Tracer Injection Research Articles

Biodistribution, Safety Profile, and Radiation Dosimetry of [18F]SYN2, a PET Cardiac Perfusion Tracer, in Healthy Subjects.

A first-in-human phase I clinical study aimed to assess the safety profile, radiation dosimetry, and biodistribution of a potential cardiac PET myocardial perfusion imaging tracer, [18F]SYN2 (18F-labeled acridine derivative), in healthy subjects. Methods: [18F]SYN2 intravenous administration with PET imaging was performed on healthy volunteers, and sequential whole-body imaging was performed over 4 h. Blood and urine samples were collected for up to 240 min. Safety follow-up visits took place at 2, 5, and 14 d after the administration. Results: Ten subjects (8 women and 2 men) completed all study procedures. The mean age was 38.1 ± 8.8 y, and the mean body mass index was 22.7 ± 3.0 kg/m2 The mean administered dose of radioactivity was 258 MBq (range, 246-272 MBq). There were no drug-related adverse events, and the tracer was well tolerated in all subjects. The mean whole-body effective radiation dose for [18F]SYN2 was 0.0195 mSv/MBq. The tracer was rapidly taken up by the myocardial wall and cleared from plasma, leading to good image quality within minutes of tracer injection. Conclusion: On the basis of the safety profile, radiation dosimetry, and biodistribution of [18F]SYN2, it appears to be a promising agent for clinical PET myocardial perfusion imaging and to warrant further clinical studies.

Dual-Phase C-11 PiB PET Images for Detecting Tau Pathology in Cerebral Amyloid Angiopathy.

Cerebral amyloid angiopathy (CAA) is a major cause of lobar intracerebral hemorrhage and cognitive dysfunction in the elderly, and frequently coexists with Alzheimer's disease and tau pathology. Dual-phase 11C-PiB PET detects amyloid deposition and cerebral perfusion changes and may have diagnostic value for identifying tau in CAA. We prospectively enrolled patients with probable CAA for dynamic PiB and AV1451 scans. We compared early-phase (0-6 min after tracer injection) and late-phase (40-70 min) PiB PET between the tau(+) and tau(-) groups (based on AV1451 PET) and investigated their diagnostic values for detecting tau. CAA/tau(+) had lower early-phase temporal PiB uptake than CAA/tau(-) (p = 0.014) and higher late-phase uptake in the whole cortex and temporal and parietal lobes (all p < 0.05). Early-phase temporal PiB SUVR correlated with tau burden (r = -0.34, p = 0.038). Using Youden's cut-off, early-phase and late-phase PET had sensitivities of 55% and 80% and specificities of 85% and 65% for detecting tau, respectively. Combining early- and late-phase scans provided a rule-out sensitivity of 90% and rule-in specificity of 100% for tau pathology in CAA. Dual-phase 11C-PiB PET represents a reliable approach for assessing tau and could potentially identify CAA patients for tau biomarker testing.

The Appearance of a Secondary Bone Lesion in Place of Nonspecific Vertebral Anomalies Related to Mediastinal Venous Thrombosis: Coincidence?

A 66-year-old woman with locally advanced lung adenocarcinoma underwent FDG-PET/CT, which revealed superior vena cava invasion and thrombosis of the brachiocephalic veins. Tracer injection on the side of thrombosis demonstrated hypermetabolism in the dorsal spine, likely due to collateral venous drainage. Following chemoradiotherapy and early discontinuation of immunotherapy for toxicity, she developed cervicobrachial neuralgia 18 months later. MRI showed marrow replacement lesions and FDG-PET/CT identified bone recurrence at D1, correlating with previously nonspecific fixation abnormalities. This case raises the question of whether vertebral venous stasis may favor metastatic grafting and highlights the potential need for contralateral FDG injection.

IL13Rα2-Targeting Antibodies for Immuno-PET in Solid Malignancies.

