Uppsala, Sweden
Uppsala, Sweden

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Agency: European Commission | Branch: FP7 | Program: CP-FP | Phase: HEALTH.2013.2.2.1-2 | Award Amount: 6.99M | Year: 2013

The key concept behind this proposal is the development of a very high resolution and high efficiency brain dedicated Positron Emission Tomograph (PET) imager that can visualize neurotransmitter pathways and their disruptions in the quest to better diagnose and consequently to better treat schizophrenia. In addition, the plan is for this compact PET imager to be integrated with a Magnetic Resonance Imager Radio Frequency (MRI RF) system to be able to operate as a brain insert in a hybrid imaging setup with practically any MRI scanner. From the technical point of view, we propose to optimize the PET technology for imaging of the human brain with the accuracy typically achieved for small animal brain imaging. To achieve this, we will incorporate the solid state based MRI-compatible PET modules that will be designed to achieve below systemic 1mm spatial resolution in a tomographic reconstruction of the human brain. We aim to achieve the level of PET-MRI compatibility allowing for simultaneous PET and MRI imaging. By combining PET measurements of neurotransmission with fMRI (functional MRI) measurements of Blood Oxygen Level Detection (BOLD) signal changes we will advance to a position where it is possible to learn more about the neurochemical determination of neural activity reflected in BOLD signal changes. The novelty is that both the PET and RF coil systems are integrated into a portable and compact design dedicated to brain examination. This will allow current MR equipment to be easily upgraded into PET/MR systems. To achieve its diagnostic goal, MINDView will be paired with the set of dedicated specific PET imaging agents and endogenous compounds that will be labeled with short-lived positron isotopes. The goal is that dopaminergic, glutamatergic and other pathways will be able to be studied with the new high performance imaging tool. Innovative paradigms such as activation and perturbation and their impact on brain function will be in focus.

Agency: European Commission | Branch: FP7 | Program: CP-IP | Phase: NMP-2010-4.0-1 | Award Amount: 13.81M | Year: 2011

SaveMe project will address current urgent needs for pancreatic cancer diagnosis and treatment by exploiting partners expertise and most recent research achievements for the design and development of novel modular nanosystems platform integrating new functionalized nano-core particles and active agents. The modular platform will enable the design of diverse active nanosystems per diagnostic or therapeutic application as defined by their active agent compositions. For diagnostics, superior tracers will be developed for molecular MR/PET and gamma camera imaging, enabling efficient diagnosis and guided surgery respectively. Novel functionalized nano-core systems will be conjugated with semi-confluent active shell layer. Three types of shell layers will be design: (1) novel iron oxide nanoparticles as advanced MRI contrast agents and/or (2) DOTA complexes for MRI (with Gd3\), or PET (with Ga-68), or gamma camera (with Ga-69); (3) Integrating within one tracer both iron oxide nanoparticles and DOTA-Ga-68 complexes for a sequential or simultaneous MR/PET imaging. For therapeutics, active nanosystems will be developed to deliver (1) therapeutic siRNAs or (2) anti-MP-inhibitory-scFVs. These non-classic anti-tumor drugs will be designed based on an extensive tumor degradome analysis for combining blockage of selective matrix MPs, thus preventing basic invasive and metastasis steps, with siRNA based neutralization of secondary molecular effects induced by the specific protease inhibition. Individualized degradome analysis will be developed for potential profiling of anti-MP and siRNAs based therapy per patient. To facilitate the above diagnostics and therapeutic effects, advanced tumor targeting and penetration active agents will be linked to nano-core functionalized groups, including a biocompatible PEG layer linked to tumor selective MMP substrate molecules and highly safe and potent novel somatostatin analogue peptides targeting SSTR overexpression.

Dahl K.,Karolinska Institutet | Itsenko O.,GEMS PET Systems AB | Itsenko O.,Sahlgrenska University Hospital | Rahman O.,Karolinska Institutet | And 8 more authors.
Journal of Labelled Compounds and Radiopharmaceuticals | Year: 2015

[11C]Carbon monoxide (11CO) is a versatile building block for the synthesis of Positron Emission Tomography (PET) radioligands. However, the difficulty of trapping 11CO in a small solvent volume has limited its utility. We here report an evaluation of a simple, fully automated high-pressure synthesizer prototype for the use in 11C-carbonylation reactions. [11C]Carbon monoxide was easily prepared by online reduction of [11C]carbon dioxide using either Mo(s) or Zn(s) as the reducing agent. The conversion yield of 11CO was >99% when zinc was used as the reducing agent, and the corresponding value for Mo was approximately 71%. When the Zn or Mo column was constantly kept under inert atmosphere, no significant decrease in reducing properties was observed for more than 100 11CO productions. However, in our hands, Mo reductant was much easier to service. A total of nine functional groups were successfully radiolabeled using the 11CO synthesizer prototype. All measured radiochemical yields exceeded 37%, and the 11CO trapping efficiency was generally above 90%, except for the Suzuki coupling where the trapping efficiency was 80%. This high-pressure synthesizer using [11C]carbon monoxide as the labeling precursor is easy to operate allowing for 11C-carbonylation reactions to be performed in a high yield and in a routinely fashion. Copyright © 2015 John Wiley & Sons, Ltd.

