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Most follicular cell-derived differentiated thyroid carcinomas are regarded as low-risk neoplasms prompting conservative therapeutic management. Here, we provide consensus recommendations reached by a multidisciplinary group of endocrinologists, medical oncologists, pathologists, radiation oncology specialists, a surgeon and a medication reimbursement specialist, addressing more challenging forms of this malignancy, focused on radioactive iodine (RAI)-resistant or -refractory differentiated thyroid carcinoma (RAIRTC). In this document we highlight clinical, radiographic, and molecular features providing the basis for these management plans. We distinguish differentiated thyroid cancers associated with more aggressive behavior from thyroid cancers manifesting as poorly differentiated and/or anaplastic carcinomas. Treatment algorithms based on risk-benefit assessments of different multimodal therapy approaches are also discussed. Given the scarcity of data supporting management of this rare yet aggressive disease entity, these consensus recommendations provide much needed guidance for multidisciplinary teams to optimally manage RAIRTC.

BackgroundDiabetic retinopathy (DR) affects about 25% of people with diabetes in Canada. Early detection of DR is essential for preventing vision loss. ObjectiveWe evaluated the real-world performance of an artificial intelligence (AI) system that analyzes fundus images for DR screening in a Quebec tertiary care center. MethodsWe prospectively recruited adult patients with diabetes at the Centre hospitalier de l’Université de Montréal (CHUM) in Montreal, Quebec, Canada. Patients underwent dual-pathway screening: first by the Computer Assisted Retinal Analysis (CARA) AI system (index test), then by standard ophthalmological examination (reference standard). We measured the AI system's sensitivity and specificity for detecting referable disease at the patient level, along with its performance for detecting any retinopathy and diabetic macular edema (DME) at the eye level, and potential cost savings. ResultsThis study included 115 patients. CARA demonstrated a sensitivity of 87.5% (95% CI 71.9-95.0) and specificity of 66.2% (95% CI 54.3-76.3) for detecting referable disease at the patient level. For any retinopathy detection at the eye level, CARA showed 88.2% sensitivity (95% CI 76.6-94.5) and 71.4% specificity (95% CI 63.7-78.1). For DME detection, CARA had 100% sensitivity (95% CI 64.6-100) and 81.9% specificity (95% CI 75.6-86.8). Potential yearly savings from implementing CARA at the CHUM were estimated at CAD $245,635 (US $177,643.23, as of July 26, 2024) considering 5000 patients with diabetes. ConclusionsOur study indicates that integrating a semiautomated AI system for DR screening demonstrates high sensitivity for detecting referable disease in a real-world setting. This system has the potential to improve screening efficiency and reduce costs at the CHUM, but more work is needed to validate it.

A trustful relationship between transplant patients and their transplant team (interpersonal trust) is essential in order to achieve positive health outcomes and behaviors. We aimed to 1) explore variability of trust in transplant teams; 2) explore the association between the level of chronic illness management and trust; 3) investigate the relationship of trust on behavioral outcomes. A secondary data analysis of the BRIGHT study (ID: NCT01608477; https://clinicaltrials.gov/ct2/show/NCT01608477?id=NCT01608477&rank=1) was conducted, including multicenter data from 36 heart transplant centers from 11 countries across four different continents. A total of 1,397 heart transplant recipients and 100 clinicians were enrolled. Trust significantly varied among the transplant centers. Higher levels of chronic illness management were significantly associated with greater trust in the transplant team (patients: AOR= 1.85, 95% CI = 1.47–2.33, p < 0.001; clinicians: AOR = 1.35, 95% CI = 1.07–1.71, p = 0.012). Consultation time significantly moderated the relationship between chronic illness management levels and trust only when clinicians spent ≥30 min with patients. Trust was significantly associated with better diet adherence (OR = 1.34, 95%CI = 1.01–1.77, p = 0.040). Findings indicate the relevance of trust and chronic illness management in the transplant ecosystem to achieve improved transplant outcomes. Thus, further investment in re-engineering of transplant follow-up toward chronic illness management, and sufficient time for consultations is required.

