WO2005094902A2 - Agent de contraste destine a l'imagerie medicale - Google Patents

Agent de contraste destine a l'imagerie medicale Download PDF

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Publication number
WO2005094902A2
WO2005094902A2 PCT/IB2005/051021 IB2005051021W WO2005094902A2 WO 2005094902 A2 WO2005094902 A2 WO 2005094902A2 IB 2005051021 W IB2005051021 W IB 2005051021W WO 2005094902 A2 WO2005094902 A2 WO 2005094902A2
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WO
WIPO (PCT)
Prior art keywords
contrast agent
agent according
core
shell
foregoing
Prior art date
Application number
PCT/IB2005/051021
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English (en)
Other versions
WO2005094902A3 (fr
Inventor
Claus Feldmann
Original Assignee
Philips Intellectual Property & Standards Gmbh
Koninklijke Philips Electronics N. V.
Priority date (The priority date is an assumption and is not a legal conclusion. Google has not performed a legal analysis and makes no representation as to the accuracy of the date listed.)
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Application filed by Philips Intellectual Property & Standards Gmbh, Koninklijke Philips Electronics N. V. filed Critical Philips Intellectual Property & Standards Gmbh
Publication of WO2005094902A2 publication Critical patent/WO2005094902A2/fr
Publication of WO2005094902A3 publication Critical patent/WO2005094902A3/fr

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Classifications

    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
    • A61K49/00—Preparations for testing in vivo
    • A61K49/001—Preparation for luminescence or biological staining
    • A61K49/0013—Luminescence
    • C—CHEMISTRY; METALLURGY
    • C09—DYES; PAINTS; POLISHES; NATURAL RESINS; ADHESIVES; COMPOSITIONS NOT OTHERWISE PROVIDED FOR; APPLICATIONS OF MATERIALS NOT OTHERWISE PROVIDED FOR
    • C09K—MATERIALS FOR MISCELLANEOUS APPLICATIONS, NOT PROVIDED FOR ELSEWHERE
    • C09K11/00—Luminescent, e.g. electroluminescent, chemiluminescent materials
    • C09K11/08—Luminescent, e.g. electroluminescent, chemiluminescent materials containing inorganic luminescent materials
    • C09K11/77—Luminescent, e.g. electroluminescent, chemiluminescent materials containing inorganic luminescent materials containing rare earth metals
    • C09K11/7766—Luminescent, e.g. electroluminescent, chemiluminescent materials containing inorganic luminescent materials containing rare earth metals containing two or more rare earth metals
    • C09K11/7774—Aluminates
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
    • A61K49/00—Preparations for testing in vivo
    • A61K49/001—Preparation for luminescence or biological staining
    • A61K49/0063—Preparation for luminescence or biological staining characterised by a special physical or galenical form, e.g. emulsions, microspheres
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
    • A61K49/00—Preparations for testing in vivo
    • A61K49/001—Preparation for luminescence or biological staining
    • A61K49/0063—Preparation for luminescence or biological staining characterised by a special physical or galenical form, e.g. emulsions, microspheres
    • A61K49/0065—Preparation for luminescence or biological staining characterised by a special physical or galenical form, e.g. emulsions, microspheres the luminescent/fluorescent agent having itself a special physical form, e.g. gold nanoparticle
    • A61K49/0067—Preparation for luminescence or biological staining characterised by a special physical or galenical form, e.g. emulsions, microspheres the luminescent/fluorescent agent having itself a special physical form, e.g. gold nanoparticle quantum dots, fluorescent nanocrystals
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
    • A61K49/00—Preparations for testing in vivo
    • A61K49/001—Preparation for luminescence or biological staining
    • A61K49/0063—Preparation for luminescence or biological staining characterised by a special physical or galenical form, e.g. emulsions, microspheres
    • A61K49/0069—Preparation for luminescence or biological staining characterised by a special physical or galenical form, e.g. emulsions, microspheres the agent being in a particular physical galenical form
    • A61K49/0089—Particulate, powder, adsorbate, bead, sphere
    • A61K49/0091—Microparticle, microcapsule, microbubble, microsphere, microbead, i.e. having a size or diameter higher or equal to 1 micrometer
    • A61K49/0093—Nanoparticle, nanocapsule, nanobubble, nanosphere, nanobead, i.e. having a size or diameter smaller than 1 micrometer, e.g. polymeric nanoparticle
    • C—CHEMISTRY; METALLURGY
    • C09—DYES; PAINTS; POLISHES; NATURAL RESINS; ADHESIVES; COMPOSITIONS NOT OTHERWISE PROVIDED FOR; APPLICATIONS OF MATERIALS NOT OTHERWISE PROVIDED FOR
    • C09K—MATERIALS FOR MISCELLANEOUS APPLICATIONS, NOT PROVIDED FOR ELSEWHERE
    • C09K11/00—Luminescent, e.g. electroluminescent, chemiluminescent materials
    • C09K11/08—Luminescent, e.g. electroluminescent, chemiluminescent materials containing inorganic luminescent materials
    • C09K11/57—Luminescent, e.g. electroluminescent, chemiluminescent materials containing inorganic luminescent materials containing manganese or rhenium
    • C—CHEMISTRY; METALLURGY
    • C09—DYES; PAINTS; POLISHES; NATURAL RESINS; ADHESIVES; COMPOSITIONS NOT OTHERWISE PROVIDED FOR; APPLICATIONS OF MATERIALS NOT OTHERWISE PROVIDED FOR
    • C09K—MATERIALS FOR MISCELLANEOUS APPLICATIONS, NOT PROVIDED FOR ELSEWHERE
    • C09K11/00—Luminescent, e.g. electroluminescent, chemiluminescent materials
    • C09K11/08—Luminescent, e.g. electroluminescent, chemiluminescent materials containing inorganic luminescent materials
    • C09K11/74—Luminescent, e.g. electroluminescent, chemiluminescent materials containing inorganic luminescent materials containing arsenic, antimony or bismuth

