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See detailPharmacokinetic characterization of [18F]UCB-H PET radiopharmaceutical in the rat brain.
Becker, Guillaume ULg; Warnier, Corentin; Serrano Navacerrada, Maria Elisa ULg et al

in Molecular Pharmaceutics (in press)

The synaptic vesicle glycoprotein 2A (SV2A), a protein essential to the proper nervous system function, is found in presynaptic vesicles. Thus, SV2A targeting, using dedicated radiotracers combined with ... [more ▼]

The synaptic vesicle glycoprotein 2A (SV2A), a protein essential to the proper nervous system function, is found in presynaptic vesicles. Thus, SV2A targeting, using dedicated radiotracers combined with positron emission tomography (PET), allows the assessment of synaptic density in the living brain. The first-in-class fluorinated SV2A specific radioligand, [18F]UCB-H, is now available at high-activity through an efficient radiosynthesis compliant with the current good manufacturing practices (cGMP). We report here a non-invasive method to quantify [18F]UCB-H binding in rat brain with microPET. Validation study in rats confirmed the need of high enantiomeric purity to target SV2A in vivo. We demonstrated the reliability of a population-based input function to quantify SV2A in preclinical microPET setting. Finally, we investigated the in vivo metabolism of [18F]UCB-H and confirmed the negligible amount of radiometabolites in the rat brain. Hence, the in vivo quantification of SV2A using [18F]UCB-H microPET seems a promising tool for the assessment of the synaptic density in the rat brain, and opens the way for longitudinal follow-up in neurodegenerative diseases rodents’ models. [less ▲]

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See detailSelf in Dementia
Antoine, Nicolas ULg; Genon, Sarah ULg; Bastin, Christine ULg et al

in Mishara; Corlett, P.; Fletcher, P. (Eds.) et al Phenomenological Neuropsychiatry, How Patient Experience Bridges Clinic with Clinical Neuroscience (in press)

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See detailExploration des processus de recollection et de familiarité chez des patients présentant une plainte mnésique : Une étude longitudinale
Simon, Jessica ULg; Collette, Fabienne ULg; Salmon, Eric ULg et al

Poster (2017, June 01)

Les données actuelles suggèrent une altération précoce de la recollection dans les premiers stades de la maladie d’Alzheimer. Par contre, aucun consensus n’a pu être dégagé concernant l’intégrité de la ... [more ▼]

Les données actuelles suggèrent une altération précoce de la recollection dans les premiers stades de la maladie d’Alzheimer. Par contre, aucun consensus n’a pu être dégagé concernant l’intégrité de la familiarité. En effet, certaines études suggèrent une altération précoce de ce processus, alors que d’autres montrent une préservation de celle-ci. Dans ce cadre, nous avons exploré l'impact du type de format de reconnaissance et du matériel sur la recollection et la familiarité chez des patients qui se plaignent de leur mémoire. Nous avons recruté 23 participants âgés contrôles, 9 patients présentant un trouble subjectif de la mémoire (SCI) et 23 patients présentant un trouble cognitif léger (TCL). Les participants ont réalisé une tâche de reconnaissance à choix forcé à deux alternatives et une tâche de reconnaissance Oui-Non incluant des images et des mots. Ces tâches étaient suivies d’une courte évaluation neuropsychologique. Quinze participants âgés contrôles et 23 patients ont participé au suivi, incluant une évaluation neuropsychologique, dans un délai moyen de 21 mois. Nos résultats montrent qu’à l’inclusion, les patients avec TCL avaient des performances moindres en reconnaissance que les deux autres groupes, qui ne différaient pas. De même, ces patients utilisaient moins efficacement la recollection et la familiarité par rapport aux contrôles et aux SCI, qui présentaient des performances similaires. Il n’y avait aucune interaction entre le groupe et le type de format ou le matériel. Lors du suivi, cinq patients avec TCL ont retrouvé un niveau d’efficience cognitive dans la norme et ont été considérés comme des SCI car les plaintes mnésiques étaient toujours présentes. Sur la base de l'adaptation française du test de rappel libre et indicé (RLRI-16), nous avons calculé une pente de déclin mnésique pour chacun de nos patients. Nous avons observé que les indices de recollection et de familiarité étaient expliqués par les pentes de déclin calculées sur le nombre total d’items rappelés librement. Ainsi, nous avons observé un déclin de la recollection et la familiarité dans le groupe de TCL mais pas dans celui des SCI, bien que les deux groupes se plaignent de leur mémoire. En outre, l'efficacité de la familiarité pourrait prédire un déclin cognitif futur. [less ▲]