Rahman O.,Karolinska Institutet | Rahman O.,Bencar AB
Journal of Labelled Compounds and Radiopharmaceuticals | Year: 2015

[11C]Carbon monoxide is an attractive precursor for labeling carbonyl position in a wide range of organic compounds. The use of [11C]carbon monoxide in transition metal-mediated coupling reactions has been explored by several groups during the last 15 years, and an impressive number of the synthesis of [carbonyl-11C]compounds have been published to date. The application of radical-mediated [11C]carbonylation has also been explored in some extent. However, the main limitations to apply this potential precursor in 11C-labeling chemistry are low concentration, poor solubility in commonly used organic solvents, and low reactivity. A couple of technical solutions such as high-pressure reactor system, microfluidic system, and different approaches to confine [11C]CO to the reaction media at ambient pressure have been developed over the years. Although considerable advances in [11C]carbon monoxide chemistry have been reported in recent years, its application in positron emission tomography tracer development is still an area of work in progress. This review summarizes all contributions to the area of radiolabeling using [11C]carbon monoxide published between 1995 and 2014 and discusses the scope and limitations of this method in clinical positron emission tomography tracer development. © 2015 John Wiley & Sons, Ltd.

Dahl K.,Karolinska Institutet | Schou M.,Astrazeneca | Ulin J.,Bencar AB | Sjoberg C.-O.,Bencar AB | And 3 more authors.
RSC Advances | Year: 2015

A novel gas-liquid segmented microfluidic platform has been developed. The Pd-mediated 11C-carbonylation reaction proceeds smoothly on this platform and good to excellent radiochemical conversions (RCC) were observed. Twelve compounds were successfully radiolabelled using this novel technology, including the well established D2 receptor radioligands [11C]raclopride and [11C]FLB 457. © The Royal Society of Chemistry.

Rahman O.,Karolinska University Hospital | Rahman O.,Bencar AB | Rahman O.,Uppsala University | Takano A.,Karolinska University Hospital | And 8 more authors.
Nuclear Medicine and Biology | Year: 2015

Introduction: The selective dopamine D2 receptor antagonist raclopride is usually labeled with carbon-11 using [11C]methyl iodide or [11C]methyl triflate for use in the quantification of dopamine D2 receptors in human brain. The aim of this work was to label raclopride at the carbonyl position using [11C]carbon monoxide chemistry and to compare ([11C]carbonyl)raclopride with ([11C]methyl)raclopride in non-human primate (NHP) using PET with regard to quantitative outcome measurement, metabolism of the labeled tracers and protein binding. Methods: Palladium-mediated carbonylation using [11C]carbon monoxide, 4,6-dichloro-2-iodo-3-methoxyphenol and (S)-(-)-2-aminomethyl-1-ethylpyrrolidine was applied in the synthesis of ([11C]carbonyl)raclopride. The reaction was performed at atmospheric pressure using xantphos as supporting phosphine ligand and palladium (π-cinnamyl) chloride dimer as the palladium source. ([11C]Methyl)raclopride was prepared by a previously published method. In the PET study, two female cynomolgus monkeys were used under gas anesthesia of sevoflurane. A dynamic PET measurement was performed for 63min with an HRRT PET camera after intravenous injection of ([11C]carbonyl)raclopride and ([11C]methyl)raclopride, respectively, during the same day. The order of injection of the two PET radioligands was changed between the two monkeys. The venous blood sample for measurement of protein binding was taken 3min prior to the PET scan. Binding potential (BPND) of the putamen and caudate was calculated with SRTM using the cerebellum as a reference region. Results: The target compound ([11C]carbonyl)raclopride was obtained with 50±5% decay corrected radiochemical yield and 95% radiochemical purity. The trapping efficiency (TE) of [11C]carbon monoxide was 65±5% and the specific radioactivity of the final product was 34±1GBq/μmol after a 50min of synthesis time. The radiochemical yield of ([11C]methyl)raclopride was in the same range as published previously i. e. 50-60% and specific radioactivity of those two batches which were used in the present PET study were 192GBq/μmol and 638GBq/μmol respectively after a synthesis time of 32min. In monkey PET studies, the percentage difference of BPND in putamen was <3% and that in caudate was <9% for the two radioligands. The plasma protein binding was 86.2±0.3% and 85.7±0.6% for ([11C]carbonyl)raclopride and ([11C]methyl)raclopride, respectively. The radiometabolite pattern was similar for both radioligands. Conclusion: Raclopride was 11C-labeled at the carbonyl position using a palladium-mediated [11C]carbonylation reaction. A comparison between ([11C]carbonyl)raclopride and ([11C]methyl)raclopride with regard to quantitative PET outcome measurements, metabolism of radioligands and protein binding in monkey was performed. The monkey PET study with ([11C]carbonyl)raclopride showed similar results as for ([11C]methyl)raclopride. The PET studies were performed on 2 subjects. © 2015 Elsevier Inc.

Bencar AB | Date: 2012-12-19

A system (100) for controlling the environment in a reaction box (300) comprises a controller (150) configured to control a gas multiplexer (130) to switch between applying an under pressure in the reaction box (300) from a vacuum pump (140) and applying a gas flow from a connected gas source (200) to the reaction box (300) multiple times in a cyclic manner. A particle monitor (160) generates particle information representing a concentration of particles in the reaction box (300). This particle information is stored as a GMP clean room classification notification for the reaction box (300).

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