References of "Bahri, Mohamed Ali"
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See detailBrain metabolic dysfunction in Capgras delusion during Alzheimer’s disease: a positron emission tomography study
Jedidi, Haroun ULg; Daury, Noémy; Rémi, Capa et al

in American Journal of Alzheimer's Disease & Other Dementias (in press)

Capgras delusion is characterized by the misidentification of people and by the delusional belief that the misidentified persons have been replaced by impostors, generally perceived as persecutors. Since ... [more ▼]

Capgras delusion is characterized by the misidentification of people and by the delusional belief that the misidentified persons have been replaced by impostors, generally perceived as persecutors. Since little is known regarding the neural correlates of Capgras syndrome, the cerebral metabolic pattern of a patient with probable Alzheimer’s disease (AD) and Capgras syndrome was compared with those of 24 healthy elderly subjects and 26 AD patients without delusional syndrome. Compared to the healthy and AD groups, the patient had significant hypometabolism in frontal and posterior midline structures. In light of current neural models of face perception, our patient’s Capgras syndrome may be related to impaired recognition of a familiar face, subserved by the posterior cingulate/precuneus cortex, and impaired reflection about personally relevant knowledge related to a face, subserved by the dorsomedial prefrontal cortex. [less ▲]

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See detailEvaluation of [18F]UCB-H as a novel PET tracer for synaptic vesicle protein 2A in the brain.
Warnock, Geoffrey; Aerts, Joël ULg; Bahri, Mohamed Ali ULg et al

in Journal of Nuclear Medicine (The) (2014), 55(8), 1336-1341

Synaptic vesicle 2 (SV2) proteins are critical to proper nervous system function and are involved in vesicle trafficking. The SV2A isoform has been identified as the binding site of the antiepileptic ... [more ▼]

Synaptic vesicle 2 (SV2) proteins are critical to proper nervous system function and are involved in vesicle trafficking. The SV2A isoform has been identified as the binding site of the antiepileptic levetiracetam (LEV), making it an interesting therapeutic target for epilepsy. [18F]UCB-H is a novel PET imaging agent with a nanomolar affinity for human SV2A. Methods: preclinical PET studies were carried out in isoflurane anesthetized rats. Arterial input function was measured using an arteriovenous shunt and beta microprobe system. [18F]UCB-H was injected IV (140 ± 20 MBq bolus). Results: brain uptake of [18F]UCB-H was high, matching the expected homogeneous distribution of SV2A. The distribution volume (Vt) for [18F]UCB-H was calculated using Logan’s graphical analysis and the effect of LEV pretreatment on Vt measured. In control animals the mean whole-brain Vt was 9.76 ± 0.52 ml/cm3 (mean ± SD, n=4, test-retest), and the mean reproducibility in test-retest studies was 10.4 ± 6.5 %. Uptake of [18F]UCB-H was dose-dependently blocked by pretreatment with LEV (0.1 - 100 mg/kg IV). Conclusion: our results indicate that [18F]UCB-H is a suitable radiotracer for the imaging of SV2A in vivo. This is the first PET tracer for in vivo quantification of SV2A. The necessary steps for implementation of [18F]UCB-H production under GMP conditions and first in human studies are planned. [less ▲]

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See detail[18F]UCB-H AS A NEW PET RADIOTRACER FOR SYNAPTIC VESICLE PROTEIN 2A
Bahri, Mohamed Ali ULg; Bastin, Christine ULg; Aerts, Joël ULg et al

Poster (2014, June 06)

Synaptic vesicle protein 2A (SV2A) is widely distributed in the brain and has been demonstrated to be involved in vesicle trafficking. The critical role of SV2A in proper nervous system function is shown ... [more ▼]