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See detailRecognition memory is associated with hippocampal volume in aging population: new evidence from brain imaging study
Narbutas, Justinas ULg; Blanpain, Manon ULg; Van Egroo, Maxime ULg et al

Poster (2017, May 31)

Introduction. The hippocampus is crucial for episodic memory, especially for recollection and pattern separation (i.e., the ability to store similar episodes as distinct memory traces). Episodic memory ... [more ▼]

Introduction. The hippocampus is crucial for episodic memory, especially for recollection and pattern separation (i.e., the ability to store similar episodes as distinct memory traces). Episodic memory declines with aging and this has been associated with hippocampal dysfunction. The main objective of our study was to explore how performance on a recognition memory task designed to assess pattern separation is associated with hippocampal volume in aging population. Method. Fourteen healthy late middle-aged participants (52-69 years-old) were evaluated on a Mnemonic Similarity Task (MST). In this task, participants study pictures and then have to discriminate between targets, similar lures, and unrelated foil objects. Recognition memory (RM) is assessed as the difference between hits and false alarms to unrelated foils, while pattern separation Bias metric (BPS) is the difference between the rate of ‘‘Similar’’ responses given to the lure items minus ‘‘Similar’’ responses given to the foils. Hippocampal volume was calculated using ASHS software, which uses T1-weighted and T2-weighted MRI to obtain optimal segmentation of hippocampal subfields. Results. Correlation analysis of preliminary data revealed that RM was significantly positively associated with the volume of the left subiculum and left perirhinal area 35. BPS was positively correlated with the volume of right CA2 region, but negatively associated with the volume of right CA3 region. Discussion. In a late middle-aged population, better visual recognition memory is associated with larger volume of the left subiculum and perirhinal area 35, two regions supporting representation of objects. [less ▲]

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See detailRecognition memory is associated with hippocampal volume in aging population: new evidence from brain imaging study
Narbutas, Justinas ULg; Blanpain, Manon ULg; Van Egroo, Maxime ULg et al

Poster (2017, May 19)

Introduction. The hippocampus is crucial for episodic memory, especially for recollection and pattern separation (i.e., the ability to store similar episodes as distinct memory traces). Episodic memory ... [more ▼]

Introduction. The hippocampus is crucial for episodic memory, especially for recollection and pattern separation (i.e., the ability to store similar episodes as distinct memory traces). Episodic memory declines with aging and this has been associated with hippocampal dysfunction. The main objective of our study was to explore how performance on a recognition memory task designed to assess pattern separation is associated with hippocampal volume in aging population. Method. Fourteen healthy late middle-aged participants (52-69 years-old) were evaluated on a Mnemonic Similarity Task (MST). In this task, participants study pictures and then have to discriminate between targets, similar lures, and unrelated foil objects. Recognition memory (RM) is assessed as the difference between hits and false alarms to unrelated foils, while pattern separation Bias metric (BPS) is the difference between the rate of ‘‘Similar’’ responses given to the lure items minus ‘‘Similar’’ responses given to the foils. Hippocampal volume was calculated using ASHS software, which uses T1-weighted and T2-weighted MRI to obtain optimal segmentation of hippocampal subfields. Results. Correlation analysis of preliminary data revealed that RM was significantly positively associated with the volume of the left subiculum and left perirhinal area 35. BPS was positively correlated with the volume of right CA2 region, but negatively associated with the volume of right CA3 region. Discussion. In a late middle-aged population, better visual recognition memory is associated with larger volume of the left subiculum and perirhinal area 35, two regions supporting representation of objects. [less ▲]

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See detailRecollection versus familiarité dans le vieillissement normal et pathologique : Impact du format du test
Simon, Jessica ULg; Gilsoul, Jessica ULg; SALMON, Eric ULg et al

Poster (2017, May 19)

If familiarity is better preserved than recollection in aging and in the early stage of Alzheimer's disease (Koen & Yonelinas, 2014), the experimental conditions promoting its use should be beneficial to ... [more ▼]

