References of "Lemaire, Christian"
     in
Bookmark and Share    
Full Text
Peer Reviewed
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 ▲]

Detailed reference viewed: 70 (25 ULg)
Full Text
Peer Reviewed
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 ▲]

Detailed reference viewed: 27 (7 ULg)
Full Text
Peer Reviewed
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 ▲]

Detailed reference viewed: 14 (4 ULg)
Full Text
Peer Reviewed
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 ▲]

Detailed reference viewed: 22 (9 ULg)
Full Text
Peer Reviewed
See detailStereoselective synthesis of lanthionine derivatives in aqueous solution and their incorporation into the peptidoglycan of Escherichia coli.
Denoel, Thibaut; Zervosen, Astrid ULg; Gerards, Thomas ULg et al

in Bioorganic & medicinal chemistry (2014), 22(17), 4621-8

The three diastereoisomers-(R,R), (S,S) and meso-of lanthionine were synthesized in aqueous solution with high diastereoselectivity (>99%). The (S) and (R) enantiomers of two differently protected ... [more ▼]

The three diastereoisomers-(R,R), (S,S) and meso-of lanthionine were synthesized in aqueous solution with high diastereoselectivity (>99%). The (S) and (R) enantiomers of two differently protected sulfamidates were opened by nucleophilic attack of (R) or (S)-cysteine. Acidification and controlled heating liberated the free lanthionines. Using the same chemistry, an alpha-benzyl lanthionine was also prepared. The proposed method, which avoids the need of enrichment by recrystallization, opens the way to the labelling of these compounds with (35)S. Furthermore, in vivo bioincorporation into Escherichia coli W7 was studied. No incorporation of alpha-benzyl lanthionine was observed. In contrast, meso-lanthionine can effectively replace meso-diaminopimelic acid in vivo, while in the presence of (R,R)-lanthionine the initial increase of bacterial growth was followed by cell lysis. In the future, meso-[(35)S]lanthionine could be used to study the biosynthesis of peptidoglycan and its turnover in relation to cell growth and division. [less ▲]

Detailed reference viewed: 10 (0 ULg)
Full Text
Peer Reviewed
See detailSynthesis of protected α-alkyl lanthionine derivatives
Denoël, Thibaut; Zervosen, Astrid ULg; Lemaire, Christian ULg et al

in Tetrahedron (2014), 70(30), 4526-4533

Abstract Protected α-alkyl lanthionine derivatives were synthesized in five steps starting from a known phenyloxazoline precursor. This approach involved the synthesis of a family of substituted cyclic ... [more ▼]

Abstract Protected α-alkyl lanthionine derivatives were synthesized in five steps starting from a known phenyloxazoline precursor. This approach involved the synthesis of a family of substituted cyclic sulfamidates and their regioselective opening by nucleophilic attack with a protected cysteine. This efficient multistep strategy affords various α-alkylated lanthionine derivatives in high yields. [less ▲]

Detailed reference viewed: 15 (1 ULg)
Full Text
Peer Reviewed
See detailFully Automated Production of 68Ga-DOTA-NOC with a Trasis miniAIO® Synthesizer
Léonard, Marc ULg; Aerts, Joël ULg; Voccia, Samuel et al

Poster (2013, October 22)

Detailed reference viewed: 60 (14 ULg)
Full Text
Peer Reviewed
See detailSynthesis of [18F]4-(4-fluorophenyl)-1,2,4-triazole-3,5-dione: an agent for specific radiolabelling of tyrosine
Flagothier, Jessica ULg; Warnier, Corentin ULg; Dammicco, Sylvestre ULg et al

in RSC Advances (2013), 3

We developed a new [18F] prosthetic group, the [18F]4-(4-fluorophenyl)-1,2,4-triazole-3,5-dione ([18F]FPTAD), used for its specific ligation with tyrosine-containing peptides or protein in order to ... [more ▼]

We developed a new [18F] prosthetic group, the [18F]4-(4-fluorophenyl)-1,2,4-triazole-3,5-dione ([18F]FPTAD), used for its specific ligation with tyrosine-containing peptides or protein in order to develop a new and versatile radiolabelling technique that could provide a useful tool for new developments in PET imaging. [less ▲]

Detailed reference viewed: 42 (12 ULg)
Full Text
Peer Reviewed
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 ▲]

