DE3744518A1 - Ferromagnetic antibodies for contrast enhancement of in vivo magnetic resonance imaging - Google Patents

Ferromagnetic antibodies for contrast enhancement of in vivo magnetic resonance imaging

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Publication number
DE3744518A1
DE3744518A1 DE19873744518 DE3744518A DE3744518A1 DE 3744518 A1 DE3744518 A1 DE 3744518A1 DE 19873744518 DE19873744518 DE 19873744518 DE 3744518 A DE3744518 A DE 3744518A DE 3744518 A1 DE3744518 A1 DE 3744518A1
Authority
DE
Germany
Prior art keywords
ferromagnetic
antibodies
magnetic resonance
resonance imaging
contrast enhancement
Prior art date
Legal status (The legal status 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 status listed.)
Withdrawn
Application number
DE19873744518
Other languages
German (de)
Inventor
Andreas Dr Med Dr Rer Bockisch
Peter Oehr
Current Assignee (The listed assignees may be inaccurate. Google has not performed a legal analysis and makes no representation or warranty as to the accuracy of the list.)
BOCKISCH ANDREAS
Original Assignee
BOCKISCH ANDREAS
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.)
Filing date
Publication date
Application filed by BOCKISCH ANDREAS filed Critical BOCKISCH ANDREAS
Priority to DE19873744518 priority Critical patent/DE3744518A1/en
Publication of DE3744518A1 publication Critical patent/DE3744518A1/en
Withdrawn legal-status Critical Current

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Classifications

    • AHUMAN NECESSITIES
    • A61MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61KPREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
    • A61K49/00Preparations for testing in vivo
    • A61K49/06Nuclear magnetic resonance [NMR] contrast preparations; Magnetic resonance imaging [MRI] contrast preparations
    • A61K49/18Nuclear magnetic resonance [NMR] contrast preparations; Magnetic resonance imaging [MRI] contrast preparations characterised by a special physical form, e.g. emulsions, microcapsules, liposomes
    • A61K49/1818Nuclear magnetic resonance [NMR] contrast preparations; Magnetic resonance imaging [MRI] contrast preparations characterised by a special physical form, e.g. emulsions, microcapsules, liposomes particles, e.g. uncoated or non-functionalised microparticles or nanoparticles
    • A61K49/1821Nuclear magnetic resonance [NMR] contrast preparations; Magnetic resonance imaging [MRI] contrast preparations characterised by a special physical form, e.g. emulsions, microcapsules, liposomes particles, e.g. uncoated or non-functionalised microparticles or nanoparticles coated or functionalised microparticles or nanoparticles
    • A61K49/1824Nuclear magnetic resonance [NMR] contrast preparations; Magnetic resonance imaging [MRI] contrast preparations characterised by a special physical form, e.g. emulsions, microcapsules, liposomes particles, e.g. uncoated or non-functionalised microparticles or nanoparticles coated or functionalised microparticles or nanoparticles coated or functionalised nanoparticles
    • A61K49/1827Nuclear magnetic resonance [NMR] contrast preparations; Magnetic resonance imaging [MRI] contrast preparations characterised by a special physical form, e.g. emulsions, microcapsules, liposomes particles, e.g. uncoated or non-functionalised microparticles or nanoparticles coated or functionalised microparticles or nanoparticles coated or functionalised nanoparticles having a (super)(para)magnetic core, being a solid MRI-active material, e.g. magnetite, or composed of a plurality of MRI-active, organic agents, e.g. Gd-chelates, or nuclei, e.g. Eu3+, encapsulated or entrapped in the core of the coated or functionalised nanoparticle
    • A61K49/1875Nuclear magnetic resonance [NMR] contrast preparations; Magnetic resonance imaging [MRI] contrast preparations characterised by a special physical form, e.g. emulsions, microcapsules, liposomes particles, e.g. uncoated or non-functionalised microparticles or nanoparticles coated or functionalised microparticles or nanoparticles coated or functionalised nanoparticles having a (super)(para)magnetic core, being a solid MRI-active material, e.g. magnetite, or composed of a plurality of MRI-active, organic agents, e.g. Gd-chelates, or nuclei, e.g. Eu3+, encapsulated or entrapped in the core of the coated or functionalised nanoparticle coated or functionalised with an antibody

Abstract

Specific antibodies accumulate in their target tissue after administration (i.v., intraperitoneal, intrapleural, etc.). The antibodies described herein are associated with ferromagnetic particles which thus likewise accumulate in the target tissue. The particles lead to an increased rate of relaxation in magnetic resonance imaging investigations and thus to a targeted increase in contrast of the pathological process.