If familiarity is better preserved than recollection in aging and in the early stage of Alzheimer's disease (Koen & Yonelinas, 2014), the experimental conditions promoting its use should be beneficial to these populations. One condition influencing the relative contribution of recollection and familiarity during recognition is the format of the test. The aim of this study was to investigate the impact of test format on recollection and familiarity in normal aging and in MCI in two tasks where the level of performance is equalized. Seventy young participants, 70 younger-old (55-69 years old), 69 older-old (70-85 years old), and 13 MCIs were presented with forced-choice and yes/no visual recognition memory tasks with the Remember/Know/ Guess paradigm. Young participants had better recognition memory performance than younger-old, who performed better than older-old and MCIs. Recollection and familiarity declined progressively in healthy aging. In MCI, recollection was more affected than familiarity, but patients demonstrated a more liberal use of familiarity. Finally, test format did not influence strongly the results. Young people used recollection more often in the forced-choice task compared to the yes/no task. [less ▲]

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See detailExploration des processus de recollection et de familiarité chez des patients présentant une plainte mnésique : une étude longitudinale
Simon, Jessica ULg; Collette, Fabienne ULg; SALMON, Eric ULg et al

Poster (2017, May 19)

Recollection refers to recall of details about past events, and familiarity is a feeling of oldness. In this study, we tested how recollection and familiarity are affected in patients with memory ... [more ▼]

Recollection refers to recall of details about past events, and familiarity is a feeling of oldness. In this study, we tested how recollection and familiarity are affected in patients with memory complaints compared to normal aging. We recruited 23 healthy older participants, 9 patients with subjective memory impairment (SCI) and 23 patients with mild cognitive impairment (MCI). Participants performed one 2-alternative forced-choice and one Yes-No recognition memory task including pictures and words, followed by a short neuropsychological evaluation. Fifteen healthy participants and 23 patients (9 SCI and 14 MCI) took part in a neuropsychological follow-up after a mean delay of 21 months. At inclusion, MCI patients had poorer performance in recognition than the other groups, which did not differ. MCI patients had worse performance regarding familiarity and recollection indexes compared to healthy controls and SCI, who exhibit similar performance. There was no interaction between groups and format or material. During the follow-up evaluation, five MCI returned to a normal level of efficiency and were considered as SCI. Based on the French adaptation of the free and cued selective reminding test (RLRI-16), we calculated cognitive decline curves in our patients. We observed that recollection and familiarity indexes were explained by the decline curves calculated on the number of freely recalled items. So, recollection and familiarity were used less efficiently in MCI than SCI although both groups complained about their memory. [less ▲]

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See detailRecollection versus familiarity in normal aging and in mild cognitive impairment: Impact of test format
Simon, Jessica ULg; Gilsoul, Jessica ULg; SALMON, Eric ULg et al

Poster (2017, March 24)

If familiarity is better preserved than recollection in aging and in the early stage of Alzheimer's disease (Koen & Yonelinas, 2014), the experimental conditions promoting its use should be beneficial to ... [more ▼]

If familiarity is better preserved than recollection in aging and in the early stage of Alzheimer's disease (Koen & Yonelinas, 2014), the experimental conditions promoting its use should be beneficial to these populations. One condition influencing the relative contribution of recollection and familiarity during recognition is the format of the test. The aim of this study was to investigate the impact of test format on recollection and familiarity in normal aging and in MCI in two tasks where the level of performance is equalized. Seventy young participants, 70 younger-old (55-69 years old), 69 older-old (70-85 years old), and 13 MCIs were presented with forced-choice and yes/no visual recognition memory tasks with the Remember/Know/ Guess paradigm. Young participants had better recognition memory performance than younger-old, who performed better than older-old and MCIs. Recollection and familiarity declined progressively in healthy aging. In MCI, recollection was more affected than familiarity, but patients demonstrated a more liberal use of familiarity. Finally, test format did not influence strongly the results. Young people used recollection more often in the forced-choice task compared to the yes/no task. [less ▲]

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See detailAnosognosia for behavioral disorder is related to confidence for false self-related memories in Alzheimer’s disease
Mélon, Marlène; Collette, Fabienne ULg; Salmon, Eric ULg et al