Synaptic vesicle protein 2A (SV2A) is widely distributed in the brain and has been demonstrated to be involved in vesicle trafficking. The critical role of SV2A in proper nervous system function is shown, for example, by the fact that it is a binding site and the primary mechanism of levetiracetam. Levetiracetam is an antiepileptic drug which has recently been suggested to reduce synaptic deficits in a mouse model for Alzheimer’s disease and to improve cognition in patients with amnestic mild cognitive impairment. We here aimed to investigate the cerebral distribution of [18F]UCB-H, a fluorine-18 radiolabelled PET imaging tracer, which has a high affinity with the SV2A. [18F]UCB-H was radiosynthesized under GMP conditions. Dynamic PET data of the head of four healthy volunteers were acquired over 100 minutes after injection of 170.4 ± 24.9 MBq of [18F]UCB-H. The arterial input function was obtained by blood sampling during the dynamic PET acquisition. The analysis of the blood data reveled a consistent amount of [18F]UCB-H in whole blood and plasma which indicates a very low degree of binding of the tracer to the red blood cells. The unchanged fraction of [18F]UCB-H in plasma showed a bi-exponential behavioral decrease with a starting fraction of 92% of the injected amount of the tracer, measured at 3 min post injection. This fraction decreased to about 50% at 10 min post injection. The [18F]UCB-H PET data showed a high and rapid uptake in the grey matter structures, matching the known ubiquitous distribution of the SV2A in the brain. The kinetics of the tracer in the brain was characterized by an initial high uptake phase followed by rapid washout allowing the standard compartmental modeling (1-tissue compartment, 2-tissue compartment, and Logan graphical analysis). The three models gave consistent results. The two-tissue compartment model fitted the experimental data best and provided a total distribution volume of the [18F]UCB-H in the brain greater than 7 mL/cm3 and a specific distribution volume around 3 mL/cm3. Our results suggest that [18F]UCB-H is a good candidate as radiotracer for brain SV2A proteins and could be used for human studies. In the future, SV2A modifications might be assessed in neurological pathologies such as Alzheimer’s disease. [less ▲]

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See detailExecutive function and grey matter atrophy in healthy aging: A voxel-based morphometry analysis
Manard, Marine ULg; Bahri, Mohamed Ali ULg; Salmon, Eric ULg et al

Poster (2014, June)

Introduction Executive functioning is one of the cognitive domain that declines in healthy aging (Salthouse, Atkinson, & Berish, 2003). In addition, neuroimaging studies pointed out diverse ... [more ▼]

Introduction Executive functioning is one of the cognitive domain that declines in healthy aging (Salthouse, Atkinson, & Berish, 2003). In addition, neuroimaging studies pointed out diverse neurobiological modifications associated to normal aging, such as reduced grey and white matter volumes and cortical thickness (Raz & Rodrigue; 2006). In that context, Voxel Based Morphometry (VBM; Ashburner & Friston, 2000) and Partial Least Square (PLS; McIntoch at al., 1996, 2004) were used to investigate the effect of grey matter atrophy on executive abilities in normal aging. Methods Thirty six young (age range: 18-30) and 43 healthy older (age range: 60-78) adults were included in this study. Executive functioning was assessed by inhibition, updating and shifting tasks (Miyake et al., 2000), and a composite score for general executive ability was created. Structural high resolution T1-weighted images were acquired with a 3T head-only scanner using a standard transmit-receive quadrature head coil (Siemens, Allegra, Erlangen, Germany). The structural images were segmented using VBM8 toolbox, normalized to the MNI stereotaxic space and the resulting grey matter volume images were smoothed (Gaussian kernel: FWHM 8mm). PLS analyses were performed to determine regional grey matter volume differences between young and older adults, and next to identify the regional grey matter volumes specifically associated to executive performance in older participants (p<0.001). PLS is a validated multivariate approach that robustly identifies whole brain activity patterns correlated with behavioral data or experimental design (i.e., scores, conditions or tasks). Results Behavioral data showed a significant age-related decline in executive functioning (t=-5.43; p<.001). MRI analyses showed that significant age-related grey matter volume decrease was mostly observed across a large network including frontal, parietal, and temporal regions. Moreover significant positive correlations between the executive score and the grey matter volumes in older participants were found in a subset of these cortical areas: the inferior, middle and superior frontal cortex, the pre and postcentral gyri, the anterior and middle cingulate cortex, the inferior and superior parietal regions, the retrosplenial cortex, and finally, the inferior, middle and superior temporal regions. Discussion This study first replicated that executive abilities decline with age (Salthouse et al., 2003). This age-related executive decline is related to specific cerebral regions within a large fronto-temporo-parietal network sensitive to age. Interestingly, the areas whose atrophy is linked to executive abilities are quite similar to those evidenced in functional neuroimaging studies in young participants (see Collette & Van der Linden, 2002; Collette, Hogge, Salmon, & Van der Linden, 2006 for reviews). Therefore, using PLS multivariate analyses, we demonstrated that executive changes in normal aging are not dependent on atrophy in frontal areas only but rather comes from a grey matter volume decrease in a large antero-posterior brain network. [less ▲]

