10, Nrf2, and HO-1) were increased in IR-C animals compared with IR untreated animals (IR-S). The apoptotic index diminished and the proliferation index increased in IR-C compared with IR-S. Conclusion: The results contribute to our understanding of the role of different biological players in morphofunctional renal improvement and cytoprotection in a post-ischemic reperfusion kidney injury model subjected to cellular therapy.

In vitro-expanded bone marrow stromal cells (BMSCs) have long been proposed for the treatment of complex bone-related injuries because of their inherent potential to differentiate into multiple skeletal cell types, modulate inflammatory responses, and support angiogenesis. Although a wide variety of methods have been used to expand BMSCs on a large scale by using good manufacturing practice (GMP), little attention has been paid to whether the expansion procedures indeed allow the maintenance of critical cell characteristics and potency, which are crucial for therapeutic effectiveness. Here, we described standard procedures adopted in our facility for the manufacture of clinical-grade BMSC products with a preserved capacity to generate bone in vivo in compliance with the Brazilian regulatory guidelines for cells intended for use in humans. Bone marrow samples were obtained from trabecular bone. After cell isolation in standard monolayer flasks, BMSC expansion was subsequently performed in two cycles, in 2- and 10-layer cell factories, respectively. The average cell yield per cell factory at passage 1 was of 21.93±12.81×106 cells, while at passage 2, it was of 83.05±114.72×106 cells. All final cellular products were free from contamination with aerobic/anaerobic pathogens, mycoplasma, and bacterial endotoxins. The expanded BMSCs expressed CD73, CD90, CD105, and CD146 and were able to differentiate into osteogenic, chondrogenic, and adipogenic lineages in vitro. Most importantly, nine out of 10 of the cell products formed bone when transplanted in vivo. These validated procedures will serve as the basis for in-house BMSC manufacturing for use in clinical applications in our center.

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.

Radiosynoviorthesis (RSO) is a minimally invasive treatment aiming for the necrosis of the pannus tissue by the use of radionuclide. The method suggested here starts with the segmentation of the joint effusion, synovial thickness, and area of the synovial membrane using the 3D Slicer software. The last step is the estimated value of the activity to be injected without considering the leakage of the radiopharmaceutical into the articular cavity. It includes the S-values obtained by Monte Carlo simulation coupled with the calculated therapeutic distance (ST90).

The aims of this study were to construct a mouse model based on experimental data and to evaluate two approaches for a radiation dosimetry study on the development of a new radiopharmaceutical based on MIRD Formalism with free software. The first one obtaining S-values from a reference model and with these data calculating the absorbed doses. The second consisting of a specific anatomy mouse considering characteristics such as strain, gender, age, and weight used in preclinical studies comparing the results obtained for the new radiopharmaceutical 99mTc-Ixolaris. A voxelized mouse model (C57BL/6 lineage) based on Computed Tomography images with ten segmented organs was developed by 3D SLICER software and was used as input in GATE Monte Carlo simulations (version 7.1) to determine organ absorbed dose distribution by the proposed approaches. The first method consisted of obtaining the S-values for each source organ by performing separate simulations, and the second method obtained the absorbed dose in each target organ through a single simulation containing all source organs (real radiopharmaceutical biodistributions). Absorbed dose distribution volumetric maps were obtained for each simulation. Using the first method, the numerical data were extracted from volumetric maps to determine the S-values for each source organ and in the second method the absorbed dose was obtained directly from simulation, without S-value tables. The preclinical dosimetry evaluation showed good agreement between both methods but each one has its own advantages and disadvantages: the first has less statistical uncertainties than the second method and the S-values obtained for a standard model can be scaled to other mouse sizes; the second method requires shorter simulation computational time, considering a specific anatomy mouse, using a real biodistribution with all source organs in the simulation without construction of S-value tables.