Poster (2017, March 24)

Impaired self-awareness (i.e. anosognosia) and altered metacognitive monitoring in memory tasks have both been evidenced in AD. Furthermore, cognitive studies showed disrupted interaction between self and ... [more ▼]

Impaired self-awareness (i.e. anosognosia) and altered metacognitive monitoring in memory tasks have both been evidenced in AD. Furthermore, cognitive studies showed disrupted interaction between self and memory cognitive systems in AD, reducing cognitive advantages of self-related memories (i.e. decreasing self reference effect, SRE) in these patients. However, how anosognosia relates to impaired metacognitive monitoring in AD, particularly for self-related memories, is still an open question. To investigate this question, an ecological memory task based on face-name associations was administrated to 20 healthy older controls (HC) and 20 mild AD patients. The influence of self-reference at encoding was assessed on subsequent name recall and recollective experience, as well as on predictive (feeling-of-knowing, FOK) and postretrieval (judgments-of-confidence, JOC) metacognitive judgments on name recognition in all participants. Furthermore relationships between metacognitive outcomes and awareness of daily cognitive and behavioral impairment was examined in AD. Altered SRE was evidenced in name recall and recollective experience in AD. Patients also showed impaired FOK and JOC, as well as lower awareness of their daily functioning impairment (anosognosia). Nevertheless, differential effect of self on metacognitive judgment in AD and HC was only observed on JOC for false memories. Importantly, anosognosia for behavioral disorders was related to post-retrieval confidence for false recognition of self-related items in AD patients. Thus, anosognosia concerning behavioral disorder and altered post-retrieval monitoring of self-related memories appear to be related in AD. We hypothesized that impaired monitoring of personal false memories may lead AD patients to rely on distorted recent reality when providing judgment about their everyday behavioral functioning. [less ▲]

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See detailRelating pessimistic memory predictions to Alzheimer’s disease brain structure
Genon, Sarah ULg; Simon, Jessica ULg; Bahri, Mohamed Ali ULg et al

Poster (2017, March 23)

Patients with Alzheimer’s disease (AD) show impairment of episodic memory and related metacognitive processes. The present study examined subjective metacognitive judgments preceding objective memory ... [more ▼]

Patients with Alzheimer’s disease (AD) show impairment of episodic memory and related metacognitive processes. The present study examined subjective metacognitive judgments preceding objective memory retrieval and investigated the neural correlates of pessimistic predictions for successfully retrieved memories in AD patients. AD patients and healthy older participants provided predictive judgements on their recognition performance before retrieval of famous (semantic) and recently learned (episodic) names. Correlations between grey matter volume (GMV) in T1 images and behavioural scores were examined with multivariate (PLS) and univariate (GLM) analyses in AD patients. AD patients showed a significant proportion of successful name recognition preceded by pessimistic prediction (Prediction_low_hits) in episodic memory. PLS revealed that behavioural pattern in AD patients was related with a mainly right lateralized pattern of GMV decrease including medial temporal lobe and posterior cingulate cortex, but also right ventrolateral prefrontal cortex (VLPFC). GLM further confirmed that pessimistic prediction negatively correlated with GMV in VLPFC. Thus, impaired monitoring processes (possibly influenced by inaccurate beliefs) allowing inferences about one’s own memory performance are primarily related to decrease GMV in VLPFC in AD patients. [less ▲]

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See detailRecognition memory is associated with hippocampal volume in aging population: new evidence from brain imaging study
Narbutas, Justinas ULg; Blanpain, Manon ULg; Van Egroo, Maxime ULg et al

Poster (2017, March 23)

Introduction. The hippocampus is crucial for episodic memory, especially for recollection and pattern separation (i.e., the ability to store similar episodes as distinct memory traces). Episodic memory ... [more ▼]