Pipelines are a critical component of transportation infrastructure. They offer the safest and most efficient way to transport large volumes of oil and natural gas from development areas to refineries and consumers. Landslides can damage pipelines resulting in a spill of a toxic substance. However, landslide hazards to pipelines and other infrastructure can be significantly reduced, if the location of landslides is known and the appropriate mitigation measures are taken in advance. Traditional, ground-based methods for mapping areas susceptible to landslides can be expensive and limited. Radar interferometry is a remote sensing technique that measures ground deformation from two Synthetic Aperture Radar (SAR) images. Time series of ground deformation computed from repeatedly acquired SAR data allows us to detect slow-moving, deep-seated landslides over a large area with high spatial resolution and precision. European Space Agency’s Sentinel-1 satellite systematically collects SAR data worldwide, and large datasets have been collected since approximately 2016–2017. A combination of improved availability of SAR data, inexpensive processing power and advanced processing techniques designed for large datasets provides an opportunity to map ground deformation on a regional scale. The study’s objective is to compare deformation maps, as proxies for landslide identification, computed from commercial RADARSAT-2 data and freely available Sentinel-1 data over a region in northeast British Columbia, Canada, with an extensive network of pipelines. It is concluded that readily available Sentinel-1 data can produce high-quality deformation maps capable of detecting slow-moving landslides. In the study area, hundreds of slow-moving landslides are mapped using hotspot analysis based on Getis–Ord Gi∗ statistics, and two small regions where landslide activity near the pipelines is particularly significant are studied in detail. Field observations also revealed that slope deformation features formed in the surface sediments consist of colluvium derived from a mix of glaciolacustrine, till and fine-grained sedimentary bedrock.

Abstract Peposertib (M3814) is a potent and selective DNA-PK inhibitor in early clinical development. It effectively blocks non-homologous end-joining repair of DNA double-strand breaks (DSB) and strongly potentiates the antitumor effect of ionizing radiation (IR) and topoisomerase II inhibitors. By suppressing DNA-PK catalytic activity in the presence of DNA DSB, M3814 potentiates ATM/p53 signaling leading to enhanced p53-dependent antitumor activity in tumor cells. Here, we investigated the therapeutic potential of M3814 in combination with DSB-inducing agents in leukemia cells and a patient-derived tumor. We show that in the presence of IR or topoisomerase II inhibitors, M3814 boosts the ATM/p53 response in acute leukemia cells leading to the elevation of p53 protein levels as well as its transcriptional activity. M3814 synergistically sensitized p53 wild-type, but not p53-deficient, AML cells to killing by DSB-inducing agents via p53-dependent apoptosis involving both intrinsic and extrinsic effector pathways. The antileukemic effect was further potentiated by enhancing daunorubicin-induced myeloid cell differentiation. Further, combined with the fixed-ratio liposomal formulation of daunorubicin and cytarabine, CPX-351, M3814 enhanced the efficacy against leukemia cells in vitro and in vivo without increasing hematopoietic toxicity, suggesting that DNA-PK inhibition could offer a novel clinical strategy for harnessing the anticancer potential of p53 in AML therapy.

Increasing evidence suggests that interference with growth factor receptor tyrosine kinase (RTK) signaling can affect DNA damage response (DDR) networks, with a consequent impact on cellular responses to DNA‐damaging agents widely used in cancer treatment. In that respect, the MET RTK is deregulated in abundance and/or activity in a variety of human tumors. Using two proteomic techniques, we explored how disrupting MET signaling modulates global cellular phosphorylation response to ionizing radiation (IR). Following an immunoaffinity‐based phosphoproteomic discovery survey, we selected candidate phosphorylation sites for extensive characterization by targeted proteomics focusing on phosphorylation sites in both signaling networks. Several substrates of the DDR were confirmed to be modulated by sequential MET inhibition and IR, or MET inhibition alone. Upon combined treatment, for two substrates, NUMA1 S395 and CHEK1 S345, the gain and loss of phosphorylation, respectively, were recapitulated using invivo tumor models by immunohistochemistry, with possible utility in future translational research. Overall, we have corroborated phosphorylation sites at the intersection between MET and the DDR signaling networks, and suggest that these represent a class of proteins at the interface between oncogene‐driven proliferation and genomic stability.

