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See detailMeasuring brain synaptic vesicle protein 2A with positron emission tomography and [18F]UCB-H.
Bahri, Mohamed Ali ULg; Plenevaux, Alain ULg; Aerts, Joël ULg et al

in Alzheimer’s & Dementia: Translational Research & Clinical Interventions (in press)

Introduction: Brain distribution of synaptic vesicle protein 2Awas measured with fluorine-18 UCBH ([18F]UCB-H) and positron emission tomography (PET). Methods: Images of synaptic density were acquired in ... [more ▼]

Introduction: Brain distribution of synaptic vesicle protein 2Awas measured with fluorine-18 UCBH ([18F]UCB-H) and positron emission tomography (PET). Methods: Images of synaptic density were acquired in healthy volunteers (two young participants and two seniors). Input function was measured by arterial blood sampling (arterial input function) and derived from PET images using carotid activity (image-derived input function). Logan graphical analysis was used to estimate regional synaptic vesicle protein 2A distribution volume. Results: [18F]UCB-H uptake was ubiquitous in cortical and subcortical gray matter. Arterial input function and image-derived input function provided regional distribution volume with a high linear relationship. Discussion: The cerebral distribution of [18F]UCB-H is similar to that recently observed with carbon-11 UCB-J ([11C]UCB-J). An accurate [18F]UCB-H quantification can be performed without invasive arterial blood sampling when no suitable reference region is available, using dynamic PET carotid activity. Brain synaptic density can be studied in vivo in normal and pathological aging. [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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See detailEVALUATING THE SPECIFICITY OF [18F]UCB-H FOR THE ISOFORM SV2A, COMPARED WITH ISOFORMS SV2B AND SV2C
Serrano Navacerrada, Maria Elisa ULg; Aerts, Joël ULg; Bahri, Mohamed Ali ULg et al

Poster (2016, November 18)

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 detailEnabling efficient PET imaging of Synaptic Vesicle glycoprotein 2A (SV2A) with a robust and one-step radiosynthesis of a highly potent 18F-labelled ligand ([18F]UCB-H)
Warnier, Corentin ULg; Lemaire, Christian ULg; Becker, Guillaume ULg et al

in Journal of Medicinal Chemistry (2016), 59

We herein describe the straightforward synthesis of a stable pyridyl(4- methoxyphenyl)iodonium salt and its [18F]radiolabelling within a one-step, fully automated and cGMP compliant radiosynthesis of [18F ... [more ▼]

We herein describe the straightforward synthesis of a stable pyridyl(4- methoxyphenyl)iodonium salt and its [18F]radiolabelling within a one-step, fully automated and cGMP compliant radiosynthesis of [18F]UCB-H ([18F]7), a PET tracer for the imaging of Synaptic Vesicle glycoprotein 2A (SV2A). Over the course of one year, 50 automated productions provided 34±2% of injectable [18F]7 from up to 285 GBq (7.7 Ci) of [18F]fluoride in 50 minutes (uncorrected radiochemical yield. Specific Activity = 815±185 GBq/μmol). The successful implementation of our synthetic strategy within routine, high-activity and cGMP productions attests to its practicality and reliability for the production of large doses of [18F]7. In addition to enabling efficient and cost-effective clinical research on a range of neurological pathologies through the imaging of SV2A, this work further demonstrates the real value of iodonium salts for the cGMP 18F-PET tracer manufacturing industry, and their ability to fulfill practical and regulatory requirements in that field. [less ▲]

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See detailDetection of myocardial ischemic memory using 99mTc-fucoidan: preclinical validation
Mikail, N; Louedec, L; Aid, R et al

Conference (2016, June)

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See detailDétection de la mémoire ischémique myocardique par le 99mTc-fucoïdane : validation pré-clinique.
Mikail, N; Louedec, L; Aid, R et al

Conference (2016, May)

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See detailFucoidan: a marine polysaccharide for SPECT diagnosis of thrombosis
Chollet, Lucas; Saboural, Pierre; Rouzet, François et al

in Frontiers (2016, May)

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See detail[18F]UCB-H as a new PET radiotracer for Synaptic vesicle protein 2A: A first clinical trial.
Bahri, Mohamed Ali ULg; Stifkens, M; Bastin, Christine ULg et al

in Tijdschrift voor Nucleaire Geneeskunde (2015, May 09), 37(3), 1457-1458

The 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 ... [more ▼]

The 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, e.g., by the fact that it is a binding site and the primary mechanism of the antiepileptic drug levetiracetam. This drug has recently been suggested to reduce synaptic deficits in a mouse model for Alzheimer’s disease. We here aimed to investigate the cerebral distribution of [18F]UCB-H, which has a high affinity with the SV2A. Dynamic PET data of the head of 4 healthy volunteers were acquired over 100 minutes after injection of 170.4 ± 24.9 MBq of GMP produced [18F]UCB-H. The arterial input function (IF) was obtained by blood sampling but also derived from the dynamic data using the correlation coefficient method. Blood data revealed a consistent amount of [18F]UCB-H in whole blood and plasma indicating 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 image-derived arterial IFs showed to be very similar to the measured ones with a peak-ratio around 0.91 and an area-under-curve ratio about 0.98. The PET images showed a high and rapid uptake of [18F]UCB-H 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. For the three standard compartmental models (1-tissue, 2-tissue, and Logan Plot), similar results were obtained with both the measured and image-derived IFs. Nevertheless 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 (dosimetry has already been reported elsewhere). Image-derived IF showed to be useful for quantitative studies without the need to the arterial blood sampling. This new tracer could help to assess SV2A modifications in neurological pathologies such as Alzheimer’s disease. [less ▲]