Introduction. The hippocampus is crucial for episodic memory, especially for recollection and pattern separation (i.e., the ability to store similar episodes as distinct memory traces). Episodic memory declines with aging and this has been associated with hippocampal dysfunction. The main objective of our study was to explore how performance on a recognition memory task designed to assess pattern separation is associated with hippocampal volume in aging population. Methods. Fourteen healthy late middle-aged participants (52-69 years-old) were evaluated on a Mnemonic Similarity Task (MST). In this task, participants study pictures and then have to discriminate between targets, similar lures, and unrelated foil objects. Recognition memory (RM) is assessed as the difference between hits and false alarms to unrelated foils, while pattern separation Bias metric (BPS) is the difference between the rate of ‘‘Similar’’ responses given to the lure items minus ‘‘Similar’’ responses given to the foils. Hippocampal volume was calculated using ASHS software, which uses T1-weighted and T2-weighted MRI to obtain optimal segmentation of hippocampal subfields. Results. Correlation analysis of preliminary data revealed that RM was significantly positively associated with the volume of the left subiculum and left perirhinal area 35, while there were no significant correlations in the right hemisphere. BPS was positively correlated with the volume of right CA2 region, but negatively associated with the volume of right CA3 region, what is more contradictory according to the current literature. No significant link was found between BPS and the volume of hippocampal subfields in the left hemisphere. Conclusion. In a middle-aged population, better visual recognition memory is associated with larger volume of the left subiculum and perirhinal area 35, two regions supporting representation of objects [less ▲]

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See detailNeural correlates of subsequent recollection and familiarity in ageing
François, Sarah ULg; Angel, Lucie; Salmon, Eric ULg et al

Poster (2017, March)

It is now commonly accepted that, in ageing, recollection processes are impaired and familiarity seems to be relatively preserved. In this study, we were interested in the differences between younger and ... [more ▼]

It is now commonly accepted that, in ageing, recollection processes are impaired and familiarity seems to be relatively preserved. In this study, we were interested in the differences between younger and older participants regarding cerebral activity during encoding depending on whether the item later elicited recollection or familiarity. Twenty young volunteers and 19 older volunteers were presented visual stimuli depicting objects. After a first fMRI session in which the items were encoded, they underwent a recognition memory task in which they judged whether items were Remembered, Familiar or New. Data were analysed using SPM8, with an event-related design comparing modifications in cerebral activity between the two subjects groups during encoding (1) for the items leading to recollection compared to those leading to familiarity, and (2) for the items associated with familiarity compared to those which were not recognized. Results showed that older adults displayed a heightened activity in regions of the default-mode network for subsequent recollection. As it does not appear to be deleterious, it could stem from a more frequent use of self-referential appraisal as an encoding strategy in older adults. Furthermore, they show supplementary contralateral activations in frontal and temporal regions, which could be indicative of dedifferentiation or attempted compensation. To conclude, it appears that despite relying less on elaborative encoding, older adults seem to be able to perform recollection using qualitatively different strategies than young adults. [less ▲]

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See detailEvaluating the specificity of [18F] UCB-H for the isoform SV2A, compared with isoforms SV2B and SV2C
Serrano Navacerrada, Maria Elisa ULg; Becker, Guillaume ULg; Bahri, Mohamed Ali ULg et al

Poster (2017, February 01)

Background: SV2A is the most studied isoform of the Synaptic Vesicle 2 proteins, which are involved in the synaptic vesicle trafficking, being important in normal and pathological process, like the ... [more ▼]

Background: SV2A is the most studied isoform of the Synaptic Vesicle 2 proteins, which are involved in the synaptic vesicle trafficking, being important in normal and pathological process, like the epilepsy (1, 2). [18F]UCB-H was developed like a tool to study the role of this isoform with neuroimaging techniques (3, 4). The objective of this study was to evaluate its specificity to this isoform comparing with the others, through a competition assay in rats with ex-vivo autoradiography and mPET imaging. Methods: Forty male Sprague-Dawley were used in ex-vivo autoradiography experiments (N=20) and in microPET imaging (N=20). Animals were pre-treated 30 minutes before the injection of [18F]UCB-H with a dose IP either of vehicle, Keppra (SV2A ligand), UCB068 (SV2B ligand) or UCB054 (SV2C ligand). Ex-vivo autoradiography was carried out 5 minutes after radiotracer injection while mPET images were acquiring with a dynamic scanner of 1 hour. Data were expressed in Standard Uptake Value and then, the area under the curve was calculated for the total process. Results: In ex-vivo autoradiography, ANOVA of two-ways showed statistical significant differences in brain uptake of [18F]UCB-H among the groups pretreated with Keppra or the ligand for SV2B and the control group. Regarding mPET data, statistical significant differences were found between the group injected with keppra and the rest of groups. Conclusion: Even if a considerable affinity between the ligands UCB068 and UCB054, and the receptor for the isoform SV2A exists, it is only detected during the first 5 minutes (ex-vivo technique), being certainly due to a nonspecific binding. This binding is not strong enough to show a direct competition with the radiotracer during a mPET acquisition. These results allow us to conclude that [18F]UCB-H is a suitable radiotracer for the imaging of the isoform SV2A in vivo, allowing us the clinical study about the molecular base of a disease with a high population impact, like the epilepsy. [less ▲]