Summary: Tepotinib is an oral MET inhibitor approved for metastatic non-small cell lung cancer (NSCLC) harboring MET exon 14 (METex14) skipping mutations. Examining treatment-naive or tepotinib-resistant cells with MET amplification or METex14 skipping mutations identifies other receptor tyrosine kinases (RTKs) that co-exist in cells prior to tepotinib exposure and become more prominent upon tepotinib resistance. In a small cohort of patients with lung cancer with MET genetic alterations treated with tepotinib, gene copy number gains of other RTKs were found at baseline and affected treatment outcome. An Src homology 2 domain-containing phosphatase 2 (SHP2) inhibitor delayed the emergence of tepotinib resistance and synergized with tepotinib in treatment-naive and tepotinib-resistant cells as well as in xenograft models. Alternative signaling pathways potentially diminish the effect of tepotinib monotherapy, and the combination of tepotinib with an SHP2 inhibitor enables the control of tumor growth in cells with MET genetic alterations.

Despite significant advances in the treatment of acute myeloid leukemia (AML) the long-term prognosis remains relatively poor and there is an urgent need for improved therapies with increased potency and tumor selectivity. Mylotarg is the first AML-targeting drug from a new generation of antibody drug conjugate (ADC) therapies aiming at the acute leukemia cell compartment with increased specificity. This agent targets leukemia cells for apoptosis with a cytotoxic payload, calicheamicin, carried by a CD33-specific antibody. Calicheamicin induces DNA double strand breaks (DSB) which, if left unrepaired, lead to cell cycle arrest and apoptosis in cancer cells. However, repair of DSB by the non-homologous end joining pathway driven by DNA-dependent protein kinase (DNA-PK) can reduce the efficacy of calicheamicin. M3814 is a novel, potent and selective inhibitor of DNA-PK. This compound effectively blocks DSB repair, strongly potentiates the antitumor activity of ionizing radiation and DSB-inducing chemotherapeutics and is currently under clinical investigation. Suppressing DSB repair with M3814 synergistically enhanced the apoptotic activity of calicheamicin in cultured AML cells. Combination of M3814 with Mylotarg in two AML xenograft models, MV4-11 and HL-60, demonstrated increased efficacy and significantly improved survival benefit without elevated body weight loss. Our results support a new application for pharmacological DNA-PK inhibitors as enhancers of Mylotarg and a potential new combination treatment option for AML patients.

El consumo de bebidas alcohólicas fue una constante en la vida cotidiana de los habitantes de Puebla durante el Porfiriato. Tanto hombres como mujeres, jóvenes o viejos, solían beber pulque, coñac o aguardiente como manera de sociabilización, por motivos medicinales o simplemente por acompañar sus alimentos. Sin embargo, las élites consideraban que era una práctica alarmante, pues la línea entre el alcohólico consuetudinario y el bebedor social era muy delgada, considerándolos a todos como enfermos. A través del análisis de los documentos producidos por los intelectuales de la época (científicos, liberales y católicos) trataremos de demostrar que existían dos realidades, ya que no todos los alcohólicos eran criminales, ni los bebedores ocasionales presentaban siempre un comportamiento aceptable. De esta manera revisaremos la vida cotidiana en sus aspectos laboral, familiar, educacional, social y eclesiástico.

