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Hyperpolarized Biosensors in Molecular Imaging

Fact Sheet

Reporting

Results

Objective

Xenon biosensors have an outstanding potential to increase the significance of magnetic resonance imaging (MRI) in molecular imaging and to combine the advantages of MRI with the high sensitivity of hyperpolarized Xe-129 and the specificity of a functionalized contrast agent. Based on new detection schemes (Hyper-CEST method) in Xe MRI, this novel concept in molecular diagnostics will be made available for biomedical applications. The advancement focuses on high-sensitivity in vitro diagnostics for localization of tumour cells in cell cultures and first demonstrations on animal models based on a transferrin-functionalized biosensor. Such a sensor will enable detection of subcutaneous tumours at high sensitivity without any background signal. More detailed work on the different available Hyper-CEST contrast parameters focuses on an absolute quantification of new molecular markers that will improve non-invasive tumour diagnostics significantly. NMR detection of functionalized Xe biosensors have the potential to close the sensitivity gap between modalities of nuclear medicine like PET/SPECT and MRI without using ionizing radiation or making compromises in penetration depth like in optical methods.

Programme(s)

FP7-IDEAS-ERC - Specific programme: "Ideas" implementing the Seventh Framework Programme of the European Community for research, technological development and demonstration activities (2007 to 2013)

Topic(s)

ERC-SG-LS7 - Applied life sciences, biotechnology and bioengineering: agricultural, animal, fishery, forestry/food sciences; biotechnology, chemical biology, genetic engineering, synthetic biology, industrial biosciences; environmental biotechnology.

Call for proposal

ERC-2009-StG

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Funding Scheme

ERC-SG - ERC Starting Grant

Principal Investigator

Leif Schröder (Dr.)

Host institution

FORSCHUNGSVERBUND BERLIN EV

Address

Rudower Chaussee 17
12489 Berlin

Germany

Activity type

Higher or Secondary Education Establishments

EU Contribution

€ 1 848 600

Website

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Principal Investigator

Leif Schröder (Dr.)

Administrative Contact

Anne Höner (Dr.)

Beneficiaries (1)

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FORSCHUNGSVERBUND BERLIN EV

Germany

EU Contribution

€ 1 848 600

Project information

BIOSENSORIMAGING

Grant agreement ID: 242710

Status

Closed project

Start date

1 December 2009
End date

30 November 2014

Funded under:

FP7-IDEAS-ERC

Overall budget:

€ 1 848 600
EU contribution

€ 1 848 600

Hosted by:

FORSCHUNGSVERBUND BERLIN EV

Germany

Final Report Summary - BIOSENSORIMAGING (Hyperpolarized Biosensors in Molecular Imaging)

Basic research has made significant progress in understanding many diseases on a molecular level and triggered the field of molecular imaging and novel targeted drug delivery approaches. Both can be summarized in the concept of “personalized medicine” based on the identification of multiple molecular markers and the delivery of functionalised drug carriers. Techniques for imaging the spatial distribution of such markers and monitoring drug delivery in a living organism are therefore a highly sought-after goal in order to enable early diagnosis and individualized therapy. Nuclear magnetic resonance (NMR), as used for diagnostic imaging, has an outstanding molecular specificity but suffers from low sensitivity. It could contribute significantly to revealing disease-specific markers and implementing the aim of personalized medicine, while being non-invasive and abstaining from using problematic ionizing radiation. Therefore, solving the sensitivity problem of NMR is of major interest for improving early disease detection and optimized monitoring of therapy. The ERC project BiosensorImaging implemented a novel approach to boost the sensitivity of NMR imaging for biomedical applications.
Important improvements have been achieved in the production of laser-polarized xenon, in particular its stability in continuous-flow setups where the gas is used in repetitive delivery for ultra-sensitive detection of targeted xenon hosts in nanomolar concentration ranges. The shot-to-shot noise for gas delivery could be decreased to <0.5% by improved polarizer design. The project also made significant contributions for image encoding procedures within the emerging field of CEST detection (chemical exchange saturation transfer). Optimized use of the available magnetization now allows for snap-shot imaging of nanomolar concentrations – a regime that would require acquisition times of ca. 1100 years with conventional detection techniques.
Following development of the image preparation and acquisition steps, another important component was the development of an NMR-compatible bioreactor that allowed demonstration of xenon NMR studies in live cells. This served as a stepping stone for future biomedical applications in living organisms but also to optimize biosensor design for various molecular targets. An initial study demonstrated untargeted labelling of cells with functionalized xenon. This important intermediate step served as proof for sufficient sensitivity under physiological conditions. With the new tools on hand, the project focused on the development of targeted sensors with biological relevance. We implemented various strategies to use individual xenon hosts (such as cryptophane cages) for the design of targeted contrast agents. These include antibody-based modular approaches with dual-mode reporters (NMR/fluorescence), lipopeptide-functionalized liposomes, and metabolic oligosaccharide engineering (MOE). The MOE approach in particular was considered as a seminal step forward since it could not be realized with other MRI approaches so far.
For advancing the technique further to in vivo applications, we tested alternative xenon hosts, amongst them clinically approved nanodroplets with superior gas-binding properties. This allowed us to demonstrate the first multi-channel MRI of hyperpolarized xenon based on different nanocarriers with unprecedented sensitivity. The project also made important contributions to understand the behavior of functionalized xenon in phospholipid membrane material. This will help to design optimized liposomal carriers for xenon MRI applications and fostered further studies on membrane fluidity and integrity which will be used in studies on antimicrobial peptides.
In summary, BiosensorImaging has contributed significantly to advance the field of xenon MRI and to make it part of the molecular imaging tool box for future applications in improved drug development and therapy monitoring where it is envisioned to close the sensitivity gap between NMR and PET for improved diagnostic imaging.

Project information

BIOSENSORIMAGING

Grant agreement ID: 242710

Status

Closed project

Start date

1 December 2009
End date

30 November 2014

Funded under:

FP7-IDEAS-ERC

Overall budget:

€ 1 848 600
EU contribution

€ 1 848 600

Hosted by:

FORSCHUNGSVERBUND BERLIN EV

Project information

BIOSENSORIMAGING

Grant agreement ID: 242710

Status

Closed project

Start date

1 December 2009
End date

30 November 2014

Funded under:

FP7-IDEAS-ERC

Overall budget:

€ 1 848 600
EU contribution

€ 1 848 600

Hosted by:

FORSCHUNGSVERBUND BERLIN EV

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Last update: 25 May 2017

Record number: 92855

CORDIS

Objective

Principal Investigator

Host institution

Beneficiaries (1)

Project information

Final Report Summary - BIOSENSORIMAGING (Hyperpolarized Biosensors in Molecular Imaging)

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CORDIS

Objective

Principal Investigator

Host institution

Beneficiaries (1)

Project information

Final Report Summary - BIOSENSORIMAGING (Hyperpolarized Biosensors in Molecular Imaging)

Project information

Deliverables

Publications

Project information

Project information

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