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See detail[18F]UCB-H AS A BRAIN SV2A RADIOTRACER: A FIRST CLINICAL TRIAL
Bahri, Mohamed Ali ULg; Bastin, Christine ULg; Aerts, Joël ULg et al

Poster (2014, May 27)

[18F]UCB-H is a fluorine-18 radiolabelled PET imaging tracer with a high affinity for the synaptic vesicle protein 2A (SV2A). This protein, involved in vesicle trafficking and widely distributed in the ... [more ▼]

[18F]UCB-H is a fluorine-18 radiolabelled PET imaging tracer with a high affinity for the synaptic vesicle protein 2A (SV2A). This protein, involved in vesicle trafficking and widely distributed in the brain, represents the binding site and the primary mechanism of the antiepileptic drug levetiracetam. Levetiracetam has recently been suggested to reduce synaptic deficits in a mouse Alzheimer’s disease model and to improve cognition in patients with amnestic mild cognitive impairment, suggesting a possible role for this protein in synaptic integrity. The objective of this study was to investigate the cerebral distribution of [18F]UCB-H in healthy human volunteers. Dynamic PET imaging of the head of four healthy volunteers was performed over 100 minutes after injection of 170.4 ± 24.9 MBq of GMP produced [18F]UCB-H. The input function was acquired by arterial blood sampling during the dynamic PET acquisition. Blood data analysis showed a consistent tracer amount in whole blood and plasma indicating a very low degree of binding of the tracer to the red blood cells. Unchanged [18F]UCB-H fraction in plasma follows a bi-exponential behavioral decrease with a starting fraction of 92% of the injected amount of the tracer, measured at 3 min post injection. This fraction decreases to about 50% at 10 min post injection. The [18F]UCB-H PET data revealed a high and rapid uptake in the grey matter structures, matching the known ubiquitous distribution of SV2A in the brain. The kinetics of the tracer in the brain was characterized by an initial high uptake phase followed by rapid washout allowing the standard compartmental modeling (1-tissue compartment, 2-tissue compartment, and Logan graphical analysis). The three models gave consistent results. The two-tissue compartment model fitted the experimental data best and provided a total distribution volume of [18F]UCB-H in the brain greater than 7 mL/cm3 and a specific distribution volume around 3 mL/cm3. Our results indicate that [18F]UCB-H is a new radiotracer for brain SV2A proteins suitable for human studies. Further studies are warranted to assess SV2A modifications in neurological pathologies such as Alzheimer’s disease. [less ▲]

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See detailQuantitative multi-parameter mapping in parkinson’s disease: preliminary results
Rouillard, Maud ULg; D'Ostilio, Kevin ULg; Albinet, Cedric et al

Poster (2014, May)

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See detailHybrid MicroPET Imaging for Dosimetric Applications in Mice: Improvement of Activity Quantification in Dynamic MicroPET Imaging for Accelerated Dosimetry Applied to 6-[ 18 F] Fluoro- L -DOPA and 2-[ 18 F]Fluoro- L -Tyrosine
Bretin, Florian ULg; Mauxion, T; Warnock, G et al

in Molecular Imaging and Biology (2014), 16(3), 383-394

Purpose: Dynamic microPET imaging has advantages over traditional organ harvesting, but is pronetoquantificationerrorsinsmallvolumes.Hybridimaging,wheremicroPETactivitiesarecross- calibrated using post ... [more ▼]