Definitions

  • the present invention generally pertains to the field of medicine and optical imaging.
  • the invention provides compositions and methods for imaging cells, tissues and organs in vivo and in vitro.
  • compositions and methods are provided to enhance the imaging of tissue of throat, gullet, stomach or intestine by optical imaging techniques.
  • Medical imaging techniques have recently gained in importance in the field of diagnostics and treatment. The most important imaging techniques that are recently used are positron emission tomography (PET), single photon emission computed tomography (SPECT), magnetic resonance imaging (MRI), computed tomography (CT) and ultrasound (US). All these techniques except ultrasound imaging are characterised by a significant complexity with respect to the employed equipment. Besides the huge purchase costs of such apparatuses, the high running costs negatively influence the expenses per examination and patient.
  • optical imaging techniques involve significantly less technical and personal effort compared to the above mentioned techniques.
  • optical imaging suffers from low sensitivity which complicates a diagnosis.
  • High sensitivity means that false negative diagnoses are excluded.
  • High specificity means a reliable detection of a disease pattern, i.e. the exclusion of false positive diagnoses. It therefore remains the need for means that enhance the sensitivity and specificity of optical imaging and which are available at a reasonable price as well as easy to handle.
  • the aim of the present invention is to overcome the drawbacks of prior art and to provide compositions and methods for imaging cells, tissues and organs in vivo and in vitro at a high sensitivity and with high contrast.
  • This aim is solved by the compositions and methods according to the independent claims of the present invention, while useful embodiments are described by the features as contained in the dependent claims.
  • the invention provides a contrast agent for optical imaging comprising particles consisting of at least a core, wherein the core comprises luminescent substances absorbing and emitting electromagnetic radiation at different wavelengths.
  • the application of such a contrast agent for optical imaging techniques increases the sensitivity of the measurement.
  • the contrast agent according to the present invention is available in the form of nanoparticles, which facilitates the handling and administration thereof.
  • these active centers in the form of luminescent substances absorb and emit electromagnetic radiation at different wavelengths. This leads to a clear distinguishability between the radiation applied to the agent and the radiation obtained therefrom.
  • the luminescent substances absorb electromagnetic radiation in the wavelength range between about 350 run and about 480 nm.
  • the excitation may easily be achieved by using a GaN- or InGaN-based LED (Light Emitting Diode), which may be mounted to the end of an endoscope.
  • the light of such a source may be directed through an optical fiber to the head of an endoscope.
  • the exciting radiation in this wavelength range is identified and characterised by its blue or violet appearance. Accordingly, any light coming from the probe which is not blue or violet may be identified as some result or effect. It is thereby particularly advantageous if the exciting radiation lies in the range beneath the visible wavelength range, i.e. about 350 to 400nm. This would cause that any visible light obtained from the probe would allow the conclusion on an effect.
  • the luminescent substances preferably emit electromagnetic radiation in the wavelength range between about 480 nm and about a 750 nm. Within this range it is advantageously ensured that the emitted light is clearly distinguishable from the introduced light. The emitted light may be detected spectroscopically or, since said wavelength range lies in the visible spectrum, with the human eye.
  • the luminescent substances are formed of inorganic solids. These are easy to handle and in particular not sensitive to heat or pressure. Furthermore, inorganic solids are easy to obtain and process which makes the resulting contrast agents available at a reasonable price.