Interleukin-13 receptor α-2 (IL13Rα2) is a cell surface receptor frequently expressed in solid malignancies, such as glioblastoma and melanoma, with limited expression in healthy tissue, rendering it an ideal target for noninvasive and specific tumor delineation. In this study, we report the development of 5 novel IL13Rα2-targeted human monoclonal antibodies (mAbs) KLG-1-5; in subsequent invitro and invivo studies after radiolabeling with 89Zr, we evaluate their performance to identify a lead candidate. Methods: Five novel human anti-IL13Rα2 mAbs KLG-1-5 were developed and invitro binding properties and target specificity assessed. In vivo 89Zr-immuno-PET using KLG-1-5 was conducted in a subcutaneous U-87 MG glioblastoma mouse model, and a mass dose titration study was conducted with lead candidate KLG-3. Ex vivo biodistribution results were used to derive prospective dosimetry of 177Lu-labeled KLG-3. Targeting with KLG-3 was also verified in an A-375 melanoma model using the optimized conditions determined in the U-87 MG xenograft model. Results: In vitro studies confirmed target specificity and pico- to low nanomolar binding affinity. Immuno-PET studies with KLG-1-5 in U-87 MG xenografts demonstrated continuously increasing tumoral uptake with maximal uptake at 144 h after tracer injection, clearance of the unbound tracer from the blood pool, and little uptake in any other normal tissues, leading to high-contrast images. KLG-3 provided the highest tumoral uptake and tumor-to-normal tissue ratios and was chosen as the lead candidate, and further dose optimization with this antibody led to tumoral uptake of 97 ± 6 maximum percent of injected dose per gram at 144 h after tracer injection. Ex vivo biodistribution-derived prospective dosimetry for 177Lu-labeled KLG-3 predicted a favorable therapeutic index, encouraging the development of IL13Rα2-targeted radioimmunotherapy. Of note, KLG-3 performed similarly well in a melanoma model, emphasizing the versatility of this antibody. Conclusion: Lead candidate anti-IL13Rα2 mAb KLG-3 validated highly specific target binding in human glioblastoma and melanoma models, resulting in high-contrast PET images with minimal accumulation in off-target healthy tissues. Prospective dosimetry of its 177Lu-labeled counterpart suggested therapeutic efficacy at relatively low injected activities, supporting further pursuit of KLG-3 in future translational radioimmunotherapy applications.

Impaired cerebrospinal fluid circulation and cerebral lymphatic drainage in a rat model of chronic hydrocephalus.

The cerebrospinal fluid (CSF) not only protects the brain but also maintains homeostasis by removing metabolic waste produced by brain activity. This study hypothesizes that chronic CSF circulatory dysfunction, such as chronic hydrocephalus or normal pressure hydrocephalus (NPH), may be a critical condition in neurodegenerative diseases associated with metabolic waste accumulation. To investigate the CSF circulation and cerebral lymphatic drainage in a rat model of chronic hydrocephalus induced by kaolin injection, we performed time-dependent evaluations of intraparenchymal injection of tracers as well as intraventricular injection of Evans blue. The study systemically evaluated the dysfunction of CSF circulation and lymphatic drainage in the brain from various perspectives, including the glymphatic system, transependymal CSF flow, subarachnoid CSF flow, meningeal lymphatic drainage, and peripheral lymphatic drainage to deep cervical lymph nodes. The results indicated delayed CSF circulation, including glymphatic system, and cerebral lymphatic drainage in the kaolin-induced chronic hydrocephalus model. Based on these findings, our research indicated that dysfunction of CSF circulation, as observed in conditions such as chronic hydrocephalus or NPH, may act as an initiating or exacerbating factor in neurodegenerative diseases. This can lead to the accumulation of metabolic waste, as seen in Alzheimer's disease. Our research can help identify risk factors and provide insight into the underlying pathophysiology of neurodegenerative diseases, which may lead to the development of novel therapeutic strategies.

Research on the inversion of coal reservoir physical property parameters and water flow characteristics based on tracer concentration model

This paper established a tracer concentration model considering the strong adsorption performance of coal reservoirs. Then, combined with the tracer injection and monitoring results of the well groups (Block 1 and Block 2, abbreviated as B1 and B2), the physical property parameters of the reservoir were inverted to achieve the description of groundwater flow in coal reservoirs. The results show that the tracer concentration model consistently fits the tracer concentration curves of each inner well. The overall Freundlich adsorption constant and permeability of the reservoir in the B1 are both high, resulting in a delay in the initial time and an advance in the final time of monitoring the tracer concentration in the production well. The reservoir water in B1 flows in the northeast-to-southwest direction, and the reservoir water in B2 flows in the east-to-northwest direction. Hydrogen and oxygen isotope test results show that the reservoir water supply mainly comes from atmospheric precipitation infiltrated from the surface, so the flow direction of the reservoir water is primarily consistent with the terrain trend. The results of this work are essential to optimizing the coalbed methane development and drainage gas recovery measures.

