WO2001026695A1 - Methods and apparatus for characterizing lesions in blood vessels and other body lumens - Google Patents
Methods and apparatus for characterizing lesions in blood vessels and other body lumens Download PDFInfo
- Publication number
- WO2001026695A1 WO2001026695A1 PCT/US2000/026751 US0026751W WO0126695A1 WO 2001026695 A1 WO2001026695 A1 WO 2001026695A1 US 0026751 W US0026751 W US 0026751W WO 0126695 A1 WO0126695 A1 WO 0126695A1
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- WO
- WIPO (PCT)
- Prior art keywords
- detector
- radiation
- marker
- introducing
- body lumen
- Prior art date
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Classifications
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- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
- A61K51/00—Preparations containing radioactive substances for use in therapy or testing in vivo
- A61K51/02—Preparations containing radioactive substances for use in therapy or testing in vivo characterised by the carrier, i.e. characterised by the agent or material covalently linked or complexing the radioactive nucleus
- A61K51/04—Organic compounds
- A61K51/0491—Sugars, nucleosides, nucleotides, oligonucleotides, nucleic acids, e.g. DNA, RNA, nucleic acid aptamers
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61B—DIAGNOSIS; SURGERY; IDENTIFICATION
- A61B5/00—Measuring for diagnostic purposes; Identification of persons
- A61B5/02—Detecting, measuring or recording pulse, heart rate, blood pressure or blood flow; Combined pulse/heart-rate/blood pressure determination; Evaluating a cardiovascular condition not otherwise provided for, e.g. using combinations of techniques provided for in this group with electrocardiography or electroauscultation; Heart catheters for measuring blood pressure
- A61B5/026—Measuring blood flow
- A61B5/0275—Measuring blood flow using tracers, e.g. dye dilution
- A61B5/02755—Radioactive tracers
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61B—DIAGNOSIS; SURGERY; IDENTIFICATION
- A61B6/00—Apparatus for radiation diagnosis, e.g. combined with radiation therapy equipment
- A61B6/42—Apparatus for radiation diagnosis, e.g. combined with radiation therapy equipment with arrangements for detecting radiation specially adapted for radiation diagnosis
- A61B6/4208—Apparatus for radiation diagnosis, e.g. combined with radiation therapy equipment with arrangements for detecting radiation specially adapted for radiation diagnosis characterised by using a particular type of detector
- A61B6/4258—Apparatus for radiation diagnosis, e.g. combined with radiation therapy equipment with arrangements for detecting radiation specially adapted for radiation diagnosis characterised by using a particular type of detector for detecting non x-ray radiation, e.g. gamma radiation
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61B—DIAGNOSIS; SURGERY; IDENTIFICATION
- A61B6/00—Apparatus for radiation diagnosis, e.g. combined with radiation therapy equipment
- A61B6/50—Clinical applications
- A61B6/504—Clinical applications involving diagnosis of blood vessels, e.g. by angiography
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
- A61K51/00—Preparations containing radioactive substances for use in therapy or testing in vivo
- A61K51/02—Preparations containing radioactive substances for use in therapy or testing in vivo characterised by the carrier, i.e. characterised by the agent or material covalently linked or complexing the radioactive nucleus
- A61K51/04—Organic compounds
- A61K51/08—Peptides, e.g. proteins, carriers being peptides, polyamino acids, proteins
- A61K51/10—Antibodies or immunoglobulins; Fragments thereof, the carrier being an antibody, an immunoglobulin or a fragment thereof, e.g. a camelised human single domain antibody or the Fc fragment of an antibody
- A61K51/1018—Antibodies or immunoglobulins; Fragments thereof, the carrier being an antibody, an immunoglobulin or a fragment thereof, e.g. a camelised human single domain antibody or the Fc fragment of an antibody against material from animals or humans
Definitions
- the present invention relates generally to medical devices and methods More particularly, the present invention relates to devices and methods for the u traluminal characterization of lesions in blood vessels and other body lumens
- Coronary artery disease resulting from the build-up of atherosclerotic plaque m the coronary artenes is a leading cause of death in the United States and worldwide