Introducao: A avaliacao da distribuicao de material radioativo na articulacao por imagens SPECT pos radiosinoviortese (RSO) com Itrio-90 visa garantir a eficacia e seguranca da terapia. Contudo, a qualidade de imagem por Bremsstrahlung possui grandes limitacoes, tornando necessarios estudos sobre a otimizacao de parâmetros de aquisicao SPECT e dos metodos de reconstrucao de imagem para o radionuclideo Itrio-90. Metodos: Foram obtidas imagens SPECT de um simulador de acrilico contendo quatro insercoes cilindricas de diferentes diâmetros que mimetizam lesoes captantes, com colimadores de alta, media e baixa (HEGP, MEGP e LEHR) energia, janela de energia de 130 keV, largura 70% e matriz 64 x 64. Os metodos de reconstrucao utilizados foram FBP e OSEM, com aplicacao de diferentes filtros e numero de iteracoes. Resultados: O maior contraste de imagem foi observado para o metodo de reconstrucao iterativo , com a aplicacao do filtro Gauss, sendo que o metodo FBP apresentou resultados insatisfatorios. O acrescimo no numero de iteracoes no metodo OSEM nao apresentou aumento da qualidade da imagem. Ha menor discrepância entre os valores de captacao das diferentes lesoes para as aquisicoes com o colimador HEGP. Conclusoes:. Ha diferenca significativa na quantificacao entre as reconstrucoes FBP e OSEM. O uso do colimador HEGP e do metodo de reconstrucao iterativo OSEM com a aplicacao do filtro Gauss se mostrou como o protocolo de aquisicao de imagem mais indicado para estudos com 90 Y.

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

This work evaluates the relationship between ultrasonic reflection and bone density from fourteen cylindrical bovine cortical bone samples (3.0-cm thick).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).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.IRC was sensitive to bone density variation.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).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).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.O IRC foi sensível à variação da densidade óssea.

Despite advances in technology and rehabilitation, no effective therapies are available for patients with SCI, which remains a major medical challenge. This study compared the efficacy of 3 different doses of mesenchymal stem cells (MSCs) administered by intraperitoneal injection as a therapeutic strategy for compressive SCI. We used adult female C57BL/6 mice that underwent laminectomy at the T9 level, followed by spinal-cord compression for 1 min with a 30-g vascular clip. The animals received an intraperitoneal (i.p.) injection of MSCs (8 × 104, 8 × 105 or 8 × 106 in 500 μl) or DMEM (500 μl), one week after SCI. The cells of the three MSC doses administered i.p. were able to migrate to the injury site, increase local expression of trophic factors, and enhance fiber sparing and/or regeneration, accompanied by substantial improvement in locomotor performance. Cell transplantation at 8 × 105 density showed the best therapeutic potential, leading to significant tissue and functional improvements compared to the other two doses. These findings indicate that i.p. application of MSCs at the density of 8 × 105 yielded the best results, suggesting that this dose is a good choice for SCI treatment.

Bone mineral density is an important parameter for the diagnosis of bone diseases, as well as for predicting fractures and treatment monitoring. Thus, the aim of the present study was to evaluate the potential of Quantitative Ultrasound (QUS) to monitor bone changes after calcium, phosphorus, and magnesium loss in rat femurs in vitro during a demineralization process. Four quantitative ultrasound parameters were estimated from bone surface echoes in eight femur diaphysis of rats. The echo signals were acquired during a decalcification process by Ethylenediaminetetraacetic Acid (EDTA). The results were compared to Quantitative Computed Tomography (QCT) and inductively coupled plasma optical emission spectrometry measurements for validation. Integrated Reflection Coefficient (IRC) reflection parameters and Frequency Slope of Reflection Transfer Function (FSRTF) during demineralization tended to decrease, while the backscattering parameter Apparent Integrated Backscatter (AIB) increased and Frequency Slope of Apparent Backscatter (FSAB) showed an oscillatory behavior with no defined trend. Results indicate a clear relation between demineralization and the corresponding decrease in the reflection parameters and increase in the scattering parameters. The trend analysis of the fall curve of the chemical elements showed a better relationship between IRC and QCT. It was possible to monitor bone changes after ions losses, through the QUS. Thus, it is an indication that the proposed protocol has potential to characterize bone tissue in animal models, providing consistent results towards standardization of bone characterization studies by QUS endorsing its use in humans.

The objective of this study was to evaluate spatial resolution and the influence of different reconstruction methods in a FLEX Triumph ™ Pre-Clinical Imaging System images applied to mice C57BL6 dosimetry in a new radiopharmaceuticals development for humans use. CT and SPECT images were obtained from a homemade phantom containing four spheres with diameters (d) simulating iodine-accumulating injuries at University Hospital (HU / UFRJ). The SPECT images were reconstructed with filtered back projection method (FBP) and the influence in resolution and partial volume effect was evaluated for different filters: Hamming, Hann and Ramp. The resolution found was 9.3 to 9.4 mm, significantly lower than the value provided by the manufacturer, 1.6 mm. Thus, the protocol for mice can be optimized by FBP reconstruction method and Hamming filter, 0.5 cut-off , yielding a resolution from 9.3 to 9.4 mm. This value indicates that iodine-accumulating regions diameter below 9.3 mm is not quantifiable.