Classifications

• • A—HUMAN NECESSITIES
  • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
  • A61B—DIAGNOSIS; SURGERY; IDENTIFICATION
  • A61B5/00—Measuring for diagnostic purposes; Identification of persons
  • A61B5/05—Detecting, measuring or recording for diagnosis by means of electric currents or magnetic fields; Measuring using microwaves or radio waves
  • A61B5/055—Detecting, measuring or recording for diagnosis by means of electric currents or magnetic fields; Measuring using microwaves or radio waves involving electronic [EMR] or nuclear [NMR] magnetic resonance, e.g. magnetic resonance imaging
• • A—HUMAN NECESSITIES
  • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
  • A61B—DIAGNOSIS; SURGERY; IDENTIFICATION
  • A61B5/00—Measuring for diagnostic purposes; Identification of persons
  • A61B5/48—Other medical applications
  • A61B5/4836—Diagnosis combined with treatment in closed-loop systems or methods
  • A61B5/4839—Diagnosis combined with treatment in closed-loop systems or methods combined with drug delivery
• • A—HUMAN NECESSITIES
  • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
  • A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
  • A61K41/00—Medicinal preparations obtained by treating materials with wave energy or particle radiation ; Therapies using these preparations
  • A61K41/0057—Photodynamic therapy with a photosensitizer, i.e. agent able to produce reactive oxygen species upon exposure to light or radiation, e.g. UV or visible light; photocleavage of nucleic acids with an agent
  • A61K41/0061—5-aminolevulinic acid-based PDT: 5-ALA-PDT involving porphyrins or precursors of protoporphyrins generated in vivo from 5-ALA
• • A—HUMAN NECESSITIES
  • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
  • A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
  • A61K41/00—Medicinal preparations obtained by treating materials with wave energy or particle radiation ; Therapies using these preparations
  • A61K41/0057—Photodynamic therapy with a photosensitizer, i.e. agent able to produce reactive oxygen species upon exposure to light or radiation, e.g. UV or visible light; photocleavage of nucleic acids with an agent
  • A61K41/0071—PDT with porphyrins having exactly 20 ring atoms, i.e. based on the non-expanded tetrapyrrolic ring system, e.g. bacteriochlorin, chlorin-e6, or phthalocyanines
• • A—HUMAN NECESSITIES
  • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
  • A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
  • A61K41/00—Medicinal preparations obtained by treating materials with wave energy or particle radiation ; Therapies using these preparations
  • A61K41/0057—Photodynamic therapy with a photosensitizer, i.e. agent able to produce reactive oxygen species upon exposure to light or radiation, e.g. UV or visible light; photocleavage of nucleic acids with an agent
  • A61K41/0076—PDT with expanded (metallo)porphyrins, i.e. having more than 20 ring atoms, e.g. texaphyrins, sapphyrins, hexaphyrins, pentaphyrins, porphocyanines
• • A—HUMAN NECESSITIES
  • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
  • A61N—ELECTROTHERAPY; MAGNETOTHERAPY; RADIATION THERAPY; ULTRASOUND THERAPY
  • A61N5/00—Radiation therapy
  • A61N5/06—Radiation therapy using light
  • A61N5/0613—Apparatus adapted for a specific treatment
  • A61N5/062—Photodynamic therapy, i.e. excitation of an agent
• • G—PHYSICS
  • G01—MEASURING; TESTING
  • G01R—MEASURING ELECTRIC VARIABLES; MEASURING MAGNETIC VARIABLES
  • G01R33/00—Arrangements or instruments for measuring magnetic variables
  • G01R33/20—Arrangements or instruments for measuring magnetic variables involving magnetic resonance
  • G01R33/44—Arrangements or instruments for measuring magnetic variables involving magnetic resonance using nuclear magnetic resonance [NMR]
  • G01R33/48—NMR imaging systems
  • G01R33/4806—Functional imaging of brain activation