- the plaque buildup causes a narrowing of the artery, commonly referred to as a lesion, which reduces blood flow to the myocardium (heart muscle Ussue) Myocardial infarction (better known as a heart attack) can occur when an arterial lesion abruptly closes the vessel, causing complete cessation of blood flow to portions of the myocardium Even if abrupt closure does not occur, blood flow may decrease resulting in chronically insufficient blood flow which can cause significant Ussue damage over
- vanety of treatment techniques which are available, the cardiologist is faced with a challenge of selecting the particular treatment which is best suited for an individual patient While numerous of diagnostic aids have been developed, no one technique provides all the information which is needed to select a treatment Angiography is very effective in locating lesions in the coronary vasculature, but provides little information concerning the nature of the lesion
- a vanety of imaging techniques have been developed for providing a more detailed view of the lesion, including mtravascular ultrasound (rVUS), angioscopy, laser spectroscopy, computed tomography (CT), magnetic resonance imaging (MRI), and the like None of these techniques, however, is completely successful m determining the exact nature of the lesion In particular, such techniques provide little lnformaUon regarding whether the plaque is stable or unstable Plaques which form in the corona ⁇ es and other vessels compnse inflammatory cells, smooth muscles cells, cholesterol, and fatty substances, and these materials are usually
- radiolabeled agents for detecting atherosclerotic lesions is described in the medical literature. See, for example, Elmaleh et al. (1998) Proc. Natl. Acad. Sci. USA 95:691- 695; Vallabhajosula and Fuster (1997) J. Nucl. Med. 38:1788-1796); Demos et al. (1997) J. Pharm. Sci. 86:167-171; Narula et al. (1995) Circulation 92: 474-484; and Lees et al. (1998)
- U.S. Patent No. 4,660,563 describes the injection of radiolabeled lipoproteins into a patient where the lipoproteins are taken up into regions of arteriosclerotic lesions to permit early detection of those lesions using an external scintillation counter.
- U.S. Patent No. 5,811,814 describes and intravascular radiation-detecting catheter. The catheter is used to locate tagged red blood cells that may accumulate, for example, in an aneurysm.
- U. S. Patent No. 4,660,563 describes the injection of radiolabeled lipoproteins into a patient where the lipoproteins are taken up into regions of arteriosclerotic lesions to permit early detection of those lesions using an external scintillation counter.
- U.S. Patent No. 5,811,814 describes and intravascular radiation-detecting catheter. The catheter is used to locate tagged red blood cells that may accumulate, for example, in an aneurysm.
- U. S. Patent No. 4,660,563 describes the injection of radiolabeled
- No. 5,429,133 describes a laparoscopic probe for detecting radiation concentrated in solid tissue tumors.
- Miniature and flexible radiation detectors intended for medical use are produced by Intra- Medical LLC, Santa Monica, California (www.intra-medical.com). See also U.S. Patent Nos. 4,647,445; 4,877,599; 4,937,067; 5,510,466; 5,711,931; 5,726,153; and WO 89/10760.
- Methods, systems, and kits are provided for assessing characteristics of lesions and other target sites within body lumens, particularly atherosclerotic lesions within a patient's vasculature, including the coronary vasculature, peripheral vasculature, and cerebral vasculature.
- the present invention relies on introducing a labeled marker, typically a radiolabeled marker, to the patient in such a way that the marker localizes within the lesion or target site in some manner which enables or facilitates assessment of that target site.
- Introduction of the labeled marker can be systemic, e.g., by injection or infusion to the patient's blood circulation for evaluation of lesions in the vasculature or other body lumens.
- introduction of the labeled markers can be local, e.g., by catheter delivery directly to a target site within a blood vessel or other body lumen.
- the labeled marker could be introduced systemically and locally in various combinations. After introduction to the patient, the labeled marker is taken up by the lesion or other target site, and the amount of marker (accumulation), rate of uptake, distribution of marker, or other marker characteristics then ddermined in order to facilitate or enable diagnosis or other evaluation of the lesion.
- the amount, rate of uptake, and/or distribution of the marker at or near the lesion or other target site is measured in situ using a detector which has been introduced into the body lumen and positioned in a known or measurable relationship to the lesion or other target site.