Abstract Background Hypoxia-induced radioresistance constitutes a major obstacle for a curative treatment of cancer. The aim of this study was to investigate effects of photon and carbon ion irradiation in combination with inhibitors of DNA-Damage Response (DDR) on tumor cell radiosensitivity under hypoxic conditions. Methods Human non-small cell lung cancer (NSCLC) models, A549 and H1437, were irradiated with dose series of photon and carbon ions under hypoxia (1% O2) vs. normoxic conditions (21% O2). Clonogenic survival was studied after dual combinations of radiotherapy with inhibitors of DNA-dependent Protein Kinase (DNAPKi, M3814) and ATM serine/threonine kinase (ATMi). Results The OER at 30% survival for photon irradiation of A549 cells was 1.4. The maximal oxygen effect measured as survival ratio was 2.34 at 8 Gy photon irradiation of A549 cells. In contrast, no significant oxygen effect was found after carbon ion irradiation. Accordingly, the relative effect of 6 Gy carbon ions was determined as 3.8 under normoxia and. 4.11 under hypoxia. ATM and DNA-PK inhibitors dose dependently sensitized tumor cells for both radiation qualities. For 100 nM DNAPKi the survival ratio at 4 Gy more than doubled from 1.59 under normoxia to 3.3 under hypoxia revealing a strong radiosensitizing effect under hypoxic conditions. In contrast, this ratio only moderately increased after photon irradiation and ATMi under hypoxia. The most effective treatment was combined carbon ion irradiation and DNA damage repair inhibition. Conclusions Carbon ions efficiently eradicate hypoxic tumor cells. Both, ATMi and DNAPKi elicit radiosensitizing effects. DNAPKi preferentially sensitizes hypoxic cells to radiotherapy.

Landslides are the most common natural hazard in British Columbia. The province has recorded the largest number of historical landslide fatalities in Canada, and damage to infrastructure comes at a great cost. In order to understand the potential impacts of landslides, radar remote sensing has become a cost-effective method for detecting downslope movements. This study investigates downslope movements in the Southern Interior of British Columbia, Canada, with Sentinel-1 and RADARSAT Constellation Mission (RCM) interferometric synthetic aperture radar (InSAR) data. The 2-dimensional time-series analysis with Sentinel-1 ascending and descending InSAR pairs from October 2017 to June 2021 observed distinct earthflow movements of up to ~15 cm/year in the east–west direction. The Grinder Creek, Red Mountain, Yalakom River, and Retaskit Creek earthflows previously documented are still active, with east–west movements of ~30 cm over the past four years. New RCM data acquired from June 2020 to September 2020 with a 4-day revisit capability were compared to 12-day Sentinel-1 InSAR pairs. The 4-day RCM InSAR pairs at higher spatial resolution showed better performance by detecting relatively small-sized slope movements within a few hundred meters, which were not clearly observed by Sentinel-1. The temporal variabilities observed from the RCM InSAR showed great potential for observing detailed slope movements within a narrower time window.

Background: The microbiome on dental composites has not been studied in detail before. It has not been conclusively clarified whether restorative materials influence the oral microbiome. Methods: We used Illumina Miseq next-generation sequencing of the 16S V1-V2 region to compare the colonisation patterns of bovine enamel (BE) and the composite materials Grandio Flow (GF) and Grandio Blocs (GB) after 48 h in vivo in 14 volunteers. Applying a new method to maintain the oral microbiome ex vivo for 48 h also, we compared the microbiome on GF alone and with the new antimicrobial substance carolacton (GF+C). Results: All in vitro biofilm communities showed a higher diversity and richness than those grown in vivo but the very different atmospheric conditions must be considered. Contrary to expectations, there were only a few significant differences between BE and the composite materials GB and GF either in vivo or in vitro: Oribacterium, Peptostreptococcaceae [XI][G-1] and Streptococcus mutans were more prevalent and Megasphaera, Prevotella oulorum, Veillonella atypica, V. parvula, Gemella morbillorum, and Fusobacterium periodonticum were less prevalent on BE than on composites. In vivo, such preferences were only significant for Granulicatella adiacens (more prevalent on BE) and Fusobacterium nucleatum subsp. animalis (more prevalent on composites). On DNA sequence level, there were no significant differences between the biofilm communities on GF and GF+C. Conclusion: We found that the oral microbiome showed an increased richness when grown on various composites compared to BE in vitro, but otherwise changed only slightly independent of the in vivo or in vitro condition. Our new ex vivo biofilm model might be useful for pre-clinical testing of preventive strategies.

