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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) (in press)

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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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)

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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 ▲]

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See detailCustomizing an adaptive case management software in a GMP production lab as a quality management system for clinical trial PET radiopharmaceuticals development and production
Aerts, Joël ULg; Renard; Léonard, Marc ULg et al

Poster (2013)

The Cyclotron Research Centre (CRC) of the University of Liège develops and produces innovative radiopharmaceuticals for research and clinical diagnostic applications in humans. We report our recent ... [more ▼]

The Cyclotron Research Centre (CRC) of the University of Liège develops and produces innovative radiopharmaceuticals for research and clinical diagnostic applications in humans. We report our recent experience in the implementation of an adaptive case management software as a tool of tractability and quality management in our GMP1 facility. [less ▲]

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See detailEvaluation of a new [18F] labeled tracer targeting synaptic vesicle protein 2C by ex vivo autoradiography and in vivo PET study in rat brain.
Warnock, Geoffrey; Aerts, Joël ULg; Mestdagh, Nathalie et al

Poster (2013)

Introduction The synaptic vesicle protein 2 (SV2) family is a group of integral membrane glycoproteins homologous to the major facilitator superfamily and could be involved in several neuronal diseasesa ... [more ▼]

Introduction The synaptic vesicle protein 2 (SV2) family is a group of integral membrane glycoproteins homologous to the major facilitator superfamily and could be involved in several neuronal diseasesa. The binding of the novel, no-carrier-added, [18F] labeled compound [18F]UCB-F to the SV2C isoform was evaluated in rat brain. Methods Radiochemistry No-carrier added [18F]UCB-F was obtained following the method shown in Fig. 1. The identity and purity of the tracer were evaluated by radioUPLC and chiral radioHPLC. Autoradiography Sprague Dawley rat brain sections were incubated at RT with buffered [18F]UCB-F solutions and exposed on film. Matching sections were stained with cresyl violet for structural identification. PET studies PET studies (Siemens Concorde Focus 120 µPET) were performed under isoflurane anesthesia. The tracer was injected as a bolus via the tail vein. After a 10-min transmission scan to correct for attenuation, dynamic emission data was recorded for a total of 60 min. The impact of P-glycoprotein (P-gp) activity on tracer uptake in the brain was evaluated using cyclosporine (50 mg/kg SC). Metabolite analysis During PET studies, arterial blood samples were taken for the measurement of tracer metabolites. Plasma was separated by centrifugation and proteins were acid-precipitated. Metabolites were detected using HPLC and confirmed by gamma counting. Results The tracer was obtained with a decay corrected yield of ±10%. Specific activity ranged from 10 GBq/µmol to 40 GBq/µmol. Ex vivo autoradiography showed that the binding of [18F]UCB-F to SV2C closely matched the expected distribution b (Fig.2). In vivo PET studies revealed that [18F]UCB-F briefly entered the brain, but exhibited extremely rapid washout. A large accumulation in the liver and intestines was observed. Metabolite analysis in the plasma revealed high protein binding and rapid metabolism. Inhibition of P-gp transport with cyclosporin had no clear effect on the rapid washout from the brain. Conclusions Despite a close match between [18F]UCB-F SV2C binding and the expected brain distribution, the pharmacokinetics in rat brain appear unfavorable for the use of this tracer to quantify SV2C in vivo. Acknowledgement / References a Lynch & al (2004) Proc. Natl. Acad. Sci. USA 101:9861 b Janz & Sudhof (1999) Neuroscience 94:1279 c The authors thank the Walloon Region and the FRNS Belgium for financial support. [less ▲]

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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 ▲]

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See detailCHARACTERIZATION OF A NOVEL RADIOTRACER TARGETING SYNAPTIC VESICLE PROTEIN 2A (SV2A)
Warnock, Geoffrey ULg; Aerts, Joël ULg; Bahri, Mohamed Ali ULg et al

Poster (2012, September)

Synaptic vesicle protein 2A (SV2A) has been identified as the binding site of the antiepileptic levetiracetam (Keppra) [1]. SV2 proteins are critical for proper nervous system function and have been ... [more ▼]