- va ⁇ ous conditions related to excessive cellular proliferation can be assessed and monitored
- the presence or prognosis of va ⁇ ous luminal cancers can be determined, such as cancer of the urinary bladder, colon cancer, esophageal cancer, prostate cancer (as well as benign prostate hyperplasia), lung cancer and other bronchial lesions, and the like, can be made
- in situ detection allows the detection of labels, such as visible light, fluorescence, luminescence, and the like, which cannot be detected externally
- tissue- penetrating labels such as radioisotopic radiation
- in situ detection is much more sensitive than external detection This is particularly the case when lower energy (short-path length) radiation sources are used, such as beta ( ⁇ ) radiation, conversion electrons, and the like Detection of lower energy radiation reduces the background which is observed when the tracer concentrates in an adjacent organ or tissue, and is usually not feasible with external detection which, for example, relies on the introduction of gamma ( ⁇ ) radiation-emitting labels and the use of gamma ( ⁇ ) cameras
- the present invention is not limited to the use of beta ( ⁇ ) radiation, conversion electrons, and other short path length radiation, but instead may find use with all types of ionizing radiation under approp ⁇ ate circumstances
- In situ detection also improves detection of both the position and dist ⁇ bution of label immobilized within the body lumen
- the detectors can be configured and/or repositioned so that immobilized radiation and other labels can be determined with an accuracy of less than 5 mm, usually less than 3 mm, preferably less than 2 mm, and often less than 1 mm, along the axis of the body lumen
- a target site such as a region of unstable plaque, a region of proliferating cells, or the like, can greatly facilitate subsequent treatment
- the labeled marker will usually comp ⁇ se at least two components, l e , a detectable label and a binding substance
- the detectable label can be any natural or synthetic mate ⁇ al which is capable of in situ detection using an mtravascular catheter or other intraluminal detector
- radiolabels compnsing radionuclides which emit beta ( ⁇ ) radiation, conversion electrons, and/or gamma ( ⁇ ) radiation
- radiolabels which emit pnma ⁇ ly beta ( ⁇ ) radiation or conversion electrons which have a relatively short path length and permit more precise localization of the target site or mate ⁇ al
- detector(s) capable of quantifying both beta ( ⁇ ) and gamma ( ⁇ ) radiation
- the present invention can employ other visible markers including fluorescent labels, such as fluorescein, Texas Red, phycocyanin dyes, arylsulfonate cyanine dyes, and the like; chemiluminescent labels, and/or bioluminescent labels.
- the present invention can also employ passive labels which respond to inte ⁇ ogation in various ways.
- the labels may comprise paramagnetic or superparamagnetic materials which are detected based on magnetic resonance.
- the labels may be acoustically reflective or absorptive, allowing detection by ultrasonic reflection.
- the labels could be absorptive or reflective to infrared radiation, allowing detection by optical coherence tomography.
- the labels may be activated or fluoresce in the pesence of an appropriate exciting source of energy.
- the labels will typically be bound, covalently or non-covalently, to the binding substance.
- the binding substance can be virtually any material which becomes incorporated into and/or bound to a desired intraluminal target site.
- the material may be a natural substance which becomes incorporated into the lesions, such as low-density lipoproteins or components thereof.
- the binding substances can be a variety of cellular precursors, including proteins, nucleic acids, and the like.
- the binding substances can be prepared or synthesized for specific binding to a target site at the target location.
- antibodies can be prepared to a wide variety of vascular and non-vascular target sites.
- natural receptors and/or ligands will be available for particular target sites.
- monocyte chemoattractant peptide 1 MCP1
- target substance in plaque include lectins whose receptors are upregulated on endothelial cells that overly the plaque.
- Antibodies such as Z2D3 (Khaw et al., Carrio et al., Narula et al.) localize on proliferating smooth muscle in the plaque.
- Another potential agent is fluorodeoxyglucose labeled with fluorine-18. This agent emits positrons and is utilized as an energy substrate by macrophages and monocytes, and it has shown enhanced localization in experimental atherosclerosis models.
- agents include those which bind to tissue factor, lymphocyte surface antigens or secreted compounds, and other secreted proteins that become entrapped within and characteristics of vulnerable plaque.