Los estudiantes de medicina de Puebla durante el porfiriato elaboraron seis tesis enfocadas a la psiquiatrí­a. En estos estudios observamos que adoptaron corrientes europeas, especialmente francesas, que los ayudarí­an, a la larga, a desarrollar su práctica médica, pero que al mismo tiempo trataron de enfocarse en problemas locales. A través del estudio del sistema educativo en México y en Puebla, así­ como los autores referenciados por los maestros y alumnos, trataremos de demostrar que buscaron encontrar soluciones a los problemas de la modernidad, como el alcoholismo y la histeria, y propusieron innovaciones en materia terapéutica.

Ipazia è senz'altro una fondamentale figura storica e mitica nel rapporto tra donne e scienza, celebre e studiata da secoli: il suo nome è stato dato nel tempo ad asteroidi e centri di ricerca, la sua vicenda ha dato vita ad opere letterarie ed artistiche. Uccisa ad opera di una folla di fanatici cristiani, monaci-infermieri chiamati parabalani al servizio del vescovo di Alessandria Cirillo, la violenza tragica della sua morte ha contribuito a farne un'eroina che diversi partiti nel tempo hanno adattato alla difesa della loro causa; in particolare, nell'immaginario oggi maggiormente diffuso, Ipazia diviene icona del progresso scientifico contro l'oscurantismo religioso. A partire dallo studio delle fonti e dall'analisi comparata dei maggiori contributi accademici e divulgativi sulla filosofa di Alessandria, basandosi sulla lettura della filosofia antica come pratica di trasformazione di sé inaugurata da Pierre Hadot, e incrociando questa lettura con il bagaglio di analisi storico-critico-epistemologiche sulle costruzioni disciplinari di taglio foucaultiano, si vorrebbe con questo articolo tentare di dare conto della difficoltà e del silenzio caduto sulla particolare configurazione epistemica della diadochè neoplatonica femminile esercitata da Ipazia.

Continuing professional development (CPD) activities are one way that new knowledge can be translated into changes in practice. However, few tools are available for evaluating the extent to which these activities change health professionals' behavior. We developed a questionnaire called CPD-Reaction for assessing the impact of CPD activities on health professionals' clinical behavioral intentions. We evaluated its responsiveness to change in behavioral intention and verified its acceptability among stakeholders.We enrolled 376 health professionals who completed CPD-Reaction before and immediately after attending a CPD activity. We contacted them three months later and asked them to self-report on any behavior change. We compared the mean rankings on each CPD-Reaction construct before and immediately after CPD activities. To estimate its predictive validity, we compared the median behavioral intention score (post-activity) of health professionals reporting a behavior change three months later with the median behavioral intention score of physicians who reported no change. We explored stakeholders' views on CPD-Reaction in semi-structured interviews. Participants were mostly family physicians (62.2%), with an average of 19 years of clinical practice. Post-activity, we observed an increase in intention-related scores for all constructs (P < 0.001) with the most appreciable for the construct beliefs about capabilities. A total of 313 participants agreed to be contacted at follow up, and of these only 69 (22%) reported back. Of these, 43 (62%) self-reported a behavior change. We observed no statistically significant difference in intention between health professionals who later reported a behavior change and those who reported no change (P = 0.30). Overall, CPD stakeholders found the CPD-Reaction questionnaire of interest and suggested potential solutions to perceived barriers to its implementation.The CPD-Reaction questionnaire seems responsive to change in behavioral intention. Although CPD stakeholders found it interesting, future implementation will require addressing barriers they identified.