Synaptic vesicle protein 2A (SV2A) has been identified as the binding site of the antiepileptic levetiracetam (Keppra) [1]. SV2 proteins are critical for proper nervous system function and have been demonstrated to be involved in vesicle trafficking. Their implication in epilepsy makes them an interesting therapeutic target, and the widespread distribution of SV2A in particular may provide an opportunity to develop a PET-based measure of neuronal function in brain diseases. [18F]UCB-H is a fluorine-18 radiolabelled PET imaging agent with a nanomolar affinity for the human SV2A protein. Preclinical 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. [18F]UCB-H was injected IV (3.8 ± 0.54 mCi bolus, specific activity 8.5 ± 0.86 Ci/Emol immediately after synthesis) and dynamic PET data acquired in list mode for 90 min. Images were reconstructed using filtered back projection with correction for all physical effects except scatter. These scans revealed high uptake of [18F]UCB-H in brain and spinal cord, matching the expected homogeneous distribution of SV2A in the rodent brain [2]. Notably, the kinetics of [18F]UCB-H uptake in the brain were fast, peaking at up to 30 % ID/cm3 before a rapid decline. Metabolism of [18F]UCB-H in vivo followed a typical pattern of rapid initial metabolism followed by a reducing rate of metabolism over time, with less than 20% of the activity in plasma attributable to the parent compound after 30 minutes, and was highly reproducible between subjects. One major metabolite was identified. The uptake of [18F]UCB-H in the brain over time was well fitted by a classical 1-tissue compartment model. Mean parameter estimates (mean ± SD, n=7, whole brain VOI) were K1: 3.58 ± 0.65 ml/cm3/min, k2: 0.21 ± 0.03 min-1, Vt: 17.21 ± 2.52 ml/cm3. Uptake of [18F]UCB-H was blocked by pretreatment with brivaracetam (21 mg/kg IV, 10 min prior to [18F]UCB-H), a recently described high affinity SV2A ligand with a 20-fold higher affinity for SV2A than levetiracetam [3]. In contrast, pretreatment with ucb-100230-1, a diastereoisomer of brivaracetam with 3200-fold lower affinity for SV2A [3], had no clear effect of the brain uptake of [18F]UCB-H. Our results indicate that [18F]UCB-H is a suitable radiotracer for the quantification of SV2A proteins in vivo and for estimating target occupancy of drugs targeting SV2A. 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 have been completed and first in human studies are planned. References [1] Lynch, B.A. et al. (2004) PNAS 101(26):9861-6. [2] Janz, R. & Sudhof, T.C. (1999) Neuroscience 94(4):1279-1290.[3] Gillard, M. et al. (2011) Eur J Pharmacol 664:36-44. [less ▲]

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See detailUse of a beta microprobe system to measure arterial input function in PET via an arteriovenous shunt in rats
Warnock, Geoffrey ULg; Bahri, Mohamed Ali ULg; Goblet, David ULg et al

in European Journal of Nuclear Medicine and Molecular Imaging Research (2011), 1

Kinetic modeling of physiological function using imaging techniques requires the accurate measurement of the time-activity curve of the tracer in plasma, known as the arterial input function (IF). The ... [more ▼]

Kinetic modeling of physiological function using imaging techniques requires the accurate measurement of the time-activity curve of the tracer in plasma, known as the arterial input function (IF). The measurement of IF can be achieved through manual blood sampling, the use of small counting systems such as beta microprobes, or by derivation from PET images. Previous studies using beta microprobe systems to continuously measure IF have suffered from high background counts. In the present study, a light-insensitive beta microprobe with a temporal resolution of up to 1 s was used in combination with a pump-driven femoral arteriovenous shunt to measure IF in rats. The shunt apparatus was designed such that the placement of the beta microprobe was highly reproducible. The probe-derived IF was compared to that obtained from manual sampling at 5-s intervals and IF derived from a left ventricle VOI in a dynamic PET image of the heart. Probe-derived IFs were very well matched to that obtained by "gold standard" manual blood sampling, but with an increased temporal resolution of up to 1 s. The area under the curve (AUC) ratio between probe- and manually derived IFs was 1.07 ± 0.05 with a coefficient of variation of 0.04. However, image-derived IFs were significantly underestimated compared to the manually sampled IFs, with an AUC ratio of 0.76 ± 0.24 with a coefficient of variation of 0.32. IF derived from the beta microprobe accurately represented the IF as measured by blood sampling, was reproducible, and was more accurate than an image-derived technique. The use of the shunt removed problems of tissue-background activity, and the use of a light-tight probe with minimal gamma sensitivity refined the system. The probe/shunt apparatus can be used in both microprobe and PET studies. [less ▲]