- the label and binding substance may be bound to each other in any conventional manner Most commonly, moieties on the label and or the binding substance will be de ⁇ vitized to permit covalent attachment Covalent attachment will usually be direct, but in some cases may employ a linking member
- Non-covalent attachment can employ a vanety of non-covalent linkers, such as biotin, avidin, intermediate antibodies, receptors, ligands, and the like
- a vanety of suitable binding techniques are desc ⁇ bed m a review article in Nature Biotechnology (1999) Vol 17, pages 849 and 850, the full disclosure of which is incorporated by reference
- An important aspect of the present invention is the ability to detect and/or image the label in situ after the label has localized in the blood vessel wall or other body lumen Because the label binds to specific target mate ⁇ als within the body lumen, the pattern in which the label has localized will conespond to the pattern of the target matenal in the body lumen Such separate detection may be performed simultaneously, sequentially, or in some combination thereof For example, if the labeled marker comp ⁇ ses low-density lipoproteins, or a component thereof, the labeled marker will bind to atherosclerotic plaque which is actively growing or accumulating and therefore at nsk of being unstable The pattern of label will thus conespond to the pattern of unstable plaque within the patient's vasculature
- Detection of the label and its pattern within the body lumen will be performed using an intraluminal detector, usually a detector capable of detecting ionizing radiation from a radioisotopic label within a particular distance of the label, as discussed in more detail below
- the detector and catheter can be introduced into the body lumen by a variety of conventional techniques
- the prefened techniques will be percutaneous, e g , using a needle and sheath for introduction of a guidewire in a Seldinger access technique
- surgical cutdowns can be used for accessing blood vessels, and a variety of other surgical and minimally invasive techmques can be used for introducing intraluminal detectors into other body lumens
- the nature of the label and charactenstics of the detector will be selected so that an emitted signal from the label will be visible or detectable only within a particular distance of a detecting surface or element of the detector, usually within 5 mm, preferably within 3 mm, and sometimes within 1 mm That is, the detector will only have
- detection of the label will be performed over a minimum length of the body lumen m order to characterize va ⁇ ations m the luminal lesion over that length with the ability to distinguish lesions present at intervals of 3 mm
- the present invention will usually be used to image over a vascular length of at least 30 mm, preferably at least 40 mm, and more preferably at least 50 mm
- Such detection may be achieved by scanning a detector over the length within the blood vessel or other body lumen
- the detector can remain stationary within the lumen and have spatial resolution over the prefened minimum length set forth above without movement of the detector itself
- the detectors will preferably be isotropic over at least their circumference or penphery Regardless of whether the detector is scanned or held stationary du ⁇ ng detection, it will normally be preferred that detection of label over the entire circumference or penphery of the body lumen be performed In other cases, however, it might be desired to perform a directional scan l e , one where a particular radial sector of the body lumen wall is observed
- plaques at different phases of development have varying degrees of smooth muscle proliferation (detectable with Z2D3 antibody localization), varying degrees of macrophage infiltration (detectable with MCP1), varying levels of macrophage metabolism (detectable with the metabolic substrate FDG), and varying degrees of metalloproteinase activity (detectable with labeled antibodies specific for the metalloproteinase)
- smooth muscle proliferation detectable with Z2D3 antibody localization
- MCP1 macrophage infiltration
- MCP1 varying levels of macrophage metabolism
- FDG varying degrees of metalloproteinase activity
- Two or more parameters could be evaluated simultaneously if the radiopharmaceuticals carry radiolabels with substantially different energies or if one radionuchde has a substantially shorter half life than the other(s)
- labels having different natures e g , light emission, fluorescence emission, and/or radioisotopic radiation could be employed and detected simultaneous with minimum interference
- the present invention will permit determination of the axial and circumferential distnbution of the target matenal within the body lumen In the case of atherosclerotic lesions in a blood vessel, this information is particularly suitable for assessing the need for treatment as well as planning particular treatment modalities In particular, the present invention would allow the identification of relatively small lesions, e g , with luminal blockage below 50%, which nonetheless are unstable and require immediate intervention Conversely, larger lesions (above 50% occlusion) which are stable and less in need of immediate intervention can also be identified
- While the present invention is directed at intraluminal detection of marker(s), it may find use in combination with external detection of the same or other markers and/or external detection and imaging of the catheter which is being used for the intraluminal detection
- External detection of immobilized markers may be useful for pre-positionmg of the intraluminal detection catheter and/or for companng information from different markers and targets (where the different markers may be bound to different binding substances having different specificities)
- External detection of the catheter will allow mapping of the vasculature or other luminal system.
- the position of the catheter can be detected fluoroscopically, by MRI, or otherwise, and the position of the internally detected lesions be noted on the external image or map which is created
- the present invention further provides radiation detection devices compnsing an elongate body, typically a catheter, and a radiation detector disposed on the elongate body
- the catheter or other elongate body is configured to access the ntenor of a target body lumen, such as a blood vessel, a ureter, a urethra, an esophagus, a cervix, a uterus, a bladder, or the like
- the radiation detector is capable of sensing radiation emitted into the body lumen and which is incident along the elongate body
- the radiation detector will be capable of sensing radiation over a length of at least 3 cm, preferably at least 4 cm, and more preferably at least 5 cm
- the radiation detector will be capable of sensing radiation isotropically preferably being equally sensitive in all radial directions over the circumference of the elongate body
- kits for identifying or assessing luminal lesions or other target sites will comprise a radiation detector configured to be introduced into a body lumen and instructions for use according to any of the methods described above.
- kits according to the present invention may comprise a radiation detector configured to be introduced into a body lumen, a container for holding a reagent comprising a substance capable of binding to a target material within the body lumen and a detectable label bound to the substance, and a package for holding the radiation detector and the container together.