Mediator-associated kinases CDK8/19 are context-dependent drivers or suppressors of tumorigenesis. Their inhibition is predicted to have pleiotropic effects, but it is unclear whether this will impact on the clinical utility of CDK8/19 inhibitors. We discovered two series of potent chemical probes with high selectivity for CDK8/19. Despite pharmacodynamic evidence for robust on-target activity, the compounds exhibited modest, though significant, efficacy against human tumor lines and patient-derived xenografts. Altered gene expression was consistent with CDK8/19 inhibition, including profiles associated with super-enhancers, immune and inflammatory responses and stem cell function. In a mouse model expressing oncogenic beta-catenin, treatment shifted cells within hyperplastic intestinal crypts from a stem cell to a transit amplifying phenotype. In two species, neither probe was tolerated at therapeutically-relevant exposures. The complex nature of the toxicity observed with two structurally-differentiated chemical series is consistent with on-target effects posing significant challenges to the clinical development of CDK8/19 inhibitors.

El consumo de los habitantes de la región del Río Magdalena, en Sonora México, se ve fuertemente influenciado por sus condiciones climatológicas, comerciales y de vías de comunicación. Mediante la investigación arqueológica de dos ranchos de la primera mitad del siglo XX más el análisis documental de estos se ha podido entender de qué manera estos factores influenciaban la vida de los habitantes del Desierto de Sonora.

La nutrition azotée de différents cultivars de haricot vert a été étudiée en conditions de plein-champ. La variété Aiguillon, plus performante que Royalnel, a mieux répondu à l'inoculation et aux apports de N-combiné. L'inoculation par la souche CIAT 57 a amélioré les biomasses non commercialisables et utiles, la nodulation, la composition azotée etlafixation symbiotique des plantes. Celle-ci a atteint 38 à 49 unités N 2 respectivement pour Royalnel et Aiguillon. Les apports d'azote de démarrage (10 unités (U) au stade 10 jours après levée (JAL)) et post-floral (30 U au stade 60 JAL) ont améliorée la nodulation. Par contre, elle a été inhibée par l'apport de 30 U en début floraison (30 JAL). La dose optimale d'azote combiné a été de 60 U, fractionnées en 10, 30 et 20 U respectivement aux stades 10, 60 et 80 JAL. Les fortes doses d'azote ont donné les bons résultats. Les gousses ont exporté 40 à 4 7 % de N total des plantes dont 1/3 a été d'origine symbiotique , les 2 autres tiers étant d'origine minérale. L'apport tardif effectué au stade 80 JAL a donc été bénéfique à la production des gousses. Mots clés: Phaseolus vulgaris L.-Azote (N-combiné) - Fixation symbiotique - Plein-champ

Description of the preposition dans (in) introducing a PP functioning as a non-finite clause adjunct to the main sentence ("host sentence"), ex In his haste, he impetuously opened the door without knocking. In the same way as other prepositions such as à (to), sur (on), sous (under), devant (before) or face à (in front of), the preposition dans (in) contributes to the expression of a temporal-logical relation of weak consecutivity between a state s expressed by a nominal form in the PP and an event e represented by the host sentence. Dans (in) can then be interpreted as étant donné (given), du fait de (because of). This effect of weak consecutivity is based on the conjunction of a certain number of factors such as 1) the semantic nature of the noun inside the PP, 2) some syntactic features of the PP internal structure, 3) some aspectual conditions concerning the verb and other constituents within the host sentence, necessary to legitimate the interpretation of a consecutivity relation that can be established between a state, expressed by the PP, and an incoming event to be found in the host sentence.

