THE EFFECT OF BETA MICROPROBE IMPLANTATION ON THE BLOOD BRAIN BARRIER

Poster (2010, September)

Controlled Memory Processes in Questionable Alzheimer's Disease: A View from Neuroimaging Research

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 ▲]

Automated radiosynthesis of [18F]MPPF derivatives for imaging 5-HT1A receptors

Poster (2010, May 30)

TOPIC: Molecular Neuroimaging: from Bench to Bedside Automated radiosynthesis of [18F]MPPF derivatives for imaging 5-HT1A receptors Introduction: Dysfunction of the cerebral serotoninergic system is ... [more ▼]

TOPIC: Molecular Neuroimaging: from Bench to Bedside Automated radiosynthesis of [18F]MPPF derivatives for imaging 5-HT1A receptors Introduction: Dysfunction of the cerebral serotoninergic system is implicated in numerous neurodegenerative disorders such as Alzheimer disease’s, dementia, depression, anxiety, schizophrenia, and Parkinson disease’s. The 5-HT1A serotonin receptors are involved in several physiological functions including sleep, mood, neurogenesis and learning [1]. Consequently, there have been huge efforts in finding ligands for this receptor. [11C]WAY-100635 is a high affinity radioligand used for quantifying serotonin 5-HT1A receptors with positron emission tomography. An 18F-labeled radioligand is advantageous because of higher specific activity and physical/nuclear properties (t1/2= 109 min, 97% of positron decay and positron energy of 635 keV maximum). [18F]MPPF, a selective 5-HT1A antagonist derived from WAY-100635, is currently one of the most successful PET ligand used for 5-HT1A receptor imaging [2]. However the affinity is lower then WAY-100635 and the amount of [18F]MPPF reaching the brain is relatively low since MPPF is a substrate for p-glycoprotein [3]. Methods: In order to improve the brain uptake of the radiotracer, a desmethylated analog has been developed in our lab and preliminary in vitro studies show positive results [4]. Nevertheless, the radiosynthesis take place in two steps as a protecting group removal is needed. A one step procedure with a MPPF derivative could be of very great interest. We have synthesized many MPPF derivatives in our lab (modification on the phenylpiperazine moiety) and developed an automated radiosynthesis procedure for the production of these radiotracers. [18F]MPPF was chosen as the model compound. We used a GE Healthcare FASTlabTM module and made modifications to the [18F]FDG synthesis sequence and cassette. [18F]MPPF was synthesized by coupling of [18F]FBA with the corresponding amine. After coupling, the crude solution was diluted with water and passed through a tC18 cartridge for prepurification. After elution, the [18F]MPPF was purified by semi-preparative HPLC. Results: Total synthesis time, including purification was approximately 100 min. [18F]FBA and [18F]MPPF were obtained at a corrected yield of 55% (n=20) and 25% (n=5) respectively. The radiochemical purity, checked by radio-TLC and UPLC, was >95%. Conclusions: We have developed an automated method for [18F]MPPF and derivatives production using a commercial synthesizer (FASTlabTM from GE Healthcare) and a conventional HPLC system resulting in good yields and high (radio)chemical purity. By simply switching the vial containing the modified amine, an 18F-labeled MPPF derivative could be obtained. Radiosynthesis is still under optimization and the radiotracers synthesized need to be tested as suitable 5-HT1A radioligands. Acknowledgement: This work was supported by the Fondation Rahier. References: [1] Filip M., Bader M. et Al, Pharmacol Rep. 2009 Sep-Oct; 61(5):761-77 [2] Aznavour N, Zimmer L. Et Al, Neuropharmacology. 2007 Mar; 52(3):695-707 [3] Laćan G., Plenevaux A. et Al, Eur J Nucl Med Mol Imaging. 2008 Dec;35(12):2256-66 [4] Defraiteur C., Plenevaux A. et Al., Br J Pharmacol. 2007 Nov; 152(6):952-8 [less ▲]

Fast Production of Highly Reactive No-Carrier-Added [18F]Fluoride for the Labeling of Radiopharmaceuticals

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 ▲]

Automatic brain image reading for the differential diagnosis between atypical parkinsonian syndromes & Parkinson's disease

in Movement Disorders : Official Journal of the Movement Disorder Society (2010), 25(7), 379-379

Accurate measurement of arterial input function during FDG PET using a beta microprobe

in Journal of Cerebral Blood Flow & Metabolism (2009, October), 29(S1), 339-339

Comparaison of reference tissue model versus two compartement model with input function for [18F]Fallypride modelling. A combined microPET-Beta microprobe study in rat.

in Journal of Labelled Compounds & Radiopharmaceuticals (2009, July 12), 52(S1), 108

USE OF A BETA MICROPROBE SYSTEM AS AN AFFORDABLE TRANSLATIONAL TOOL COMPARED TO PET – EXAMPLES USING FDG AND 18F-FALLYPRIDE BINDING

in Journal of Labelled Compounds & Radiopharmaceuticals (2009, July), 52(S1), 55

Modified Non-Ionic Solid Supports: a Way to High Activity Fluorine-18 Radiochemistry in Microfluidic Devices

in Journal of Labelled Compounds & Radiopharmaceuticals (2009, July), 52(S1), 12

New Improvements in the Enantioselective Synthesis of 2-[18F]Fluoro-L-Tyrosine and 6-[18F]Fluoro-L-Dopa

in Journal of Labelled Compounds & Radiopharmaceuticals (2009, July), 52(S1), 196