Imaging CDK4/6 Broaden Options of Breast Cancer Diagnostics with Positron Emission Tomography.

This study developed a novel PET radiotracer to screen breast cancer patients sensitive to CDK4/6 inhibitors, guiding personalized treatment. Two CDK4/6-targeting precursors were synthesized and evaluated in vitro and in vivo. Three breast cancer cell lines─MCF-7, MDA-MB-231, and MDA-MB-468─were selected based on decreasing sensitivity to palbociclib. Compared to [68Ga]Ga-DOTA-Hexa-CDKi, [68Ga]Ga-DOTA-Bua-CDKi clearly identified cell lines with high sensitivity to palbociclib. PET/CT imaging showed significantly higher uptake of [68Ga]Ga-DOTA-Bua-CDKi (8.40 ± 0.85%ID/g) in MCF-7 tumors 60 min after tracer injection, with significant differences in tumor uptake among the three models (P < 0.05). Blocking assays demonstrated specific tumor uptake of [68Ga]Ga-DOTA-Bua-CDKi. Biosafety tests validated its safety as a diagnostic agent. [68Ga]Ga-DOTA-Bua-CDKi showed highly specific targeting of CDK4/6 and effective contrast imaging in tumor models. To our knowledge, [68Ga]Ga-DOTA-Bua-CDKi is one of the first radiotracers to assess CDK inhibitor sensitivity, offering promise for evaluating patient responses to CDK4/6 inhibitors.

99mTc]Tc-MY6349 Probe for Trop2-Targeted SPECT Imaging: From Preclinical to Pilot Clinical Study.

The trophoblast cell-surface antigen 2 (Trop2) is markedly overexpressed in breast cancers, with a particularly high incidence in triple-negative breast cancer. The therapeutic relevance of Trop2 expression is underscored by the approval of an antibody-drug conjugate for triple-negative breast cancer treatment. However, there is no a predictive technique for accurate whole-body mapping of Trop2 expression in patients. In this study, we developed a novel Trop2-specific molecular probe, [99mTc]Tc-MY6349, and evaluated its safety and feasibility for detecting Trop2 expression in breast cancer using SPECT/CT imaging. Methods: Trop2 expression in different breast cancer cell lines was assessed via immunofluorescence and flow cytometry. The Trop2-specific nanobody MY6349 was site-specifically labeled with 99mTc via a C-terminal GGGC tag, and its binding affinity to the Trop2 receptor was tested invitro. The invivo tumor uptake and distribution of [99mTc]Tc-MY6349 were examined through SPECT imaging and biodistribution studies. Furthermore, a pilot clinical study of [99mTc]Tc-MY6349 SPECT/CT was conducted in 8 patients with breast cancer, and the results were compared with [18F]FDG PET/CT. Results: [99mTc]Tc-MY6349 achieved a greater than 95% radiochemical purity after purification. In vitro and invivo experiments demonstrated the binding specificity of [99mTc]Tc-MY6349 to the Trop2 receptor. In vivo imaging and biodistribution studies revealed a significant correlation between tumor uptake and Trop2 expression levels. In the pilot clinical study, SPECT imaging with [99mTc]Tc-MY6349 successfully detected Trop2-positive tumors 15 min after tracer injection. Delayed imaging showed reduced uptake in normal organs but sustained retention of [99mTc]Tc-MY6349 in tumors. Importantly, [99mTc]Tc-MY6349 SPECT/CT imaging highlighted Trop2 expression heterogeneity and visualized primary and metastatic lesions with a favorable tumor-to-background ratio in breast cancer. Conclusion: [99mTc]Tc-MY6349 was successfully prepared and exhibited a high binding affinity and Trop2 specificity. The pilot clinical study validated the safety and feasibility of [99mTc]Tc-MY6349 SPECT/CT for detecting Trop2 expression invivo in patients with breast cancer. This imaging modality could complement existing methods, aiding in the guidance of Trop2-targeted therapies and advancing personalized treatment while also promoting the application of SPECT/CT nuclear medicine imaging technology.