Regenerative medicine, including preclinical studies in large animal models and tissue engineering approaches as well as innovative assays for drug discovery, will require the constant supply of hPSC-derived cardiomyocytes and other functional progenies. Respective cell production processes must be robust, economically viable and ultimately GMP-compliant. Recent research has enabled transition of lab scale protocols for hPSC expansion and cardiomyogenic differentiation towards more controlled processing in industry-compatible culture platforms. Here, advanced strategies for the cultivation and differentiation of hPSCs will be reviewed by focusing on stirred bioreactor-based techniques for process upscaling. We will discuss how cardiomyocyte mass production might benefit from recent findings such as cell expansion at the cardiovascular progenitor state. Finally, remaining challenges will be highlighted, specifically regarding three dimensional (3D) hPSC suspension culture and critical safety issues ahead of clinical translation., (Copyright © 2015 Elsevier B.V. All rights reserved.)

Introduction: A major obstacle in tissue engineering is to create a surgically implantable tissue with long-term viability. Several promising techniques have focused on biological vascularized matrices (BioVaM) with preserved vascular pedicles in the porcine model. However, the handling of this model is time-consuming and expensive. Therefore, our aim was to establish a BioVaM in the rat., Materials and Methods: Small bowel segments of Sprague-Dawley rats were isolated and perfused via cannulation of the superior mesenteric artery and the portal vein. All cellular matrix components were removed by sequential treatment with sodium dodecyl sulfate, sodium deoxycholate, and DNase. Quality of decellularization was investigated by histology and potential residual DNA by spectrophotometry. Primary endothelial cells (ECs) isolated from the major vessels of Sprague-Dawley rats. Cells were labeled with fluorescent cell tracker and injected into the vascular pedicles of the matrix. Attachment of ECs was assessed using fluorescence microscopy of the whole mount., Results: Decellularized matrix demonstrated the absence of cellular components but conserved matrix architecture as determined by immune fluorescent, pentachrome, and hematoxylin and eosin stains. DNA content was reduced by more than 99%. ECs were characterized by specific staining against endothelial nitric oxide synthase and von Willebrand factor; when injected, ECs attached along the vessel walls including the capillaries of the intestinal wall., Conclusions: Rat small bowel segments harvested with intact vascular pedicles and associated vascular network can be successfully decellularized and re-endothelialized ex vivo. This model is an inexpensive and easy to handle alternative and appears to be a promising approach for establishing vascularized tissue constructs., (Georg Thieme Verlag KG Stuttgart · New York.)

Background: (S,S)-[F]FMeNER-D2 is a recently developed norepinephrine transporter ligand which is a potentially useful radiotracer for mapping the brain and heart norepinephrine transporter in vivo using positron emission tomography. In this work, we quantified the biodistribution over time and radiation exposure to multiple organs with (S,S)-[F]FMeNER-D2., Methods: Whole-body images were acquired for 21 time points in two cynomolgus monkeys for approximately 270 min after injection of radioligand. Compressed 3-D to 2-D planar images were used to identify organs with the highest radiation exposure at each time point. Estimates of the absorbed dose of radiation were calculated using the MIRDOSE 3.1 software program performed with the dynamic bladder and ICRP 30 gastrointestinal tract models., Results: In planar images, peak values of the percent injected dose (%ID) at a time after radioligand injection were calculated for the lungs (26.76% ID at 1.42 min), kidneys (13.55% ID at 2.18 min), whole brain (5.65% ID at 4.48 min), liver (7.20% ID at 2 min), red bone marrow (5.02% ID at 2.06 min), heart (2.36% ID at 1.42 min) and urinary bladder (23% ID at 250 min). Assuming a urine voiding interval of 2.4 h, the four organs with highest exposures in microGy . MBq ( mrad . mCi) were kidneys 126 (468), heart wall 108 (399), lungs 88.4 (327) and urinary bladder 114 (422). The effective doses were estimated with and without urine voiding at a range of 123 (33) and to 131 (35.5) microGy . MBq ( mrad . mCi)., Conclusion: The estimated radiation burden of (S,S)-[F]FMeNER-D2 is comparable to that of other F radioligands.