Definitions

• the present invention is in the field of clinical monitoring and guidance and relates to a magnetic resonance imaging (MRI) method based on the blood oxygenation level-dependent (BOLD) effect for this purpose, particularly in photodynamic therapy (PDT).
• MRI magnetic resonance imaging
• BOLD blood oxygenation level-dependent
• Instant illumination following intravenous sensitizer administration (with no drug-light time interval (DLTI)) was shown to induce capillary occlusion, hemorrhage and blood stasis, resulting in tumor necrosis and eradication (Zilberstein et al., 2001).
• IPM fluorescent intravital microscopy
• Figs. 4A-4C show photochemical reduction in sP0 2 recorded in human blood using Pd-Bpheid (100 ⁇ g/ml) and light (170 mW/cm 2 ).
• (4A) Spectroscopically: without (solid circles, light alone) or with Pd-Bpheid (open circles, light and Pd- Bpheid). To allow spectroscopic sP0 2 measurements, the light was fractionated 10 x (1 min light, and 40 sec dark) to enable 8 repetitive 5 sec readings each. Gray and white areas represent light and dark time periods, respectively.
• the disease or disorder treatable by local embolization may also be a non- malignant disease such as, but not limited to, psoriasis, rheumatoid arthritis, benign prostate hyperplasia, benign mesothelioma, menorrhagia, actinic keratosis (a precancerous disorder that about 20% of the cases develop into squamous cell carcinoma) or an ophthalmologic disease or disorder, particularly age-related macular degeneration (AMD).
• ALD age-related macular degeneration
• disease or disorder treatable by local recanalization means a treatment leading to photodynamic reopening of previously occluded blood vessels.
• cardiovascular disorders such as, but not limited to, restenosis after angioplasty or atherosclerosis.
• the sensitizer used in the present invention is the sensitizer used in the present invention.
• sensitizer is the supramolecular assembly consisting of a water-dispersed polystyrene latex with an embedded scintillating compound, 2,5-diphenyloxazole, and an externally attached hematoporphyrin described by Kokotov et al., 1994.
• the term "functional clinical guidance” means the interactive use of the information obtained by the online BOLD-MRI method for accurate delivery of irradiation to the target region of interest, e.g. the diseased region, within the patient's body. Consequently, these data can be used for monitoring and follow-up of treatment progression.
• the changes in the BOLD-MRI contrast relate to the changes between the basal MR signal intensity in images taken prior to treatment and the MR signal intensity in images taken at discrete time points during and/or at the end of the treatment.
• a BOLD weighted anatomical MR- image of the region of interest within the patient's body is generated before administration of the sensitizer to the patient (t 0 ), this baseline image showing tumor location.
• the online BOLD-MRI method can be performed intraoperatively for real-time assessment of tumor response to PDT, for example in course of brain tumor operation.
• the online BOLD-MRI method is performed for functional clinical guidance of PDT for pre-therapeutic imaging of the region of interest prior to the therapeutic treatment.
• the sensitizer is non-cytotoxic or is a cytotoxic agent used in a non-therapeutic sub-destructive dose such as to generate minimally destructive or toxic conditions in the region of interest.
• the experiments were performed inside the magnet during the MRI recording (see details below). Room temperature was kept constant (28°C) throughout the experiments.
• MRI data was analyzed using Matlab (The Math Works Inc., Natick, MA, USA), Orisis (Version 4.0.9, Geneva, Switzerland) and Paravision 2.1.1 (Bruker, Rheinstetten, Germany).
• MR signal intensity was derived from each image, either from the region of interest inside the tumor or in control tissue, and normalized to the first image.
• Response maps were generated by division of each image by the average of the first 2 pre-PDT images.
• R2* maps were derived by noise weighted linear regression of log(SI), for each pixel. Only pixels with fit of R >0.36 were analyzed.
• R2* MRI relaxivity parameter; R : statistical correlation parameter.
• mice Male CD1 nude mice, s.c. implanted with M2R melanoma xenografts were i.v.-injected with Pd-Bpheid (5 mg/kg) and instantly illuminated for 10 minutes (102 J/cm 2 ). Hemorrhagic tumor necrosis (10/11 mice within 24-48 h) was accompanied by a strong inflammatory response. Tumors in untreated (4/4) light (4/4 mice) or dark (4/4 mice) controls continued to grow reaching ⁇ 10% of body volume by 9 ⁇ 3 days. Photographs of one mouse were taken before (day zero) and up to 54 days post-treatment, when the mouse was considered cured. As shown in Fig. 1, severe necrotic lesion can be noted in the tumor area (days 6 and 10), followed by tissue remodeling (days 21 and 40) and cure (day 54).
• Figs. 2D-2F are parallel adjacent sections of 2D, 2E and 2F, respectively, stained with hematoxylin-eosin.
• Water-filtered infrared-A radiation a novel technique for localized hyperthermia in combination with bacteriochlorophyll-based photodynamic therapy. Int J Hyperthermia. 15, 467-474 (1999).

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• Health & Medical Sciences (AREA)
• Life Sciences & Earth Sciences (AREA)
• General Health & Medical Sciences (AREA)
• Chemical & Material Sciences (AREA)
• Veterinary Medicine (AREA)
• Public Health (AREA)
• Physics & Mathematics (AREA)
• Animal Behavior & Ethology (AREA)
• Engineering & Computer Science (AREA)
• Molecular Biology (AREA)
• Biomedical Technology (AREA)
• Medicinal Chemistry (AREA)
• Nuclear Medicine, Radiotherapy & Molecular Imaging (AREA)
• Pharmacology & Pharmacy (AREA)
• Biophysics (AREA)
• Pathology (AREA)
• Biochemistry (AREA)
• Radiology & Medical Imaging (AREA)
• Epidemiology (AREA)
• Surgery (AREA)
• Heart & Thoracic Surgery (AREA)
• Medical Informatics (AREA)
• High Energy & Nuclear Physics (AREA)
• Bioinformatics & Cheminformatics (AREA)
• General Physics & Mathematics (AREA)
• Condensed Matter Physics & Semiconductors (AREA)
• Neurosurgery (AREA)
• Medicines Containing Antibodies Or Antigens For Use As Internal Diagnostic Agents (AREA)
• Magnetic Resonance Imaging Apparatus (AREA)
• Radiation-Therapy Devices (AREA)
• Medicines That Contain Protein Lipid Enzymes And Other Medicines (AREA)
• Acyclic And Carbocyclic Compounds In Medicinal Compositions (AREA)

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• 2003
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  • 2003-05-08 WO PCT/IL2003/000371 patent/WO2003094695A2/en not_active Ceased
  • 2003-05-08 US US10/513,656 patent/US7715901B2/en not_active Expired - Fee Related
  • 2003-05-08 CA CA002485224A patent/CA2485224A1/en not_active Abandoned
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• 2004
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