  • the luminescent substances are selected from the group consisting of the compounds and compositions as listed in table 1.
  • the contrast agent further comprises at least an optional shell around the particle core.
  • a shell By introducing a shell, different advantageous effects can be reached. Firstly, additional materials can be processed in said shell, which may be specifically effective for one or more additional imaging techniques or wavelength ranges, thus leading to the possibility of an examination using more than one imaging technique or different wavelengths for excitation or detection. Furthermore, high compatibility can be established by choosing shell material that prevents an immune reaction of the examined body against the contrast agent particles. Moreover, a shell may be established containing biological active compounds, such as antibodies, thereby supporting a favorable distribution of the contrast agent in the examined tissue.
  • At least one further shell is present, providing biocompatibility. This ensures, that after administering the contrast agent to a living organism, no immune reaction against this agent takes place, which allows the application in vivo.
  • This at least one biocompatibility shell may particularly consist of gold, SiO 2 , a polyphosphate (e.g. calcium polyphosphate), an amino acid (e.g. asparagin acid), an organic polymer (e.g.
  • a biopolymer e.g. polysaccharide, such as dextrane, xylane, glycogene, pectine, cellulose, or polypeptide, such as collagene, globuline), cysteine, or a peptide with a high amount of asparagine, or a phospholipide.
  • the expulsion of these contrast agents may furthermore take place via the kidneys if the particle diameter is small or alternatively after solvation of the solids in blood or spleen or liver.
  • the contrast agent is removed by bowel movements/stool . It is thereby preferred if at least one of the biocompatibility shells covers the core completely in order to efficiently provide biocompatibility and prevent the core from being dissolved or hydrolysed.
  • gold as shell material, some further positive effects may be achieved.
  • further active or inactive compounds may be applied and immobilised on the gold surface in an easy manner, for example by thiole linkers.
  • a thin gold layer such as the one on top of the core may under certain circumstances show an SPR (surface plasmon resonance) effect if exposed to electromagnetic radiation.
  • SPR surface plasmon resonance
  • This additional effect may be employed for the purpose of this invention, namely for the extinction and emission of certain wavelength ranges.
  • a contrast generation in certain spectral areas is enhanced. This applies in particular if the gold shell is formed of discrete gold nanoparticles attached to the surface of the core or underlying shell rather than covering the core or underlying shell in a sealing manner.
  • the particles according to the preferred embodiment may be used as contrast agent for ultrasound (US) measurements.
  • the particles thereby provide reflection capabilities for ultrasound (US) comparable to gas microbubbles as conventionally used.
  • the at least one optional shell preferably has at thickness of 1 nm to 200 nm, and more preferably 20 nm to 100 nm. It is thereby ensured that the adhesion characteristics of said shell to the core are convenient. This helps to prevent any immune reactions as well as the solvation or hydrolysis of the core.
  • the shell is formed of gold, it is particularly advantageous if the thickness lies between 1 nm and 50 nm and most preferably between 1 nm and 30 nm so that the above mentioned advantageous effects may be achieved.
  • At least one further shell is present, containing at least one antibody.
  • a specific antibody-antigene reaction can be established. This leads to specific adsorption/concentration of the contrast agent in infected tissue (e.g. cancer cells, coronar plaques).
  • infected tissue e.g. cancer cells, coronar plaques.
  • the contrast agent and the imaging process are highly specific to the respective case.
  • antibodies may be employed.