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See detail18F-fluoride PET/CT for assessing bone involvement in prostate and breast cancers
Withofs, Nadia ULg; Grayet, Benjamin ULg; Tancredi, Tino ULg et al

in Nuclear Medicine Communications (2011), 32(3), 168-176

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See detailSynthesis and hydrolytic stability of novel 3-[18F]fluoroethoxybis(1-methylethyl)silyl]propanaminebased prosthetic groups
collet, Charlotte; Lamandé-Langle, Sandrine; Balentova, Eva et al

Poster (2011)

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See detailNeural correlates of controlled memory processes in questionable Alzheimer’s disease
Bastin, Christine ULg; Kerrouche, Nacer; LEKEU, Françoise ULg et al

in Ashford, J. Wesson; Rosen, Allyson; Adamson, Maheen (Eds.) et al Advances in Alzheimer's Disease. Volume 2: Handbook of imaging the Alzheimer brain (2011)

Alzheimer’s disease (AD) is characterized by a progressive loss of controlled cognitive processes (processes requiring mental effort and attentional resources), and functional neuroimaging at early stages ... [more ▼]

Alzheimer’s disease (AD) is characterized by a progressive loss of controlled cognitive processes (processes requiring mental effort and attentional resources), and functional neuroimaging at early stages of AD provides an opportunity to tease out the neural correlates of controlled processes. Controlled and automatic memory performance was assessed with the Process Dissociation Procedure in 50 patients diagnosed with questionable Alzheimer’s disease (QAD). The patients’ brain glucose metabolism was measured using FDG-PET. After a follow-up period of 36 months, 27 patients had converted to AD, while 23 remained stable. Both groups showed a similar decrease in controlled memory processes but preserved automatic processes at entry into the study, suggesting that impairment of controlled memory would not be specific for AD. Patients who subsequently converted to Alzheimer type dementia showed significantly decreased brain metabolism at baseline compared to stable QAD in associative cortices known to be involved in AD (the left precuneus, the right inferior parietal lobule and bilateral middle temporal cortex).Voxel-based cognitive and metabolic correlations showed that a decrease in controlled memory processes was preferentially correlated with lower activity in the dorsomedial prefrontal and posterior cingulate cortices in very early AD patients. The dorsomedial prefrontal cortex would play a role in controlled memory processes as they relate to reflective and monitoring processes, while the posterior cingulate cortex is involved in the controlled access to previously encoded episodes. In stable QAD patients, reduced controlled performance in verbal memory correlated with impaired activity in the left anterior hippocampal structure, which would alter the reactivation of associations created at encoding. [less ▲]

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See detailSynthesis and hydrolytic stability of novel 3-[18F]fluoroethoxybis(1-methylethyl)silyl]propanamine-based prosthetic groups
Balentova, Eva; Collet, Charlotte; Lamande-Langle, Sandrine et al

in Journal of Fluorine Chemistry (2011), 132(4), 250-257

Two new silicon-based prosthetic groups, derived from 3-[ethoxybis(1-methylethyl)silyl]propanamine, have been prepd. in good yields. These silicon groups bearing an acid or an azide group were coupled to ... [more ▼]

Two new silicon-based prosthetic groups, derived from 3-[ethoxybis(1-methylethyl)silyl]propanamine, have been prepd. in good yields. These silicon groups bearing an acid or an azide group were coupled to a model tripeptide (Leu-Gly- Gly) either through a classical amide bond formation or through "click chem." via the Huisgen cycloaddn. The radiolabeling with fluorine-18 by substitution of the ethoxy group at silicon has been carried out with success in 51-54% decay cor. radiochem. yields. Radiolabeled peptides were easily prepd. by direct 18F-fluorination of the silicon-bearing tripeptide or by coupling the peptide with a radiolabeled silicon-based prosthetic group. Their stabilities in physiol. medium were studied and proved poor. [less ▲]

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See detailFully Automated Preparation and Conjugation of N-Succinimidyl 4-[(18)F]Fluorobenzoate ([ (18)F]SFB) with RGD Peptide Using a GE FASTlab Synthesizer.
Thonon, David ULg; Goblet, D.; Goukens, Eve ULg et al

in Molecular imaging and biology : MIB : the official publication of the Academy of Molecular Imaging (2011)

PURPOSE: The aim of this work was to automate the radiosynthesis of [(18)F]SFB, a widely used reagent for the labeling of biomolecules with (18)F on a new generation commercial synthesis module (FASTLab ... [more ▼]