XTR003, a fatty acid metabolism PET tracer: A phase I study to evaluate the safety, biodistribution, radiation dosimetry, and pharmacokinetics in healthy volunteers.

XTR003 is a novel 18F-labeled fatty acid PET tracer to image myocardial fatty acid metabolism that can be potentially used to assess myocardial viability for ischemic heart disease. This Phase I study evaluated its safety, biodistribution, radiation dosimetry, and pharmacokinetics. Ten healthy Chinese volunteers (mean age of 28.4±4.6 years, 3 females) were intravenously injected with XTR003 (296-370 MBq) at rest and monitored for adverse events on the day of injection and follow-up days. Multiple whole-body PET images were acquired within 290minutes and processed to investigate the biodistribution and radiation dosimetry. Whole blood, plasma, and urine were collected simultaneously for 420minutes to evaluate the pharmacokinetics with the measurement of radioactivity. Only two treatment-related adverse events occurred with no severe adverse effects. After tracer injection, XTR003 in the plasma peaked at 2.883minutes as .0108235% of injected dose per gram (%ID/g) and reduced to the minimum at 30minutes. The 0-20minutes whole-body PET images indicated that both heart and liver were two critical organs with the highest percentage of injected dose (%ID) (4.37±.66 and 48.76±4.17 %ID). Specifically, XTR003 demonstrated high initial uptake in the heart, with sustained retention for up to 290minutes (standardized uptake value: 6.50±2.54 at 0-20minutes and 5.89±2.18 at 270-290minutes). The whole-body effective radiation dose was 17μSv/MBq. The cumulative urinary excretion was 9.009%. XTR003, as an18F-labeled radiotracer, was safe and well-tolerated. The rapid uptake and prolonged retention of XTR003 in the heart show promise for evaluating myocardial fatty acid metabolism. The Phase II clinical trial to explore the efficacy of XTR003 for detecting myocardial viability should be warranted. ClinicalTrials.gov Identifier: NCT05136391.

Developing a Two‐Dimensional Semi‐Analytical Solution on a Plan View for a Consecutive Divergent Tracer Test Considering Regional Groundwater Flow

ABSTRACTMultiple successive tracer tests are often conducted to obtain reliable breakthrough curve results under regional groundwater flow, especially when the accuracy is crucial. In such cases, the period of rest between the end of the first divergent tracer test and the initiation of the second divergent tracer test allows the tracer from the first test to travel along with the background regional flow, thereby influencing the distribution of residual tracer concentration. This residual tracer could potentially interfere with breakthrough curve results from the tracer injection in the second tracer test. Additionally, the conventional analytical solution used for the divergent tracer test considers only radial flow; regional flow and consecutive tracer tests are ignored. Consequently, interpreting the behaviour of the tracer in consecutive divergent tracer tests under regional flow conditions is challenging using conventional measures because of background regional concentration. This study proposes a new semi‐analytical solution, considering the effects of divergent radial and regional flows in consecutive tracer tests, addressing a critical gap in the conventional analytical solutions that, despite their practical necessity, have not been previously developed. The proposed semi‐analytical solution was subjected to parameter studies under various scenarios. In our case studies, the conventional analytical solution based on a single tracer test can be safely used for parameter estimation only in cases where the injected mass for the subsequent tracer test is approximately six‐fold that of the first tracer test or if the drift time is longer than 10 days.

Abstract TP397: Effect of Intracranial Pressure Spikes Modeling Subarachnoid Aneurysm Rupture on the Brain and Dura Barrier Immune System