  • several examples of antibodies are given, that may be used for the described application. However, this list is not intended to be exhaustive, since other antibodies are also applicable, in particular, antibodies that are available at some future date only.
  • the contrast agent of the present invention may be used for examination of biopsates.
  • the at least one antibody is a tumor specific antibody.
  • the at least one antibody containing shell may further contain one or more proteins, preferably the HIV-tat protein. This facilitates the passage of these agents through e.g. a cell membrane. This advantageously enables examinations involving intracellular procedures and metabolisms.
  • the core of the contrast agents has a spherical, oval or lens-shape. Thereby, an optimized volume to surface ratio is provided. Furthermore, the distribution of said particles in the examined tissue or body is facilitated.
  • the core has a diameter of 1 nm to 1000 nm, preferably 50 nm to 500 nm. This comes up to the size of several proteins and bioorganic compounds as present in human and animal organisms. Thereby, these particles are easily involved in metabolism processes, as for example intercellular exchange reactions, thereby facilitating the transport and adsorption of the contrast agents at areas of interest.
  • the invention further provides pharmaceutical formulations comprising the contrast agent of the invention and a pharmaceutically acceptable excipient wherein the contrast agent is formed according to any of the above described embodiments, and wherein the formulation is suitable for administration as an imaging enhancing agent and the contrast agent is present in an amount sufficient to enhance a optical imaging image.
  • the formulations of the invention can include pharmaceutically acceptable carriers that can contain a physiologically acceptable compound that acts, e.g. to stabilize the composition or to increase or to decrease the absorption of the agent and/or pharmaceutical composition.
  • Physiologically acceptable compounds can include, for example, carbohydrates, such as glucose, sucrose, or dextrans, antioxidants, such as ascorbic acid or glutathione, chelating agents, low molecular weight proteins, compositions that reduce the clearance or hydrolysis of any co-administered agents, or excipients or other stabilizers and/or buffers.
  • Detergents can also be used to stabilize the composition or the increase or decrease the absorption of the pharmaceutical composition.
  • compositions for administration comprises a contrast agent of the invention in a pharmaceutically acceptable carrier, e.g., an aqueous carrier.
  • a pharmaceutically acceptable carrier e.g., an aqueous carrier.
  • carriers can be used, e.g., buffered saline and the like.
  • compositions may contain pharmaceutically acceptable auxiliary substances as required to approximate physiological conditions such as pH adjusting and buffering agents, toxicity adjusting agents and the like, for example, sodium acetate, sodium chloride, potassium chloride, calcium chloride, sodium lactate and the like.
  • concentration of active agent in these formulations can vary widely, and will be selected primarily based on fluid volumes, viscosities, body weight and the like in accordance with the particular mode of administration and imaging modality selected.
  • the invention may be applied according to a method for in vivo or in vitro imaging a cell, a tissue, an organ or a full body comprising the following steps: a) providing a pharmaceutical formulation comprising the contrast agent of the invention and a pharmaceutically acceptable excipient, wherein the contrast agent is formed according to any of the above described embodiments, and wherein the formulation is suitable for administration as an imaging enhancing agent and the contrast agent is present in an amount sufficient to enhance an optical imaging image; b) providing an optical imaging device or equivalent; c) administering the pharmaceutical formulation in an amount sufficient to generate the cell, tissue or body image; and d) imaging the distribution of the pharmaceutical formulation of step a) with the imaging device, thereby imaging the cell, tissue or body.