- the container may be any conventional container, such as a box, tray, tube, pouch, or the like. Instructions for use will typically be provided on a separate package insert, but in some cases may be printed in whole or in part on the packaging itself. Usually, the radiation detector will be maintained sterilely within the packaging.
Abstract
Description
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Priority Applications (3)
Application Number | Priority Date | Filing Date | Title |
---|---|---|---|
JP2001529756A JP2003511424A (en) | 1999-10-08 | 2000-09-27 | Methods and apparatus for characterizing intravascular and other intraluminal lesions |
EP00968477A EP1220691A4 (en) | 1999-10-08 | 2000-09-27 | Methods and apparatus for characterizing lesions in blood vessels and other body lumens |
AU78380/00A AU7838000A (en) | 1999-10-08 | 2000-09-27 | Methods and apparatus for characterizing lesions in blood vessels and other body lumens |
Applications Claiming Priority (2)
Application Number | Priority Date | Filing Date | Title |
---|---|---|---|
US15900199P | 1999-10-08 | 1999-10-08 | |
US60/159,001 | 1999-10-08 |
Publications (1)
Publication Number | Publication Date |
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WO2001026695A1 true WO2001026695A1 (en) | 2001-04-19 |
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Family Applications (1)
Application Number | Title | Priority Date | Filing Date |
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PCT/US2000/026751 WO2001026695A1 (en) | 1999-10-08 | 2000-09-27 | Methods and apparatus for characterizing lesions in blood vessels and other body lumens |
Country Status (4)
Country | Link |
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EP (1) | EP1220691A4 (en) |
JP (1) | JP2003511424A (en) |
AU (1) | AU7838000A (en) |
WO (1) | WO2001026695A1 (en) |
Families Citing this family (1)
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US9283288B2 (en) * | 2006-02-24 | 2016-03-15 | Medibeacon, Inc. | Methods of using optical agents |
Citations (1)
Publication number | Priority date | Publication date | Assignee | Title |
---|---|---|---|---|
US5751781A (en) * | 1995-10-07 | 1998-05-12 | Elekta Ab | Apparatus for treating a patient |
Family Cites Families (4)
Publication number | Priority date | Publication date | Assignee | Title |
---|---|---|---|---|
US3598109A (en) * | 1967-09-11 | 1971-08-10 | Tokyo Shibaura Electric Co | Radiation detector for insertion into a blood vessel |
US3670719A (en) * | 1968-10-25 | 1972-06-20 | Tokyo Shibaura Electric Co | Catheter type semiconductor radiation detector |
US5811814A (en) * | 1996-02-12 | 1998-09-22 | Cordis Corporation | Radiation measuring catheter apparatus and method |
US5932879A (en) * | 1996-05-07 | 1999-08-03 | Regents Of The University Of Michigan | Solid state beta-sensitive surgical probe |
-
2000
- 2000-09-27 EP EP00968477A patent/EP1220691A4/en not_active Withdrawn
- 2000-09-27 WO PCT/US2000/026751 patent/WO2001026695A1/en not_active Application Discontinuation
- 2000-09-27 JP JP2001529756A patent/JP2003511424A/en not_active Withdrawn
- 2000-09-27 AU AU78380/00A patent/AU7838000A/en not_active Abandoned
Patent Citations (1)
Publication number | Priority date | Publication date | Assignee | Title |
---|---|---|---|---|
US5751781A (en) * | 1995-10-07 | 1998-05-12 | Elekta Ab | Apparatus for treating a patient |
Non-Patent Citations (3)
Title |
---|
OHDAIRA T. ET AL.: "Intraoperative localization of colorectal tumors in the early stages using a marking clip detector system", DISEASES OF THE COLON AND RECTUM, vol. 42, no. 10, October 1999 (1999-10-01), pages 1353 - 1355, POSTER PRESENTATION IN MAY 1998, XP002935362 * |
PARSONS R.: "Fluoroscopically assisted thromboembolectomy: An improved method for treating acute arterial occlusions", ANNALS OF VASCULAR SURGERY, vol. 10, no. 3, May 1996 (1996-05-01), pages 201 - 210, XP002935363 * |
See also references of EP1220691A4 * |
Also Published As
Publication number | Publication date |
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AU7838000A (en) | 2001-04-23 |
JP2003511424A (en) | 2003-03-25 |
EP1220691A4 (en) | 2003-07-16 |
EP1220691A1 (en) | 2002-07-10 |
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