Detailed reference viewed: 85 (30 ULg)
Full Text
Peer Reviewed
See detailProduction at the Curie Level of No-Carrier-Added 6-18F-Fluoro-L-Dopa
Libert, Lionel ULg; Franci, Xavier; Plenevaux, Alain ULg et al

in Journal of Nuclear Medicine : Official Publication, Society of Nuclear Medicine (2013), 54(7), 1154-1161

6-18F-fluoro-L-dopa (18F-FDOPA) has proven to be a useful radiopharmaceutical for the evaluation of presynaptic dopaminergic function using PET. In comparison to electrophilic synthesis, the no-carrier ... [more ▼]

6-18F-fluoro-L-dopa (18F-FDOPA) has proven to be a useful radiopharmaceutical for the evaluation of presynaptic dopaminergic function using PET. In comparison to electrophilic synthesis, the no-carrier-added (NCA) nucleophilic method has several advantages. These include much higher available activity and specific activity. Recently, we have described an NCA enantioselective synthesis using a chiral phase-transfer catalyst. However, some chemicals were difficult to implement into a commercially available synthesizer, restricting access to this radiopharmaceutical to only a few PET centers. Methods: In this paper, 2 important chemical improvements are proposed to simplify production of 18F-FDOPA, resulting in straightforward automation of the synthesis in a commercially available module. Results: First, a fast, simple, and reliable synthesis of 2-18F-fluoro-4,5-dimethoxybenzyl iodide on a solid phase support was developed. Second, a phase-transfer catalyst alkylation of a glycine derivative at room temperature was used to enable enantioselective carbon–carbon bond formation. After hydrolysis and high-performance liquid chromatography purification, a high enantiomeric excess of 18F-FDOPA (~97%) was obtained using a chiral catalyst available from a biphenyl 3 substrate. The total synthesis time was 63 min, and the decay-corrected radiochemical yield was 36% +/- 3% (n = 8). Conclusion: By exploiting the advantages of this NCA approach, using a starting activity of 185 GBq of NCA 18F-fluoride, high activities of 18F-FDOPA (> 45 GBq) with high specific activity (>753 GBq/mmol) are now available at the end of synthesis for use in clinical investigations. [less ▲]

Detailed reference viewed: 38 (11 ULg)
Full Text
Peer Reviewed
See detailSynthesis of [18F]4-(4-fluorophenyl)-1,2,4-triazole-3,5-dione: an agent for specific radiolabelling of tyrosine.
Flagothier, Jessica ULg; Warnier, Corentin ULg; Lemaire, Christian ULg et al

in Flagothier, Jessica (Ed.) Journal of Labelled Compounds and Radiopharmaceuticals (2013, May 14)

Objectives: Metal-free and mild tyrosine modification reactions are an attractive alternative to the commonly used lysine and cysteine modification protocols for peptide and proteins labelling. Recently ... [more ▼]

Objectives: Metal-free and mild tyrosine modification reactions are an attractive alternative to the commonly used lysine and cysteine modification protocols for peptide and proteins labelling. Recently, Ban and co-workers have reported a tyrosine bioconjugation through ene-type reactions. Cyclic diazodicarboxamides, which are electrophilic compounds, react selectively in o-position on the phenol side chain of tyrosine in mild aqueous conditions and the 1,2,4-triazolidine-3,5-dione linkage is hydrolytically and thermally stable. We herein present the synthesis of [18F]4-(4-fluorophenyl)-1,2,4-triazole-3,5-dione and the coupling with N-acyl tyrosine methylamide. Methods: The N,N,N-trimethyl-4-nitrobenzeneammonium trifluoromethanesulfonate 1 was prepared following a procedure previously reported [2]. The [18F]prosthetic group 6, [18F]4-(4-fluorophenyl)-1,2,4-triazole-3,5-dione, was synthesized in five steps. Results: The synthesis of the [18F]prosthetic group has been realized with a decay-corrected radiochemical yield of 20% in 90 minutes. The radiochemical yield of the coupling with N-acyl tyrosine methylamide is 40% (DC). This presented synthetic pathway should be easily automated: particulary because the purifications between the different steps are exclusively done on SPE cartridges. Conclusions: We successfully developed an efficient bioconjugation method for fluorine-18 labelling of tyrosine without prior modifications of the peptide in very mild conditions. [less ▲]

