Koninklijke Philips Corporation N.v.

Koninklijke Philips Electronics N.v.

Philips Intellectual Property & Standards Gmbh

Holger Gruell

Sander Langereis

Johan Lub

Rene Theodorus Wegh

Jeroen Alphons Pikkemaat

Rudolf Mathias Johannes Nicolaas Lamerichs

Nicolaas Petrus Willard

Anke De Vries

Erica Maria Gerarda Aussems-Custers

Jochen Keupp

Tobias Richard Schaeffter

Dirk Burdinski

Edwin Heijman

Danielle Beelen

Muhammed Yildirim

Mariska De Smet

Erica M G Aussems-Custers

Ulrich Katscher

Sin Yuin Yeo

Rudolf M J N Lamerichs

Tobias Schaeffter

Described are drug carriers useful in magnetic resonance imaging (MRI)-guided drug release comprising a shell capable of releasing an enclosed biologically active agent as a result of a local stimulus, e.g. energy input, such as heat, wherein the shell encloses aF MR contrast agent. Preferably, the carrier also acts as a contrast enhancement agent for MRI based on the principle of Chemical Exchange-dependent Saturation Transfer (CEST). To this end the shell encloses a cavity that comprises a paramagnetic chemical shift reagent, a pool of proton analytes, and theF contrast agent, and wherein the shell allows diffusion of the proton analytes.

Drug carrier providing MRI contrast enhancement

Described are amphiphilic polymers that are provided with chelating moieties. The amphiphilic polymers are block copolymers comprising a hydrophilic block and a hydrophobic block, with the chelating moieties linked to the end-group of the hydrophilic block. The disclosed polymers are capable of self-assembly into structures such as micelles and polymersomes. With suitable metals present in the form of coordination complexes with the chelating moieties, the chelating amphiphilic polymers of the invention are suitable for use in various imaging techniques requiring metal labeling, such as MRI (T/Tweighted contrast agents or CEST contrast agents) SPECT, PET or Spectral CT.

Chelating amphiphilic polymers

Disclosed are carriers for drugs and/or MR imaging agents having a lipid bilayer shell comprising a phospholipid having two terminal alkyl chains, one being a short chain having a chain length of at most seven carbon atoms, the other being a long chain having a chain length of at least fifteen carbon atoms. The mixed long/short chain phospholipids serve to tune the release properties of the carrier. Preferred phospholipids are phosphatidylcholines.

Lipid bilayer carrier for drugs or imaging agents

Disclosed are lipidomimetic compounds of formula I (I) wherein: G represents a group satisfying formula II: HO&#x2014;CH&#x2014;{CH(OH)&#x2014;CH-0}-CH&#x2014;{C(=0)-0-CH})&#x2014; formula II each n independently is an integer from 1-30; m is an integer from 1-10; q is 0 or 1. These compounds can be added to the lipid bilayer of thermosensitive liposomes, for the purpose of aiding in the prevention of leakage of the liposomes' contents at 37&#xb0; C., and retarding clearance from circulation. 

Lipidomimetic compounds and uses thereof

Described are amphiphilic polymers that are provided with chelating moieties. The amphiphilic polymers are block copolymers comprising a hydrophilic block and a hydrophobic block, with the chelating moieties linked to the end-group of the hydrophilic block. The disclosed polymers are capable of self-assembly into structures such as micelles and polymersomes. With suitable metals present in the form of coordination complexes with 5 the chelating moieties, the chelating amphiphilic polymers of the invention are suitable for use in various imaging techniques requiring metal labeling, such as MRI (T 1/T 2 weighted contrast agents or CEST contrast agents) SPECT, PET or Spectral CT.

The invention provides MRI contrast agents which provide a high sensitivity and which have an optimised body retention time. These agents enable the mapping of the local pH, temperature, oxygen concentration or other metabolites in a patient's body by the use of Chemical Exchange Saturation Transfer (CEST). Particularly pH and temperature mapping are useful for the detection of small cancer lesions and localized inflammation respectively.

Responsive MRI contrast agents

A method for MRI imaging to obtain information about a local physiochemical parameter after administration to a patient of a contrast agent including at least one non-responsive contrast enhancing entity that does not occur naturally in a human body and at least one responsive contrast enhancing entity attached to or mixed with the non-responsive contrast enhancing entity. By using such non-responsive contrast enhancing entities, a value for the physicochemical parameter can be obtained by acquiring only three images, providing a method which will be easier to apply in a clinical routine, since it will be faster and less sensitive to motion or flow artifacts.

Elimination of contrast agent concentration dependency in MRI

The present invention provides a method MRI imaging. By applying a time modulation to the contrast enhancement of an MRI contrast agent, the method according to the invention leads to images with improved signal-to-noise ratio in the contrast-enhanced areas, strongly suppressed unwanted signal in the unenhanced areas, and reduced artefacts, such as motion artefacts.

MRI involving contrast agent with time modulated contrast enhancement

Magnetic resonance monitoring of a target () uses the detected magnetic resonance to determine movement such as diffusion of contrast agent relative to the object, and uses the movement to discriminate () a part of the contrast agent which is bound to the target, from the rest of the contrast agent. The need for clearing agents can be avoided or reduced, and hence imaging is instantaneous. A 'stationary spin map' of the object can be formed by comparing the movements in the different directions, and determining if the differences between them are less than a given threshold. Determining isotropic movement in this way for a number of locations on the object allows the map to be generated.

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Eindhoven, Netherlands

Holger Gruell