Purpose: Dynamic microPET imaging has advantages over traditional organ harvesting, but is pronetoquantificationerrorsinsmallvolumes.Hybridimaging,wheremicroPETactivitiesarecross- calibrated using post scan harvested organs, can improve quantification. Organ harvesting, dynamic imaging and hybrid imaging were applied to determine the human and mouse radiation dosimetry of 6-[18 F]fluoro-L-DOPA and 2-[18 F]fluoro-L-tyrosine and compared. Procedures: Two-hour dynamic microPET imaging was performed with both tracers in four separate mice for 18 F-FDOPA and three mice for 18 F-FTYR. Organ harvesting was performed at 2, 5, 10, 30, 60 and 120 min post tracer injection with n=5 at each time point for 18 F-FDOPA and n=3 at each time point for 18 F-FTYR. Human radiation dosimetry projected from animal data was calculated for the three different approaches for each tracer using OLINDA/EXM. S- factors for the MOBY phantom were used to calculate the animal dosimetry. Results: Correlations between dose estimates based on organ harvesting and imaging was improved from r=0.997 to r=0.999 for 18 F-FDOPA and from r=0.985 to r=0.996 (p<0.0001 for all) for 18 F-FTYR by using hybrid imaging. Conclusion: Hybrid imaging yields comparable results to traditional organ harvesting while partially overcoming the limitations of pure imaging. It is an advantageous technique in terms of number of animals needed and labour involved. [less ▲]

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See detailFunctional connectivity and recognition of familiar faces in Alzheimer’s disease
Kurth, Sophie ULg; Bahri, Mohamed Ali ULg; Moyse, Evelyne ULg et al

in Frontiers in Human Neuroscience (2014)

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See detailCognitive and neuroimaging evidence of impaired interaction between Self and memory in Alzheimer’s disease
Genon, Sarah ULg; Bahri, Mohamed Ali ULg; Collette, Fabienne ULg et al

in Cortex : A Journal Devoted to the Study of the Nervous System & Behavior (2014), 51

In human cognition, self and memory processes strongly interact, as evidenced by the memory advantage for self-referential materials (Self Reference Effect (SRE) and Self Reference Recollection Effect ... [more ▼]

In human cognition, self and memory processes strongly interact, as evidenced by the memory advantage for self-referential materials (Self Reference Effect (SRE) and Self Reference Recollection Effect (SRRE)). The current study examined this interaction at the behavioural level and its neural correlates in patients with Alzheimer’s disease (AD). Healthy older controls (HC) and AD patients performed trait-adjectives judgements either for self-relevance or for other-relevance (encoding phase). In a first experiment, the encoding and subsequent yes-no recognition phases were administrated in an MRI scanner. Brain activation as measured by fMRI was examined during self-relevance judgements and anatomical images were used to search for correlation between the memory advantage for self-related items and grey matter density (GMD). In a second experiment, participants described the retrieval experience that had driven their recognition decisions (familiarity vs. recollective experience). The behavioural results revealed that the SRE and SRRE were impaired in AD patients compared to HC participants. Furthermore, verbal reports revealed that the retrieval of self-related information was preferentially associated with the retrieval of contextual details, such as source memory in the HC participants, but less so in the AD patients. Our imaging findings revealed that both groups activated the medial prefrontal cortex (MPFC) at encoding during self-relevance judgments. However, the variable and limited memory advantage for self-related information was associated with GMD in the lateral prefrontal cortex in the AD patients, a region supporting high-order processes linking self and memory. These findings suggest that even if AD patients engage MPFC during self-referential judgments, the retrieval of self-related memories is qualitatively and quantitatively impaired in relation with altered high-order processes in the lateral PFC. [less ▲]

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See detailMetabolic cerebral correlates of conjunctive and relational memory in Alzheimer's disease
Bastin, Christine ULg; Bahri, Mohamed Ali ULg; Collette, Fabienne ULg et al

Poster (2014)

Introduction. Memory deficits are the clinical hallmark of typical Alzheimer’s disease. The precise nature of these deficits however remains to be fully characterized. In this study, we investigated ... [more ▼]