Detailed reference viewed: 33 (9 ULg)
Full Text
Peer Reviewed
See detailPreclinical radiation dosimetry for the novel SV2A radiotracer [18F]UCB-H
Bretin, Florian ULg; Warnock, Geoffrey; Bahri, Mohamed Ali ULg et al

in European Journal of Nuclear Medicine and Molecular Imaging Research (2013), 3(1), 35

Background: [18F]UCB-H was developed as a novel radiotracer with a high affinity for synaptic vesicle protein 2A, the binding site for the antiepileptic levetiracetam. The objectives of this study were to ... [more ▼]

Background: [18F]UCB-H was developed as a novel radiotracer with a high affinity for synaptic vesicle protein 2A, the binding site for the antiepileptic levetiracetam. The objectives of this study were to evaluate the radiation dosimetry of [18F]UCB-H in a preclinical trial and to determine the maximum injectable dose according to guidelines for human biomedical research. The radiation dosimetry was derived by organ harvesting and dynamic micro positron emission tomography (PET) imaging in mice, and the results of both methods were compared. Methods: Twenty-four male C57BL-6 mice were injected with 6.96 ± 0.81 MBq of [18F]UCB-H, and the biodistribution was determined by organ harvesting at 2, 5, 10, 30, 60, and 120 min (n = 4 for each time point). Dynamic microPET imaging was performed on five male C57BL-6 mice after the injection of 9.19 ± 3.40 MBq of [18F]UCB-H. A theoretical dynamic bladder model was applied to simulate urinary excretion. Human radiation dose estimates were derived from animal data using the International Commission on Radiological Protection 103 tissue weighting factors. Results: Based on organ harvesting, the urinary bladder wall, liver and brain received the highest radiation dose with a resulting effective dose of 1.88E-02 mSv/MBq. Based on dynamic imaging an effective dose of 1.86E-02 mSv/MBq was calculated, with the urinary bladder wall and liver (brain was not in the imaging field of view) receiving the highest radiation. Conclusions: This first preclinical dosimetry study of [18F]UCB-H showed that the tracer meets the standard criteria for radiation exposure in clinical studies. The dose-limiting organ based on US Food and Drug Administration (FDA) and European guidelines was the urinary bladder wall for FDA and the effective dose for Europe with a maximum injectable single dose of approximately 325 MBq was calculated. Although microPET imaging showed significant deviations from organ harvesting, the Pearson’s correlation coefficient between radiation dosimetry derived by either method was 0.9666. [less ▲]

Detailed reference viewed: 49 (16 ULg)
Full Text
Peer Reviewed
See detailQuality controls of no-carrier-added aromatic amino acids such as FDOPA and FTYR produced at curie level
Libert, Lionel ULg; Lemaire, Christian ULg; Giacomelli, Fabrice ULg et al

Poster (2013, May)

Aromatic fluoro amino acids such as 2-[18F]fluoro-L-tyrosine (FTYR) and 6-[18F]fluoro-L-DOPA (FDOPA) are useful radiopharmaceuticals for oncologic studies and evaluation of the presynaptic dopaminergic ... [more ▼]

Aromatic fluoro amino acids such as 2-[18F]fluoro-L-tyrosine (FTYR) and 6-[18F]fluoro-L-DOPA (FDOPA) are useful radiopharmaceuticals for oncologic studies and evaluation of the presynaptic dopaminergic function using positron emission tomography. Recently, a no-carrier-added (nca) enantioselective synthesis of these compounds, based on an multistep PTC approach was automated in a FASTlabTM module from GE . From 185 GBq of [18F]fluoride and after 1 hour of synthesis, more than 37 GBq of FTYR or FDOPA are available . This automated production yields enough doses for many PET studies. A monograph for FDOPA prepared by electrophilic substitution exists , but it is not adapted to the nca nucleophilic synthesis of FDOPA and FTYR, as in this case specific activity, by products and possible impurities are different. A complete quality control (QC) has then be developed in accordance with the guidelines of the European Pharmacopeia (Eur. Ph.). [less ▲]

Detailed reference viewed: 128 (11 ULg)
See detailRadiosynthesis and first small animal microPET imaging of [18F]UCB-H, a new fluorine-18 labelled tracer targeting synaptic vesicle protein 2A (SV2A)
Aerts, Joël ULg; Otabashi, Muhamed; Giacomelli, Fabrice ULg et al