Steep intracranial pressure (ICP) rise constitutes a hallmark of aneurysmal subarachnoid hemorrhage (SAH). While during aneurysm rupture there are multiple simultaneous triggers that can initiate an inflammatory response, in this study we isolate the impact of a single ICP spike on the brain and meningeal barriers and the resulting secondary injury. Using a rodent model, we induced an ICP spike through cisterna magna injection of artificial cerebrospinal fluid or autologous blood, with simultaneous ICP monitoring. We then assessed the innate immune response in the brain parenchyma and dura using immunohistochemistry and multiparameter flow cytometry. Glia limitans integrity was evaluated via intrathecal injection of the SR101 tracer, and microthrombi presence was assessed using intravenous fluorescent fibrin. Upregulated pathways were identified through bulk RNA sequencing. Our findings revealed that a single ICP spike exerts global effects on brain and meningeal barrier immunology, potentially leading to secondary injury. Histological analysis and flow cytometry of dura whole mounts showed extensive cell death of resident CD206+ macrophages, essential for steady-state immune surveillance, alongside infiltration of Ly6C+ pro-inflammatory monocytes and Ly6G+ neutrophils, indicating a robust acute response to the ICP spike. In the brain parenchyma, we observed minimal infiltration of circulating immune cells, consistent with the effects of aneurysm rupture. However, diffuse microglia clustering suggested multifocal parenchymal injury. Additionally, there was evidence of widespread glia limitans disruption and microthrombi formation in the brain parenchyma. Bulk RNA sequencing supported these findings, demonstrating upregulation of MyD88 and TNFα pathways in the dura, which were absent in the brain. In conclusion, this study demonstrates that a single ICP spike triggers significant meningeal inflammation, disrupts steady-state dura immune surveillance, and causes diffuse parenchymal injury with glia limitans disruption. These results highlight a novel blood-independent pathway of injury following aneurysm rupture, offering new insights into potential therapeutic targets.

Self-supervised segmentation and characterization of fiber bundles in anatomic tracing data.

Anatomic tracing is the gold standard tool for delineating brain connections and for validating more recently developed imaging approaches such as diffusion MRI tractography. A key step in the analysis of data from tracer experiments is the careful, manual charting of fiber trajectories on histological sections. This is a very time-consuming process, which limits the amount of annotated tracer data that are available for validation studies. Thus, there is a need to accelerate this process by developing a method for computer-assisted segmentation. Such a method must be robust to the common artifacts in tracer data, including variations in the intensity of stained axons and background, as well as spatial distortions introduced by sectioning and mounting the tissue. The method should also achieve satisfactory performance using limited manually charted data for training. Here we propose the first deep-learning method, with a self-supervised loss function, for segmentation of fiber bundles on histological sections from macaque brains that have received tracer injections. We address the limited availability of manual labels with a semi-supervised training technique that takes advantage of unlabeled data to improve performance. We also introduce anatomic and across-section continuity constraints to improve accuracy. We show that our method can be trained on manually charted sections from a single case and segment unseen sections from different cases, with a true positive rate of ~0.80. We further demonstrate the utility of our method by quantifying the density of fiber bundles as they travel through different white-matter pathways. We show that fiber bundles originating in the same injection site have different levels of density when they travel through different pathways, a finding that can have implications for microstructure-informed tractography methods. The code for our method is available at https://github.com/v-sundaresan/fiberbundle_seg_tracing.

Basal Forebrain Projections to the Retrosplenial and Cingulate Cortex in Rats.

The basal forebrain (BF) plays a crucial role in modulating cortical activation through its widespread projections across the cortical mantle. Previous anatomical studies have demonstrated that each cortical region receives a specific projection from the BF. In this study, we examined BF cholinergic and non-cholinergic projections to the retrosplenial cortex (RSC) and anterior cingulate cortex (ACC) using two retrograde tracers, Fast Blue (FB) and Fluoro-Gold (FG), in combination with choline acetyltransferase (ChAT) immunostaining in rats. The RSC and ACC receive cholinergic and non-cholinergic projections mainly from the medial part of the horizontal limb of the diagonal band (HDB) and the vertical limb of the diagonal band (VDB). The main difference of BF projections to the RSC, ACC, and prelimbic cortex (PL) is that the ACC and PL receive projections from the rostral half of the medial globus pallidus (GP), whereas the RSC receives stronger non-cholinergic projections from the VDB and medial septum (MS). As the injection site shifts from rostral (PL) to caudal (RSC) through the ACC, the strong GP and weak MS/VDB projections of non-cholinergic neurons are reversed. Cholinergic projection neurons make up a similar proportion of the total projection neurons in both ACC (37%) and RSC (33%) injections. Double retrograde tracer injections in the RSC and ACC revealed a small number of double-labeled projection neurons in the MS/VDB and HDB. These findings indicate that the ACC and RSC receive both spatially overlapping and differential projections from the BF, with the cholinergic and non-cholinergic projections varying between BF subregions and different rostrocaudal cortical regions.