Introduction. Memory deficits are the clinical hallmark of typical Alzheimer’s disease. The precise nature of these deficits however remains to be fully characterized. In this study, we investigated binding in long-term episodic memory. Relational binding processes in memory create an associative link between independent items or between items and context into episodic memories (Cohen et al., 1999). An alternative process, conjunctive binding, allows associations to be encoded as a united representation of features into a single entity (O'Reilly and Rudy, 2001; Mayes et al., 2007). The current study (1) assessed whether Alzheimer’s disease disrupt both conjunctive and relational memory, and (2) related patients’ memory performance to cerebral metabolism. Methods. Thirty patients with mild Alzheimer’s disease and 24 healthy older adults performed a source memory task where items were associated to a background color (Diana et al., 2008, 2010). In one condition, relational binding was promoted by the instruction to associate the item with another object of the same color as the background. In the other condition, color had to be integrated as an item feature (conjunctive binding). Patients’ brain metabolic activity at rest (FDG-PET) was analysed with spatio-temporal Partial Least Squares (McIntosh et al., 1996) in order to assess the relation of behavioral performance and activity in functional cerebral networks. Results. Alzheimer’s disease patients had an impaired capacity to remember item-color associations, with deficits in both relational and conjunctive memory. However, performance in the two kinds of associative memory varied independently across patients. Partial least square analyses revealed a significant pattern of metabolic activity that correlated specifically with each condition (accounting for 76.48 % of the covariance in the data; p< .05). More specifically, poor conjunctive memory was related to hypometabolism in an anterior temporal-posterior fusiform brain network, whereas relational memory correlated with metabolism in regions of the default mode network. Conclusions. These findings support the hypothesis of distinct neural systems specialized in different types of associative memory and point to heterogeneous profiles of memory alteration in Alzheimer’s disease as a function of damage to the respective neural networks. [less ▲]

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See detailA Partial Least Squares Analysis of the self reference effect in Alzheimer's disease: A reply to Irish
Genon, Sarah ULg; Bastin, Christine ULg; Angel, Lucie et al

in Cortex : A Journal Devoted to the Study of the Nervous System & Behavior (2014), 54

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See detailDorsomedial prefrontal metabolism and unawareness of current characteristics of personality traits in Alzheimer’s disease
Jedidi, Haroun ULg; Feyers, Dorothée ULg; Collette, Fabienne ULg et al

in Social Cognitive and Affective Neuroscience (2014)

Anosognosia is a complex symptom corresponding to a lack of awareness of one’s current clinical status. Anosognosia for cognitive deficits has frequently been described in Alzheimer’s disease (AD), while ... [more ▼]

Anosognosia is a complex symptom corresponding to a lack of awareness of one’s current clinical status. Anosognosia for cognitive deficits has frequently been described in Alzheimer’s disease (AD), while unawareness of current characteristics of personality traits has rarely been considered. We used a well-established questionnaire-based method in a group of 37 AD patients and in healthy controls to probe self- and hetero-evaluation of patients’ personality and we calculated differential scores between each participant’s and his/her relative’s judgments. A brain-behavior correlation was performed using FDG-PET images. The behavioral data showed that AD patients presented with anosognosia for current characteristics of their personality and their anosognosia was primarily explained by impaired third perspective taking. The brain-behavior correlation analysis revealed a negative relationship between anosognosia for current characteristics of personality and dorsomedial prefrontal cortex (dMPFC) activity. Behavioral and neuroimaging data are consistent with the view that impairment of different functions subserved by the dMPFC (self-evaluation, inferences regarding complex enduring dispositions of self and others, confrontation of perspectives in interpersonal scripts) plays a role in anosognosia for current characteristics of personality in AD patients. [less ▲]

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See detailPLS analysis of fMRI data on cognitive processes
Bahri, Mohamed Ali ULg; Genon, Sarah ULg; Bastin, Christine ULg et al

Conference (2013, December 12)

Cognitive processes like memory and self-referential are known to be underlined by extended neural networks. To study these complex processes, multivariate methods appear as the methods of the first ... [more ▼]

Cognitive processes like memory and self-referential are known to be underlined by extended neural networks. To study these complex processes, multivariate methods appear as the methods of the first choice since they take into account the functional integration. Partial Least Square (PLS) was used to study neural networks related to memory and self-referential processing in Alzheimer’s disease patients (AD) and two examples were presented. In the first one, we investigated the metabolic correlates of two forms of memory (conjunctive and relational memory performances) in AD. PLS identified two different brain networks highlighting correlations of the two types of memory and the glucose metabolism. In the second example, we assessed brain regions engaged during self-referential processing of information in AD patients during a task related fMRI study. PLS identified a wide brain network showing the effect of self- vs. other-referential processing. In contrast to univariate methods, PLS showed to be suitable for the study of cognitive processes. [less ▲]