  • the pharmaceutical formulations of the invention can be administered in a variety of unit dosage forms, depending upon the particular cell or tissue or cancer to be imaged, the general medical condition of each patient, the method of administration, and the like. Details on dosages are well described on the scientific and patent literature. The exact amount and concentration of contrast agent or pharmaceutical of the invention and the amount of formulation in a given dose, or the "effective dose” can be routinely determined by, e.g. the clinician.
  • the "dosing regimen” will depend upon a variety of factors, e.g. whether the cell or tissue or tumour to be imaged is disseminated or local, the general state of the patient's health, age and the like. Using guidelines describing alternative dosing regimens, e.g.
  • compositions of the invention can be delivered by any means known in the art systematically (e.g. intra-venously), regionally or locally (e.g. intra- or peri-tumoral or intra-cystic injection, e.g. to image bladder cancer) by e.g. intra-arterial, intra-tumoral, intra-venous (iv), parenteral, intra-pneural cavity, topical, oral or local administration, as sub-cutaneous intra-zacheral (e.g. by aerosol) or transmucosal (e. g.
  • intra-arterial injections can be used to have a "regional effect", e.g. to focus on a specific organ (e.g. brain, liver, spleen, lungs).
  • intra-hepatic artery injection or intra-carotid artery injection If it is decided to deliver the preparation to the brain, it can be injected into a carotid artery or an artery of the carotid system of arteries (e.g. ocipital artery, auricular artery, temporal artery, cerebral artery, maxillary artery etc.).
  • Fig. 1 is a cross-sectional view of a particle according to the present invention.
  • This particle 1 comprises a core 2, optionally covered by shells 3 to 4.
  • the core 2 comprises a luminescent solid as described above.
  • the core 2 can be excited with 350 to 480 nm light of, for instance, a GaN- or InGaN-based light emitting diode.
  • a diode can be located on the top-end of an endoscope, or the light can be sent via a glass fiber to the top-end of an endoscope.
  • the luminescent core 2 While being excited, the luminescent core 2 emits visible light which is with a different wavelength compared to the incoming light. The emitted light can be detected endoscopically via spectroscopic measures or via the human eye.
  • a first optional shell 3 is applied on top of the core 2. This optional shell 3 mainly serves to provide biocompatibility and is built of for example dextrane.
  • shell 3 covers the core completely and has a thickness greater than 1 nm. Additionally, if shell 3 covers the core completely it may serve to prevent the core from being dissolved or hydrolysed, for instance by applying SiO 2 . Optionally, shell 3 can also contain nanoscale gold particles, which may serve as linkers to e.g. thiol functionalities of a biopolymer or antibody and/or as an antenna for incoming light.
  • a second optional shell 4 is applied which contains a suitable antibody. This antibody containing shell 4 does not cover the core completely. It causes that the contrast agent will be attached specifically to infected tissue due to a specific antibody-antigen interaction of the antibodies.
  • the optional antibody containing shell 4 allows to diagnose cancel infected tissue, in particular of throat, gullet, stomach or intestine.
  • Example 1 5,5 g Zn(CH 3 COO) 3 x 2H 2 O, 8,8 g GaCl 3 , 11 ,4 g thiourea and 67 mg
  • Mn(CH 3 COO) 2 x 2H 2 O are suspended in 50ml diethylenglycole. The suspension is stirred steadily and heated to 190°C for 2 hours. A suspension is obtained which contains nanoscaled ZnGa 2 S :Mn with a particle diameter of about 90 nm. After cooling down, the ZnGa2S 4 :Mn-particles may be separated from the primary suspension by centrifugation, followed by suitable washing processes (e.g. repeated resuspending of the solid in ethanol and/or acetone, repeated centrifugation) and transferred to an aqueous suspension (e.g. isotonic solution or phosphate buffer).
  • suitable washing processes e.g. repeated resuspending of the solid in ethanol and/or acetone, repeated centrifugation