Description

Gattung des Anmelde­ gegenstandesGenre of registration object

Die Erfindung betrifft einen ferromagneti­ schen Antikörper zur Kontrastverstärkung in der in vivo Kernspintomographie nach dem Oberbegriff des Anspruchs 1.The invention relates to a ferromagneti antibodies for contrast enhancement in in vivo magnetic resonance imaging the preamble of claim 1.

Angaben zur GattungInformation on the genus

Die ferromagnetischen Antikörper zur Kon­ trastverstärkung in der in vivo Kern­ spintomographie werden zur spezifischen Darstellung von pathologischen Prozessen beim Menschen eingesetzt. Ferromagneti­ sche Partikel sind mit Antikörpern bela­ den, die sich entsprechend der Eigen­ schaften der Antikörper im Zielgewebe anreichern. Die Ferromagnete führen zu einer erheblichen Verkürzung der Relaxa­ tionszeiten T 1 und T 2 im Zielgewebe.The ferromagnetic antibodies for contrast enhancement in in vivo nuclear spin tomography are used for the specific representation of pathological processes in humans. Ferromagnetic particles are loaded with antibodies that accumulate in the target tissue according to the properties of the antibodies. The ferromagnets lead to a considerable reduction in the relaxation times T 1 and T 2 in the target tissue.

Stand der TechnikState of the art

In der Kernspintomographie werden seit einiger Zeit paramagnetische Relaxati­ onsbeschleuniger (ungekoppelt) einge­ setzt. Ebenfalls ungekoppelte ferroma­ gnetische Partikel wurden versuchsweise zur Darstellung des Gastrointestinal­ traktes oder der Leber eingesetzt. Spe­ zifische Antikörper zur Lokalisation pa­ thologischer Prozesse werden in der Nuk­ learmedizin als radioaktiv markierte An­ tikörper verwendet (Radioimmunszintigra­ phie).Magnetic resonance imaging has been used since some time paramagnetic relaxati ons accelerator (uncoupled) switched on puts. Also uncoupled ferroma Magnetic particles were tried to represent the gastrointestinal tractes or the liver used. Spe specific antibodies for localization pa thological processes are in the nuc lear medicine marked as radioactive antibody used (radioimmunosintintra phie).

Kritik des Standes der TechnikCriticism of the state of the technology

Die Kopplung paramagnetischer Substanzen an Antikörper führt zu keinem Erfolg, da der erzielbare Effekt wegen der zu nie­ drigen Konzentration der Antikörper im Zielgewebe bei weitem nicht ausreichend ist.The coupling of paramagnetic substances of antibodies leads to no success because the achievable effect because of the never concentration of antibodies in the Target tissue is far from sufficient is.

Die Radioimmunszintigraphie wird durch die beschränkte räumliche Auflösung der nuklearmedizinischen Abbildungssysteme (Scanner, Gammakamera, SPECT) behindert. Ferner führt der Einsatz der radioakti­ ven Markierungsisotope zu einer Strah­ lenbelastung des Patienten.The radioimmunoscintigraphy is by the limited spatial resolution of the nuclear medical imaging systems (Scanner, gamma camera, SPECT) disabled. Furthermore, the use of radioakti ven marking isotopes to a beam load on the patient.

Aufgabetask

Kontrastveränderung mittels markierter Antikörper bei der Kernspintomographie innerhalb pathologischer Prozesse.Contrast change using marked Antibodies in magnetic resonance imaging within pathological processes.

Lösungsolution

Ferromagnetische Partikel werden mit spezifischen Antikörpern beladen. Ferromagnetic particles are with specific antibodies.  

Weitere Ausgestaltung der ErfindungFurther configuration the invention

Die Partikel, z. B. Magnetit, müssen für die i. v. Applikation ausreichend klein sein, um das RES passieren zu können. Eine Partikelgröße deutlich unter 1 um ist somit erforderlich. Für andere An­ wendungen, z. B. die intraperitonaeale Applikation entfällt diese Beschränkung.The particles, e.g. B. magnetite, need for the i. v. Application sufficiently small to be able to pass the RES. A particle size well below 1 µm is therefore necessary. For others phrases, e.g. B. the intraperitonaeal Application does not have this limitation.

Erzielbare VorteileAchievable advantages

Die ferromagnetischen Antikörper konzen­ trieren sich im Zielgewebe und führen dort zu einer Relaxationsbeschleunigung bei der Kernspintomographie und somit zu einer besseren Kontrastierung des patho­ logischen Prozesses.Concentrate the ferromagnetic antibodies are in the target tissue and lead there to an acceleration of relaxation in magnetic resonance imaging and thus too a better contrast of the patho logical process.