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See detailPerformance evaluation and X-ray dose quantification for various scanning protocols of the GE eXplore 120 micro-CT
Bretin, Florian ULg; Warnock, Geoffrey; Luxen, André ULg et al

in IEEE Transactions on Nuclear Science (2013), 60(5), 3235-3241

The aim of this study was to evaluate the performance of the General Electric eXplore 120 micro-CT regarding image quality and delivered dose of several protocols. Image quality (resolution, linearity ... [more ▼]

The aim of this study was to evaluate the performance of the General Electric eXplore 120 micro-CT regarding image quality and delivered dose of several protocols. Image quality (resolution, linearity, uniformity and geometric accuracy) was assessed using the vmCT phantom developed for the GE eXplore Ultra, the QRM low contrast and the QRM Bar Pattern Phantom. All dose measurements were performed using a mobileMOSFET dose verification system and the CTDI100 and the MSAD were determined with a custom built PMMA phantom. Additionally, in vivo scans in sacrificed rats with different weights were acquired to assess dose, contrast and resolution variation due to X-ray absorption in surrounding tissue. The spatial resolution was determined as between 95 and 138 μm with a geometric accuracy of 0.1%. The system has a highly linear response to the iodine concentrations (0.937 to 30 mg/ml) for all protocols. The calculated CTDI100 ranged from 20.15 to 56.79 mGy and the MSAD from 27.98 to 77.45 mGy. The results were confirmed by in vivo scans in rats with different weights and no impact of body weight on delivered dose could be observed. However, body weight had a slight impact on image contrast and resolution. [less ▲]

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See detailIn vivo PET/CT in a human glioblastoma chicken chorioallantoic membrane model: A new tool for oncology and radiotracer development.
Warnock, Geoffrey; Turtoi, Andrei ULg; Blomme, Arnaud ULg et al

in Journal of Nuclear Medicine : Official Publication, Society of Nuclear Medicine (2013), 54(10), 1782-1788

For many years the laboratory mouse has been used as the standard model for in vivo oncology research, particularly in the development of novel PET tracers, but the growth of tumors on chicken ... [more ▼]

For many years the laboratory mouse has been used as the standard model for in vivo oncology research, particularly in the development of novel PET tracers, but the growth of tumors on chicken chorioallantoic membrane (CAM) provides a more rapid, low cost and ethically sustainable alternative. For the first time, we demonstrate the feasibility of in vivo PET and CT imaging in a U87 glioblastoma tumor model on chicken chorioallantoic membrane (CAM), with the aim of applying this model for screening of novel PET tracers. Methods: U87 glioblastoma cells were implanted on the CAM at day 11 post-fertilization and imaged at day 18. A small animal imaging cell was used to maintain incubation and allow anesthesia using isoflurane. Radiotracers were injected directly into the exposed CAM vasculature. Sodium [18F]fluoride was used to validate the imaging protocol, demonstrating that image-degrading motion can be removed with anesthesia. Tumor glucose metabolism was imaged using [18F]fluorodeoxyglucose and tumor protein synthesis was imaged using 2-[18F]fluoro-L-tyrosine. Anatomical images were obtained by contrast enhanced CT, facilitating clear delineation of the tumor, delineation of tracer uptake in tumor versus embryo and accurate volume measurements. Results: PET imaging of tumor glucose metabolism and protein synthesis was successfully demonstrated in the CAM U87 glioblastoma model. Catheterization of CAM blood vessels facilitated dynamic imaging of glucose metabolism with [18F]fluorodeoxyglucose and demonstrated the ability to study PET tracer uptake over time in individual tumors, while CT imaging improved the accuracy of tumor volume measurements. Conclusion: In summary, we describe the novel application of PET/CT in the CAM tumor model, with optimization of typical imaging protocols. PET imaging in this valuable tumor model could prove particularly useful for rapid, high-throughput screening of novel radiotracers. [less ▲]

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