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See detailIN VIVO STUDY OF THE SV2A PROTEIN IN THE KAINIC ACID EPILEPSY RAT MODEL
Serrano Navacerrada, Maria Elisa ULg; Becker, Guillaume ULg; Bahri, Mohamed Ali ULg et al

Poster (2017)

Introduction Epilepsy is one of the commonest neurological disorders [1]. Antiepileptic drugs mainly target the SV2A protein [2] but its actual role is still largely unknown. [18F]UCB-H was developed to ... [more ▼]

Introduction Epilepsy is one of the commonest neurological disorders [1]. Antiepileptic drugs mainly target the SV2A protein [2] but its actual role is still largely unknown. [18F]UCB-H was developed to study in vivo SV2A brain proteins [3, 4]. The present pilot study was undertaken to evaluate for the first time in vivo in rats SV2A expression in the Kaïnic Acid (KA) epilepsy model [5]. Although this model is well studied in mice, few reports were devoted to rats. Imaging-wise, rats are very interesting thanks to a bigger brain size (reduction of the partial volume effect). Methods Three male Sprague-Dawley were used, one injected with saline and two with multiple KA injections (3 x 5mg/kg) [6]. 75 days later, when spontaneous seizures started to appear, microPET (Focus 120 ) was performed under isoflurane anesthesia (2.5-3 % in air) for 1 hour with [18F]UCB-H (41 ± 5 MBq IV tail vein) followed by MRI (9.4T Agilent, anatomical T2). Coregistration was done with PMOD 3.6 software. Data were expressed as SUV and areas under the curve were calculated for the different regions. Results [18F]UCB-H microPET images showed an important reduction (20-30%) for SV2A after KA injections mainly localized in amygdala, hippocampus, lateral parietal association cortex and cingulate cortex. The rest of the brain was globally unchanged. MRI revealed atrophy and inflammation in amygdala and hippocampus. Conclusions These preliminary results obtained in KA treated rats showed that [18F]UCB-H was able to detect important modifications for SV2A in relevant regions for epilepsy and appears as a valuable tool to follow in vivo SV2A through longitudinal studies. KA model in rats deserves for further development and validation as a tool for the study of epilepsy. [less ▲]

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See detailIN VIVO STUDY OF THE SV2A PROTEIN IN AN EPILEPTIC RAT MODEL
Serrano Navacerrada, Maria Elisa ULg; Becker, Guillaume ULg; Bahri, Mohamed Ali ULg et al

Poster (2017)

Introduction Epilepsy is one of the commonest neurological disorders, affecting more than 60 million people worldwide [1]. New and effective antiepileptic drugs mainly target the SV2A protein [2] but its ... [more ▼]