Early-phase 18F-Flortaucipir tau-PET as a proxy of brain metabolism in Alzheimer's disease: a comparison with 18F-FDG-PET and early-phase amyloid-PET.

As dual-phase amyloid-PET can evaluate amyloid (A) and neurodegeneration (N) with a single tracer injection, dual-phase tau-PET might be able to provide both tau (T) and N. Our study aims to assess the association of early-phase tau-PET scans and 18F-fluorodeoxyglucose (FDG) PET and their comparability in discriminating Alzheimer's disease (AD) patients and differentiating neurodegenerative patterns. 58 subjects evaluated at the Geneva Memory Center underwent dual-phase 18F-Flortaucipir-PET with early-phase acquisition (eTAU) and 18F-FDG-PET within 1 year. A subsample of 36 participants also underwent dual-phase amyloid-PET (eAMY). Standardized uptake value ratios (SUVRs) were calculated to assess the correlation of eTAU and their respective 18F-FDG-PET and eAMY scans. Hypometabolism and hypoperfusion maps and their spatial overlap were also evaluated at the individual level visually and semiquantitatively. Receiver operating characteristic analyses were performed to compare the discriminative power of eTAU, FDG, and eAMY SUVR between A-/T- and A+/T + participants. Strong positive correlations were found between eTAU and FDG SUVRs (r = 0.84, p < 0.001) and eTAU and eAMY SUVRs (r > 0.87, p < 0.001). Clusters of significant hypoperfusion with good correspondence to hypometabolism topographies were found at the individual level, independently of the underlying neurodegenerative patterns. Both eTAU and FDG SUVRs significantly distinguished A+/T + from A-/T- individuals (AUCeTAU=0.604, AUCFDG=0.748) with FDG performing better than eTAU (p = 0.04). eAMY and eTAU SUVR showed comparable discriminative power. Early-phase 18F-Flortaucipir-PET can provide perfusion information closely related to brain regional glucose metabolism and perfusion measured by early-phase amyloid-PET, even if less accurate than FDG-PET as a biomarker for neurodegeneration.

Surgery impairs glymphatic activity and cognitive function in aged mice

Delirium is a common complication in elderly surgical patients and is associated with an increased risk of dementia. Although advanced age is a major risk factor, the mechanisms underlying postoperative delirium remain poorly understood. The glymphatic system, a brain-wide network of perivascular pathways, facilitates cerebrospinal fluid (CSF) flow and supports the clearance of metabolic waste. Impairments in glymphatic function have been observed in aging brains and various neurodegenerative conditions. Using in vivo two-photon imaging, we examined the effects of surgery (laparotomy) on glymphatic function in adult (6 months) and aged (18 months) mice 24 h post-surgery. In adult mice, CSF tracer entry into the brain parenchyma along periarteriolar spaces occurred rapidly following intracisternal tracer injection, with no significant differences between sham and surgery groups. In contrast, aged mice exhibited delayed tracer influx, with further impairments observed in the surgery group compared to sham controls. This glymphatic dysfunction correlated with poorer T-maze performance in aged mice. These findings suggest that surgery exacerbates glymphatic impairment in aging brains, potentially hindering brain waste clearance and contributing to postoperative delirium.

Experimental studies of dispersed phase axial dispersion in pulsed sieve plate columns

ABSTRACT Residence time distribution of the dispersed phase in a 40 mm diameter pulsed sieve plate column is measured with a pulse tracer injection technique and the axial dispersion coefficient E D, calculated. Water is chosen as the dispersed phase and n-dodecane as the continuous phase. Dependence of E D on phase velocities, pulse velocity Af and geometrical parameters – perforation diameter d, fractional-free area of the sieve plate, and plate spacing is investigated. The ED vs Af plots show either a change in slope or a local maximum at the transition from mixer-settler to emulsion regime. The effect of perforation diameter d on E D is mediated by the pulse velocity Af. At low Af, E D increases with d, but for Af > 11 mm/s, E D is insensitive to d. E D is found to have inverse relationships with the fractional free area and plate spacing. However, the decrease in E D with S depends on the pulse velocity Af and the superficial velocity of the dispersed phase. Experimental results are fitted to various correlations for E D available in the published literature, with the best fit as quantified through relative error is found for the correlation proposed by Srinikethan et al.