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See detailRADIOPHARMACY GMP QC HPLC VALIDATION
Aerts, Joël ULg; Giacomelli, Fabrice ULg; Hubert, Philippe ULg et al

Conference (2015, May 09)

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See detail[18F]UCB-H as a new PET radiotracer for Synaptic vesicle protein 2A: A first clinical trial
Bahri, Mohamed Ali ULg; Stifkens, Mathieu; Bastin, Christine ULg et al

Poster (2015, January 27)

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, e.g., by the fact that it is ... [more ▼]

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, e.g., 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. We here aimed to investigate the cerebral distribution of [18F]UCB-H, which has a high affinity with the SV2A. Dynamic PET data of the head of 4 healthy volunteers were acquired over 100 minutes after injection of 170.4 ± 24.9 MBq of GMP produced [18F]UCB-H. The arterial input function (IF) was obtained by blood sampling. The IF was also derived from the dynamic data using the correlation coefficient method. Blood data revealed a consistent amount of [18F]UCB-H in whole blood and plasma indicating a very low degree of binding of the tracer to the red blood cells. The image-derived arterial IFs were showed to be very similar to the measured ones with a peak-ratio around 0.91 and an area-under-curve ratio about 0.98. 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, 2-tissue, and Logan Plot). The three models gave similar results with both the measured and image-derived IFs. The total distribution volume of the tracer in the brain was greater than 7 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. Image-derived IF showed to be useful for quantitative studies without the need to the arterial blood sampling. SV2A modifications may consequently be assessed in neurological pathologies such as Alzheimer’s disease. [less ▲]

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See detailBiodistribution and radiation dosimetry for the novel SV2A radiotracer [18F]UCB-H: First-in-human study.
Bretin, Florian ULg; Bahri, Mohamed Ali ULg; BERNARD, Claire ULg et al

in Molecular Imaging & Biology (2015), 17

Abstract- [18F]UCB-H is a novel radiotracer with a high affinity for SV2A, a protein expressed in synaptic vesicles. SV2A is the binding site of levetiracetam, a “first in class” antiepileptic drug with a ... [more ▼]

Abstract- [18F]UCB-H is a novel radiotracer with a high affinity for SV2A, a protein expressed in synaptic vesicles. SV2A is the binding site of levetiracetam, a “first in class” antiepileptic drug with a distinct but still poorly understood mechanism of action. The objective of this study was to determine the biodistribution and radiation dosimetry of [18F]UCB-H in a human clinical trial and to establish injection limits according to biomedical research guidelines. Additionally, the clinical radiation dosimetry results were compared to estimations in previously published preclinical data. Dynamic whole body PET/CT imaging was performed over approximately 110 minutes on five healthy male volunteers after injection of 144.5 ± 7.1 MBq (range, 139.1 – 156.5 MBq) of [18F]UCB-H. Major organs were delineated on CT images and time-activity curves were obtained from co-registered dynamic PET emission scans. Time-integrated activity coefficients were calculated as area under the curve using trapezoidal numerical integration. Urinary excretion data based on PET-activities including voiding was simulated using the dynamic bladder module of OLINDA/EXM. The radiation dosimetry was calculated using OLINDA/EXM. The effective dose to the OLINDA/EXM 70 kg standard male was 1.54E-02 ± 6.84E-04 mSv/MBq, with urinary bladder wall, gallbladder wall and the liver receiving the highest absorbed dose. The brain, the tracer’s main organ of interest, received an absorbed dose of 1.89E-02 ± 2.32E-03 mGy/MBq. This first human dosimetry study of [18F]UCB-H indicated that the tracer shows similar radiation burdens to widely used common clinical tracers. Single injections of at maximum 672 MBq for USA practice and 649 MBq for European practice keep radiation exposure below recommended limits. Recently published preclinical dosimetry data extrapolated from mice provided satisfactory prediction of total body and effective dose, but showed significant differences in organ absorbed doses compared to human data. [less ▲]

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See detailGuidance on current good radiopharmacy practice for the small-scale preparation of radiopharmaceuticals using automated modules: a European perspective
Aerts, Joël ULg; Ballinger, james; Behe, Martin et al

in Journal of Labelled Compounds & Radiopharmaceuticals (2014), 57

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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 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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Léonard, Marc ULg; Aerts, Joël ULg; Voccia, Samuel et al

Poster (2013, October 22)

Detailed reference viewed: 126 (20 ULg)