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X-ray and gama-photon activable organic compounds, their preparation and their uses

Référence

03306-02

Statut des brevets

Priority patent application EP10290323.4 filed on June 15th, 2010 entitled “Energy Dispersive X-Ray Activation (EDIXA) of organic Probes (Caged Compounds)”

Inventeurs

Morgane PETIT
Peter DALKO
David OGDEN
Guillaume BORT
Cécile SICARD

Statut commercial

Exclusive or non-exclusive licenses, Collaborative agreement

Laboratoire

Laboratoire de Chimie et Biochimie Pharmacologiques et Toxicologiques, (UMR 8601, CNRS) Université Paris Descartes, Paris, France, http://www.biomedicale.parisdescartes.fr/umr8601

Description

CONTEXT

The selective activation of compounds in inaccessible (body)spaces is of a central interest in therapy, and also in material sciences. Light activation of inert precursors were developed earlier for the liberation of biologically active substrates in high spatial resolution. As the penetration of light in tissues is limited to depths of around 100 μm even with near-IR wavelengths the scope of light activation in deep tissue is limited. Although the use of fiber optics, implantable photoelectrodes or laser coupled microelectrode arrays and icromechanical systems may solve part of the problems, the release of substrates with high stereospatial control in otherwise inaccessible spaces remains a challenge.

TECHNICAL DESCRIPTION

The invention describes a novel type of activation with a new class of devices that respond to X-ray, or, gamma activation, and allow the liberation of compounds in otherwise inaccessible spaces in high spatio-temporal control. The device has the capacity masking the biological activity of a given compound, that can be released by X-ray, or, gamma activation. The central element of the photodevice is a quinoline-derived protecting group having tethered gadolinium(III) sensitizer that allows converting part of the X-ray, or, gamma photon energy to productive chemistry. Noteworthy, the distribution of the device can be followed (imaged) by current MRI technics in living systems.

BENEFITS

The method has the potential to apply in medical treatment and also in material sciences where the liberation of compouns is demanded in high resolution in otherwise unaccessible (body)spaces. When applied in therapy the method has the potential diminishing the general toxicity of the attached biologically active substrate and excerce activity within a spatially restricted area.

INDUSTRIAL APPLICATIONS

The most obvious application of this approach seems to be in cancer chemotherapy. Stereotaxic tools that permit some degree of localized X-ray or γ-ray irradiation (to approximately 6 mm) already exist in cancer therapy and would combine well with the proposed approach to increase the effectiveness and minimize local damage during radiotherapy (Gamma Knife, CyberKnife system, and Novalis). As well as utilizing the ability of x-rays to penetrate biological tissue, the probes themselves are opaque to MRI and other imaging methods, allowing their distribution to be monitored.

DEVELOPMENT STAGE

The proof of principle was demonstrated under in vitro conditions ; the optimization of the device under in vivo conditions is underway.

For further information, please contact us (Ref 03306-02)

 


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