Conference (2013)

Aim. We report the radiosynthesis and first rat microPET imaging of a new fluorine-18 tracer targeting the synaptic vesicle protein 2A, SV2A, identified as the binding site of the antiepileptic drug ... [more ▼]

Aim. We report the radiosynthesis and first rat microPET imaging of a new fluorine-18 tracer targeting the synaptic vesicle protein 2A, SV2A, identified as the binding site of the antiepileptic drug levetiracetam. Materials and Method. Two different nucleophilic radiosynthesis pathways were tested to obtain [18F]UCB-H, a no-carrier-added tracer in the 2-[18F]fluoropyridine family. The methods were automated on FastLab™ synthesizers. PET studies in rodents were carried out using male SD rats, imaged under isoflurane anaesthesia in a Siemens Concorde Focus 120 microPET scanner. Arterial input function was measured using an arteriovenous shunt method and beta microprobe system. All animal protocols were reviewed and accepted by animal ethical committees. Results and conclusion. A radiosynthesis yield of 30% was obtained (uncorrected for decay, 150 minutes of synthesis). Analytical methods were developed and validated to demonstrate that the quality of the tracer solution was compatible with in vivo injection. After intravenous injection, the tracer rapidly entered the brain, followed by rapid washout. PET imaging revealed high uptake of the tracer in the brain and spinal cord, matching the expected SV2A homogeneous distribution. Results indicate that [18F]UCB-H is suitable to quantify SV2A proteins in vivo and to estimate target occupancy of drugs targeting SV2A. Acknowledgments. The authors thank UCB Pharma SA Belgium for collaboration and the Walloon Region Belgium and the FRNS Belgium for financial support. [less ▲]

Detailed reference viewed: 33 (7 ULg)
Full Text
Peer Reviewed
See detailMulticlass classification of FDG PET scans for the distinction between Parkinson's disease and atypical parkinsonian syndromes
Garraux, Gaëtan ULg; Phillips, Christophe ULg; Schrouff, Jessica ULg et al

in NeuroImage: Clinical (2013), 2

Most available pattern recognition methods in neuroimaging address binary classification problems. Here, we used relevance vector machine (RVM) in combination with booststrap resampling (‘bagging’) for ... [more ▼]

Most available pattern recognition methods in neuroimaging address binary classification problems. Here, we used relevance vector machine (RVM) in combination with booststrap resampling (‘bagging’) for non-hierarchical multiclass classification. The method was tested on 120 cerebral 18fluorodeoxyglucose (FDG) positron emission tomography (PET) scans performed in patients who exhibited parkinsonian clinical features for 3.5 years on average but that were outside the prevailing perception for Parkinson's disease (PD). A radiological diagnosis of PD was suggested for 30 patients at the time of PET imaging. However, at follow-up several years after PET imaging, 42 of them finally received a clinical diagnosis of PD. The remaining 78 APS patients were diagnosed with multiple system atrophy (MSA, N = 31), progressive supranuclear palsy (PSP, N = 26) and corticobasal syndrome (CBS, N = 21), respectively. With respect to this standard of truth, classification sensitivity, specificity, positive and negative predictive values for PD were 93% 83% 75% and 96%, respectively using binary RVM (PD vs. APS) and 90%, 87%, 79% and 94%, respectively, using multiclass RVM (PD vs. MSA vs. PSP vs. CBS). Multiclass RVM achieved 45%, 55% and 62% classification accuracy for, MSA, PSP and CBS, respectively. Finally, a majority confidence ratio was computed for each scan on the basis of class pairs that were the most frequently assigned by RVM. Altogether, the results suggest that automatic multiclass RVM classification of FDG PET scans achieves adequate performance for the early differentiation between PD and APS on the basis of cerebral FDG uptake patterns when the clinical diagnosis is felt uncertain. This approach cannot be recommended yet as an aid for distinction between the three APS classes under consideration. [less ▲]

Detailed reference viewed: 38 (11 ULg)
Full Text
Peer Reviewed
See detailEpisodic autobiographical memory in amnestic Mild Cognitive Impairment: What are the neural correlates?
Bastin, Christine ULg; Feyers, Dorothée ULg; Jedidi, Haroun ULg et al

in Human Brain Mapping (2013), 34

Autobiographical memory in amnestic Mild Cognitive Impairment (aMCI) is characterized by impaired retrieval of episodic memories, but relatively preserved personal semantic knowledge. This study aimed to ... [more ▼]