Physical exercise prevents age‐related changes in [11C]PK11195 uptake in a mouse model of Down Syndrome

AbstractBackgroundDown syndrome (DS) is associated with mitochondrial dysfunction leading to higher levels of oxidative stress and cell degeneration. This fact, together with the overexpression of AD‐related genes in trisomy 21, increases the risk of developing Alzheimer's disease (AD). Thus, it is important to look for interventions that could prevent mitochondrial damage before symptoms occur. Physical activity is a non‐pharmacological intervention that provides an anti‐inflammatory response and increases the levels of neurotrophic factors that are beneficial for brain health. Therefore, the aim of this study is to evaluate the effect of physical activity on microglial function during the aging process in a transgenic mouse model of DS using [11C]PK11195 positron emission tomography.MethodTs65Dn male and female mice (euploid and trisomic) were used in this study (CEUA 1292/2019). Animals were subjected to physical activity on a treadmill from 2 to 20 months of age, 3 times per week. [11C]PK11195 PET images were acquired at 5, 14, and 20 months of age. For image acquisition, animals were injected intravenously with [11C]PK11195. Images were acquired in a small animal PET scanner 30 min after tracer injection, and acquisition took 20 min, with animals kept under anesthesia throughout the acquisition. PET images were co‐registered to a T2‐MRI template and the standardized uptake value (SUV) was calculated in the whole brain.ResultThroughout the aging process, a decrease in the [11C]PK11195 uptake was observed in the trisomic animals at 20 months of age, when compared to the age of 5 months (‐60.7%, 0.56±0.13 vs. 0.22±0.1, p&lt;0.05); and 14 months (‐55.1%, 0.49±0.09 vs. 0.22±0.1, p&lt;0.01). However, the exercised trisomic animals did not present a decrease in the [11C]PK11195 uptake at 20 months being comparable (no statistical differences) to the euploid animals (exercise and non‐exercise groups).ConclusionOur data suggest that physical activity could prevent a possible deleterious effect of accelerated aging in mitochondrial function, in the presence of the trisomy 21, since lower [11C]PK11195 uptake could be associated with mitochondrial dysfunction and reduced expression of the TSPO protein.

Extensive skin ecchymosis and discolouration following retroareolar injection of magnetic tracer for the axillary lymphatic mapping in breast cancer.

Extensive skin ecchymosis and discolouration following retroareolar injection of magnetic tracer for the axillary lymphatic mapping in breast cancer.

Neuroarchitecture of the Central Complex in the Madeira Cockroach Rhyparobia maderae: Tangential Neurons.

Navigating in diverse environments to find food, shelter, or mating partners is an important ability for nearly all animals. Insects have evolved diverse navigational strategies to survive in challenging and unknown environments. In the insect brain, the central complex (CX) plays an important role in spatial orientation and directed locomotion. It consists of the protocerebral bridge (PB), the central body with upper (CBU) and lower division (CBL), and the paired noduli (NO). As shown in various insect species, the CX integrates multisensory cues, including sky compass signals, wind direction, and ego-motion to provide goal-directed vector output used for steering locomotion and flight. While most of these data originate from studies on day-active insects, less is known about night-active species such as cockroaches. Following our analysis of columnar and pontine neurons, the present study complements our investigation of the cellular architecture of the CX of the Madeira cockroach by analyzing tangential neurons. Based on single-cell tracer injections, we provide further details on the internal organization of the CX and distinguished 27 types of tangential neuron, including three types of neuron innervating the PB, six types of the CBL, and 18 types of the CBU. The anterior lip, a brain area unknown in flies and highly reduced in bees, and the crepine are strongly connected to the cockroach CBU in contrast to other insect species. One tangential neuron of the CBU revealed a direct connection between the mushroom bodies and the CBU.

Subcutaneous Staining of the Breast from Superparamagnetic Iron Oxide Nanoparticle Tracer Injection.

Subcutaneous Staining of the Breast from Superparamagnetic Iron Oxide Nanoparticle Tracer Injection.