  • an aqueous suspension e.g. isotonic solution or phosphate buffer.
  • the nanoscaled ZnGa 2 S 4 :Mn-particles may be further modified.
  • 10 ml of an aqueous solution, containing 0,2 g cysteine and 1,5 tetraethylorthosilicate may be added.
  • a cysteine containing shell of SiO 2 may be built on top of the phosphor material.
  • the thickness of this shell amounts approximately 30 nm.
  • hystidine-modified pemtumomab may be added and the antibody may be attached to the cysteine/SiO 2 - layer by amide-bridging as a first shell.
  • the product may be used as contrast agent for optical imaging.
  • 1,2 g Ca(CH 3 COO) 2 x H 2 O and 23 mg BiCl 3 are suspended in 50 ml diethylenglycole. The suspension is stirred steadily and heated to 190°C. At this temperature 1,2 g Na 2 SO 4 dissolved in 20 ml diethylenglycole are added. Thereafter, the solution is heated at 190°C for 2 hours.
  • a suspension which contains nanoscaled CaSO 4 :Bi with a particle diameter of about 60 nm.
  • a solution of 1,3 g NaAuCl 4 x 2H 2 O in water is added at 180°C during a period of time of 1 hour.
  • nanoscale gold particles are precipitated and adhered on the surface of CaSO 4 :Bi.
  • the gold particles are about 5 to 10 nm in diameter.
  • the gold covered CaSO 4 :Bi-particles may be separated from the primary suspension by centrifugation, followed by suitable washing processes (e.g. repeated resuspending of the solid in ethanol and/or acetone, repeated centrifugation) and transferred to an aqueous suspension (e.g.
  • the nanoscaled gold covered CaSO :Bi-particles may be further modified.
  • 10 ml of an aqueous solution, containing 0,2 g cysteine and 1,5 tetraethylorthosilicate may be added.
  • a cysteine containing shell of SiO 2 may be built on top of the gold shell. The thickness of this shell amounts to approximately 30 nm.
  • hystidine-modified pemtumomab may be added and the antibody may be attached to the cysteine/SiO 2 -layer by amide- bridging as a second shell.
  • the product may be used as contrast agent for optical imaging. Due to the gold layer, the contrast agent may further be employed in ultrasound (US) measurements.
  • Example 3 1,00 g Al(OCH(CH 3 ) 2 ) 3 , 0,78 g Y(OCH(CH 3 ) 2 ) 3 and 10 mg Ce(CH 3 COO) x H 2 O are suspended in 50 ml diethylenglycole. The suspension is stirred steadily and heated to 140°C. 0,5 ml of a 2-molar caustic soda are added.
  • a suspension is obtained containing nanoscaled Y 3 Al 5 Oi 2 :Ce with a particle diameter of approximately 30 nm.
  • the nanoscaled particles may be separated from the primary suspension and transferred to a aqueous suspension (i.g. isotonic solution or phosphate buffer).
  • a aqueous suspension i.g. isotonic solution or phosphate buffer.
  • 10 ml of an aqueous solution containing 50 ml asparagine acid and 100 mg tetraethylorthosilicate may be added to the suspensions over a time span of 1 hour, respectively.
  • an asparagine acid containing shell of SiO 2 may be built upon the nanoparticles.
  • the thickness of this shell amounts to approximately 15 nm.
  • 2 ml of an aqueous 10 "4 molar solution of an antibody e.g. cetuximab or a histidine modified antibody (e.g. histidine modified cetuximab) may be added and the antibody may be attached to the asparagine acid/SiO 2 -layer by amide bridging as a second shell.
  • the product may be used as a contrast agent for optical imaging.
  • the invention has been described herein with reference to certain preferred embodiments. However, as obvious variations thereon will become apparent to those skilled in the art, the invention is not to be considered as limited thereto. In particular, other combinations and preparations of metal oxides than described in one of the examples may serve as contrast agents according to the present invention.
  • the given examples of antibodies that may be used according to the present invention are not intended to be exhaustive, since other antibodies are also applicable, in particular, antibodies that are available at some future date only. Any reference signs in the claims do not limit the scope of the invention.
  • the term is to be understood as not excluding other elements or steps and the term hearinga" orpatian" does not exclude a plurality.