PURPOSE: The aim of this work was to automate the radiosynthesis of [(18)F]SFB, a widely used reagent for the labeling of biomolecules with (18)F on a new generation commercial synthesis module (FASTLab, GE Healthcare). PROCEDURES: Two synthesis approaches were implemented on this module: the classical "two-pot radiosynthesis" and the more recently described "one-pot" method. RESULTS: The "two-pot" approach affords [(18)F]SFB with a 42% decay-corrected yield in 57 min (n = 24) with a chemical purity sufficient to avoid an intermediate HPLC purification. The recently established "one-pot" method, afforded a product with a lower chemical purity, in the conditions used in this report. The lower d.c. yield obtained (32% (n = 15)) was related to the low (18)F labeling yields obtained in MeCN compared with DMSO. The subsequent conjugation step with a RGD (PRGD2) peptide was also successfully automated. CONCLUSIONS: The formulated [(18)F]FPRGD2 was obtained without any operator manipulation with a d.c. yield of 13% +/- 3% (n = 13) in 130 min, a radiochemical purity >98% and a specific activity of 140 +/- 40 TBq/mmol. [less ▲]

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See detailControlled Memory Processes in Questionable Alzheimer's Disease: A View from Neuroimaging Research
Bastin, Christine ULg; Kerrouche N; Lekeu, Françoise ULg et al

in Journal of Alzheimer's Disease [=JAD] (2010), 20(2), 547-560

Alzheimer's disease (AD) is characterized by a progressive loss of controlled cognitive processes, and neuroimaging studies at early stages of AD provide an opportunity to tease out the neural correlates ... [more ▼]

Alzheimer's disease (AD) is characterized by a progressive loss of controlled cognitive processes, and neuroimaging studies at early stages of AD provide an opportunity to tease out the neural correlates of controlled processes. Accordingly, controlled and automatic memory performance was assessed with the Process Dissociation Procedure in 50 patients diagnosed with questionable Alzheimer's disease (QAD). The patients' brain glucose metabolism was measured using FDG-PET. After a follow-up period of 36 months, 27 patients had converted to AD, while 23 remained stable. Both groups showed a similar decrease in controlled memory processes but preserved automatic processes at entry into the study. Voxel-based cognitive and metabolic correlations showed that a decrease in controlled memory processes was preferentially correlated with lower activity in the dorsomedial prefrontal and posterior cingulate cortices in very early AD patients. In stable QAD patients, reduced controlled performance in verbal memory correlated with impaired activity in the left anterior hippocampal structure. The results demonstrated the central role of a medial frontal-posterior cingulate network for controlled processing of episodic memory in the early stages of AD. [less ▲]

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See detailFast Production of Highly Reactive No-Carrier-Added [18F]Fluoride for the Labeling of Radiopharmaceuticals
Lemaire, Christian ULg; Aerts, Joël ULg; Voccia, Samuel et al

in Angewandte Chemie (International ed. in English) (2010), 49

The 18F labeling of radiopharmaceuticals requires nearly anhydrous solutions of [18F]fluoride. Aqueous K2CO3 is generally used to elute [18F]fluoride from an anion-exchange resin. Replacing aqueous K2CO3 ... [more ▼]

The 18F labeling of radiopharmaceuticals requires nearly anhydrous solutions of [18F]fluoride. Aqueous K2CO3 is generally used to elute [18F]fluoride from an anion-exchange resin. Replacing aqueous K2CO3 with strong organic bases, such as the phosphazene base P2Et enabled the recovery of highly reactive [18F]fluoride and avoided the azeotropic evaporation of water, which is very difficult on a microchip device. [less ▲]

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See detailFast production of highly concentrated reactive [18F] fluoride for aliphatic and aromatic nucleophilic radiolabelling
Aerts, Joël ULg; Voccia, Samuel; Lemaire, Christian ULg et al

in Tetrahedron Letters (2010), 51

The use of a polymeric solid support loaded with a long alkyl chain quaternary ammonium allows the rapid and efficient recovery of cyclotron produced [18F]F- from [18O]water to a low water content organic ... [more ▼]

The use of a polymeric solid support loaded with a long alkyl chain quaternary ammonium allows the rapid and efficient recovery of cyclotron produced [18F]F- from [18O]water to a low water content organic solution compatible with fast nucleophilic labelling of most precursors for PET radiopharmaceuticals in high yield. [less ▲]

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