Autobiographical memory in amnestic Mild Cognitive Impairment (aMCI) is characterized by impaired retrieval of episodic memories, but relatively preserved personal semantic knowledge. This study aimed to identify (via FDG-PET) the neural substrates of impaired episodic specificity of autobiographical memories in 35 aMCI patients compared with 24 healthy elderly controls. Significant correlations between regional cerebral activity and the proportion of episodic details in autobiographical memories from two life periods were found in specific regions of an autobiographical brain network. In aMCI patients, more than in controls, specifically episodic memories from early adulthood were associated with metabolic activity in the cuneus and in parietal regions. We hypothesized that variable retrieval of episodic autobiographical memories in our aMCI patients would be related to their variable capacity to reactivate specific sensory-perceptual and contextual details of early adulthood events linked to reduced (occipito-parietal) visual imagery and less efficient (parietal) attentional processes. For recent memories (last year), a correlation emerged between the proportion of episodic details and activity in lateral temporal regions and the temporo-parietal junction. Accordingly, variable episodic memory for recent events may be related to the efficiency of controlled search through general events likely to provide cues for the retrieval of episodic details and to the ability to establish a self perspective favouring recollection. [less ▲]

Detailed reference viewed: 92 (34 ULg)
Full Text
Peer Reviewed
See detailDosimetry for 6-[18F]Fluoro-L-DOPA in Humans Based on Biodistribution in Mice
Bretin, Florian ULg; Warnock, Geoffrey ULg; Bahri, Mohamed Ali ULg et al

Poster (2012, October)

Aim. The objective of this work was to estimate human dosimetry for 6-[18F]Fluoro-L-DOPA (F-DOPA) from biodistribution in mice, obtained from organ harvesting at different time points and from a hybrid ... [more ▼]

Aim. The objective of this work was to estimate human dosimetry for 6-[18F]Fluoro-L-DOPA (F-DOPA) from biodistribution in mice, obtained from organ harvesting at different time points and from a hybrid method combining dynamic PET followed by organ harvesting. Materials and methods. The tissue distribution of F-DOPA over time was determined in isoflurane-anaesthetized mice. Radioassay was performed on harvested organs at 2, 5, 10, 30, 60 and 120 minutes post administration (n = 5 at each time point). Dynamic PET images were acquired in list-mode with a Siemens FOCUS 120 microPET for 120 minutes after injection and followed by radioassay of harvested organs (n = 4). List-mode data were histogrammed in 6*5s, 6*10s, 3*20s, 5*30s, 5*60s, 8*150s, 6*300s, 6*600s 3D sinograms. Final images were obtained using filtered backprojection with correction for all physical effects except for scatter. Attenuation correction resulted from a pre-injection transmission scan with a cobalt-57 point source. Organs were manually delineated. The organ time-activity-curves (TACs) from both methods were extrapolated from a simulated 35 g standard mouse to a 70 kg standard male human using a technique based on organ to bodyweight ratios. A bladder voiding scenario was used to simulate excretion every 2 h. The absorbed doses in major human organs were calculated using the extrapolated TACs with the commercially available software OLINDA/EXM (Version 1.1). Results. The extrapolated organ activity curves obtained using the harvesting and imaging methods showed a high correlation (r = 0.94 ± 0.05, p < 0.001). However, TACs from PET alone under- or overestimated the activity in individual organs in contrast to TACs obtained using the cross-calibration of the PET data with the activity in post-scan dissected organs. Those organs in the excretion pathways, comprising bladder wall, kidneys and liver, received the highest organ doses. The total body absorbed dose was 0.0118 mGy/MBq for both the imaging based and harvesting based methods. The effective dose was 0.0193 mSv/MBq for the hybrid imaging-harvesting technique and 0.0189 mSv/MBq for the pure harvesting technique. Conclusion. The doses obtained agreed well with the few results available in the literature. The hybrid technique combining dynamic PET scanning followed by organ harvesting appeared to be a good alternative to the gold standard ex vivo radioassay method. It is much faster and minimizes the effect of some weakness of the pure imaging technique, such as partial volume effect. [less ▲]

Detailed reference viewed: 41 (8 ULg)