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  • Chemical & Material Sciences (AREA)
  • Health & Medical Sciences (AREA)
  • Engineering & Computer Science (AREA)
  • Inorganic Chemistry (AREA)
  • Materials Engineering (AREA)
  • Epidemiology (AREA)
  • Biomedical Technology (AREA)
  • Organic Chemistry (AREA)
  • Life Sciences & Earth Sciences (AREA)
  • Animal Behavior & Ethology (AREA)
  • General Health & Medical Sciences (AREA)
  • Public Health (AREA)
  • Veterinary Medicine (AREA)
  • Nanotechnology (AREA)
  • Medicines Containing Antibodies Or Antigens For Use As Internal Diagnostic Agents (AREA)
  • Luminescent Compositions (AREA)

Abstract

L'invention concerne un agent de contraste destiné à l'imagerie optique comprenant des particules (1) comprenant au moins un noyau (2), ledit noyau comprenant des substances luminescentes qui absorbent et émettent un rayonnement électromagnétique à des longueurs d'ondes différentes.
PCT/IB2005/051021 2004-04-01 2005-03-24 Agent de contraste destine a l'imagerie medicale WO2005094902A2 (fr)

Applications Claiming Priority (2)

Application Number Priority Date Filing Date Title
EP04101351 2004-04-01
EP04101351.7 2004-04-01

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Publication Number Publication Date
WO2005094902A2 true WO2005094902A2 (fr) 2005-10-13
WO2005094902A3 WO2005094902A3 (fr) 2006-05-26

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Cited By (6)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
EP1920784A1 (fr) * 2006-11-13 2008-05-14 Koninklijke Philips Electronics N.V. Sensibilisateurs de radiation pour la thérapie par rayonnements ionisants et pour l'imagerie
WO2009024372A1 (fr) * 2007-08-20 2009-02-26 Sustech Gmbh & Co. Kg Matériaux composites luminescents
CN104178160A (zh) * 2013-05-22 2014-12-03 海洋王照明科技股份有限公司 铈铽双掺杂氮硅镧发光材料、制备方法及其应用
WO2015042256A1 (fr) * 2013-09-18 2015-03-26 Caliper Life Sciences Imagerie d'espèces réactives in vivo
WO2015126722A1 (fr) * 2014-02-24 2015-08-27 Google Inc. Particules mises au point avec commande de contraste de polarisation et d'alignement pour une imagerie améliorée
WO2022039312A1 (fr) * 2020-08-19 2022-02-24 국민대학교산학협력단 Nanoparticules et composition pour imagerie biologique basée sur l'atténuation des rayons x

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US5893999A (en) * 1993-09-13 1999-04-13 Kabushiki Kaisha Toshiba Ultrafine inorganic phosphor, specifically binding material labeled with this phosphor, and detection method using this specific binding material
US6699723B1 (en) * 1997-11-25 2004-03-02 The Regents Of The University Of California Organo luminescent semiconductor nanocrystal probes for biological applications and process for making and using such probes
WO2001086299A2 (fr) * 2000-05-05 2001-11-15 Bayer Aktiengesellschaft Nanoparticules dopees servant de marqueurs biologiques
WO2003037788A1 (fr) * 2001-11-01 2003-05-08 Oxonica Limited Nanoparticules luminescentes hydrosolubles
WO2003038011A2 (fr) * 2001-11-01 2003-05-08 Oxonica Limited Nanomateriaux luminescents
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