Introduction Epilepsy is one of the commonest neurological disorders, affecting more than 60 million people worldwide [1]. New and effective antiepileptic drugs mainly target the SV2A protein [2] but its actual role is still largely unknown. [18F]UCB-H was developed as a tool to study in vivo the brain expression of this isoform [3, 4]. Due to the fact that only post-mortem studies were reported so far [5] the present pilot study was undertaken in order to evaluate for the first time in vivo in rats the SV2A expression in the validated Kaïnic Acid (KA) epilepsy model [6]. Methods Three male Sprague-Dawley were used, one injected with saline (Sham) and two with multiple KA systemic injections (5mg/kg x 3) [9]. SV2A brain levels were estimated at day 75, when spontaneous seizures started to appear. Animals were anesthetized (2.5 to 3 % isoflurane), and scanned for 1 hour with [18F]UCB-H (41 ± 5 MBq IV tail vein) in a Focus 120 microPET system and with MRI (9.4T Agilent, anatomical T2). Coregistration was done with PMOD 3.6 software. Data were expressed in SUV and areas under the curve were calculated for the different regions. Results [18F]UCB-H microPET images showed an important reduction (20-30%) for SV2A after KA injections mainly localized in amygdala, hippocampus, lateral parietal association cortex and cingulate cortex. The rest of the brain was globally unchanged. MRI revealed atrophy and inflammation in amygdala and hippocampus. Conclusions These preliminary results in KA treated rats presenting spontaneous seizures showed that [18F]UCB-H microPET was able to detect important reductions for the SV2A proteins in relevant regions for epilepsy [5]. Accordingly to this, we can infer that the KA model in rats deserves for further development and validation as a tool for the study of epilepsy. [18F]UCB-H appears as a valuable tool to follow in vivo SV2A proteins through longitudinal protocols and in turn to better understand its actual role in epilepsy. References/acknowledgements This work was funded by University of Liège, F.R.S.-FNRS, Walloon Region and UCB Pharma. Alain Plenevaux is research director from F.R.S.-FNRS. [1] Alexopoulos, Epileptology, 2004 [2] Hamann et al., Eur J Pharmacol, 2008 [3] Bretin et al., Molecular Imaging and Biology, 2015 [4] Warnock et al., J Nucl Med., 2014 [5] Wang et al., J Mol Neurosci., 2014 [6] Hellier et al., Epilepsy Res., 1998 [less ▲]

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See detail[18F]UCB-H RADIOTRACER AS A TOOL TO UNDERSTAND THE ROLE OF THE SV2A PROTEIN
Serrano Navacerrada, Maria Elisa ULg; Becker, Guillaume ULg; Bahri, Mohamed Ali ULg et al

Poster (2017)

Background: SV2A is the most studied isoform of the Synaptic Vesicle 2 proteins, which are involved in the synaptic vesicle trafficking, being important both in normal as in pathological process (1, 2 ... [more ▼]

Background: SV2A is the most studied isoform of the Synaptic Vesicle 2 proteins, which are involved in the synaptic vesicle trafficking, being important both in normal as in pathological process (1, 2). Until now, only one study in vivo has been reported, showing a reduction of SV2A levels in the epilepsy (3). [18F]UCB-H was developed like a current tool to study the role of SV2A with in vivo techniques (4, 5), and as a tool in clinical investigations. The objective of this research was to evaluate the radiotracer specificity to this isoform comparing with the others, through a competition assay in rats with ex-vivo autoradiography and mPET imaging. Methods: Forty male Sprague-Dawley were used in ex-vivo autoradiography experiments (N=20) and in microPET imaging (N=20). Animals were pre-treated 30 minutes before the injection of [18F]UCB-H with a dose IP either of vehicle, Keppra (SV2A ligand), UCB068 (SV2B ligand) or UCB054 (SV2C ligand). Ex-vivo autoradiography was carried out 5 minutes after radiotracer injection while mPET images were acquiring with a dynamic scanner of 1 hour. Standard Uptake Value (SUV) and Distribution Volume (VT) were calculated and the correlation between both parameters was determined. Results: In ex-vivo autoradiography, ANOVA of two-ways showed statistical significant differences in brain uptake of [18F]UCB-H among the groups pretreated with Keppra or the ligand for SV2B and the control group. Regarding mPET data, statistical significant differences were found between the group injected with keppra and the rest of groups. Pearson Correlation between SUV and VT was strong, with a value of 0.955. Conclusion: Even if a considerable affinity between the ligands UCB068 and UCB054, and the receptor for the isoform SV2A exists, it is only detected during the first 5 minutes (ex-vivo technique), being certainly due to a nonspecific binding. This binding is not strong enough to show a direct competition with the radiotracer during a mPET acquisition. These results allow us to conclude that [18F]UCB-H is a suitable radiotracer for the imaging of the isoform SV2A in vivo, allowing us the clinical study about the molecular base of a disease with a high population impact, like the epilepsy. 1) Van Vliet et al., 2009. Epilepsia 2) Crèvecœur et al., 2013. BMC Neurosci. 3) Finnema et al., 2016; Sci Transl Med. 4) Bretin et al., 2013.EJNMMI Res 5) Bretin et al., 2015.Mol Imaging Biol [less ▲]

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