AusführungsbeispielEmbodiment

Drei Beispiele seien hier explizit aufgeführt:Three examples are explicit here listed:

  • 1. Das ferromagnetische Partikel wird mit einem Antikörper (Carrier) konju­ giert, über Säulenchromatographie gerei­ nigt und am histochemischen Schnitt quali­ tativ auf biologische Aktivität unter­ sucht.1. The ferromagnetic particle is with an antibody (carrier) konju yawed, column chromatography nig and qualified at the histochemical section tative to biological activity looking for.
  • 2. Das ferromagnetische Partikel wird sekundär eingeführt. Es wird an einen Träger konjugiert, der mit einem Teil des Antikörpers reagieren kann. Hierzu eignet sich z. B. eine Substanz, die an den Fc-Teil des Antikörpers bindet. Zu diesem Zweck müßte das magnetische Par­ tikel mit dem Fc-bindenden Teil vor In­ jektion des Antikörpers zusammengebracht werden. Diese Methode hat den Vorteil, daß eine ferromagnetische Markierung an beliebige Antikörper gebracht werden kann. Das Konjugat aus Antikörper und ferromagnetischem, Fc-bindendem Teil kann in vivo angewendet werden und rei­ chert sich in seinem Zielgewebe bzw. -organ an.2. The ferromagnetic particle is introduced secondarily. It is going to one Carrier conjugated to one part of the antibody can react. For this is suitable for. B. a substance that binds the Fc part of the antibody. To for this purpose the magnetic par article with the Fc-binding part before In injection of the antibody will. This method has the advantage that a ferromagnetic mark on any antibodies can be brought can. The antibody and conjugate ferromagnetic, Fc-binding part can be used in vivo and rei secures itself in its target tissue or -organ on.
  • 3. Der Antikörper wird mit einer Sub­ stanz konjugiert, die hohe Affinität zu anderen Substanzen hat. In diesem Falle würde man zuerst den Antikörper appli­ zieren und die mit dem Konjugat reagie­ rende, auf ein ferromagnetisches Parti­ kel aufgebrachte Substanz erst danach, wenn der Antikörper bereits gebunden hat. Auch in diesem Fall kann man eine Ferromagnetmarkierung für beliebige An­ tikörper einsetzen. Da man in diasem Fall Substanzen mit höherer Affinität, als sie der Antikörper besitzt, einset­ zen kann, hat diese Methode für diagno­ stische Zwecke den Vorteil, daß in rela­ tiv kurzer Zeit eine hohe Anreicherung der magnetisierbaren Partikel im Zielge­ webe bzw. -organ erreicht wird, was ei­ nen geringeren Blutpoolhintergrund zur Folge hat.3. The antibody is treated with a sub punch conjugate, the high affinity to other substances. In this case one would first appli the antibody decorate and react with the conjugate to a ferromagnetic part only applied substance afterwards, if the antibody is already bound Has. In this case too, one can Ferromagnetic marking for any type insert the body. Since you are in diasem Case substances with higher affinity, when it has the antibody zen has this method for diagno tical purposes the advantage that in rela high accumulation in a short time of the magnetizable particles in the target area webe or organ is achieved, what egg lower blood pool background Consequence.

Claims (2)

OberbegriffGeneric term Ferromagnetische Antikörper zur Kon­ trastverstärkung in der in vivo Kern­ spintomographie Kennzeichnender Teil Ferromagnetic antibodies to Kon contrast enhancement in the in vivo core spin tomography Characteristic part Dadurch gekennzeichnet, daß sich die ferromagnetischen Antikörper spezifisch anreichern und die Relaxation der Kern­ spins ihrer Umgebung beschleunigen (T 1, T 2 verkürzen). Characterized in that the ferromagnetic antibody specifically accumulate and the relaxation of the nuclear spins around its speed (T 1, T 2 shorten).
DE19873744518 1987-12-30 1987-12-30 Ferromagnetic antibodies for contrast enhancement of in vivo magnetic resonance imaging Withdrawn DE3744518A1 (en)

Priority Applications (1)

Application Number Priority Date Filing Date Title
DE19873744518 DE3744518A1 (en) 1987-12-30 1987-12-30 Ferromagnetic antibodies for contrast enhancement of in vivo magnetic resonance imaging

Applications Claiming Priority (1)

Application Number Priority Date Filing Date Title
DE19873744518 DE3744518A1 (en) 1987-12-30 1987-12-30 Ferromagnetic antibodies for contrast enhancement of in vivo magnetic resonance imaging

Publications (1)

Publication Number Publication Date
DE3744518A1 true DE3744518A1 (en) 1989-07-13

Family

ID=6343842

Family Applications (1)

Application Number Title Priority Date Filing Date
DE19873744518 Withdrawn DE3744518A1 (en) 1987-12-30 1987-12-30 Ferromagnetic antibodies for contrast enhancement of in vivo magnetic resonance imaging

Country Status (1)

Country Link
DE (1) DE3744518A1 (en)

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