WO2001026695A1 - Techniques et appareil permettant de caracteriser des lesions dans les vaisseaux sanguins ou d'autres lumieres corporelles - Google Patents
Techniques et appareil permettant de caracteriser des lesions dans les vaisseaux sanguins ou d'autres lumieres corporelles 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
- Authority
- WO
- WIPO (PCT)
- Prior art keywords
- detector
- radiation
- marker
- introducing
- body lumen
- Prior art date
Links
- 238000000034 method Methods 0.000 title claims abstract description 61
- 230000003902 lesion Effects 0.000 title claims abstract description 48
- 210000004204 blood vessel Anatomy 0.000 title claims description 18
- 239000003550 marker Substances 0.000 claims abstract description 46
- 230000002285 radioactive effect Effects 0.000 claims abstract description 7
- 230000005855 radiation Effects 0.000 claims description 62
- 238000001514 detection method Methods 0.000 claims description 44
- 239000000126 substance Substances 0.000 claims description 28
- 210000005166 vasculature Anatomy 0.000 claims description 13
- 230000027455 binding Effects 0.000 claims description 11
- 239000000463 material Substances 0.000 claims description 8
- 230000009885 systemic effect Effects 0.000 claims description 5
- 238000002347 injection Methods 0.000 claims description 4
- 239000007924 injection Substances 0.000 claims description 4
- 230000002792 vascular Effects 0.000 claims description 4
- 238000009825 accumulation Methods 0.000 claims description 3
- 239000003153 chemical reaction reagent Substances 0.000 claims description 2
- 238000010348 incorporation Methods 0.000 claims 2
- 231100000216 vascular lesion Toxicity 0.000 claims 1
- 238000011065 in-situ storage Methods 0.000 abstract description 9
- 201000010099 disease Diseases 0.000 abstract description 7
- 208000037265 diseases, disorders, signs and symptoms Diseases 0.000 abstract description 7
- 230000003143 atherosclerotic effect Effects 0.000 abstract description 5
- 230000004087 circulation Effects 0.000 abstract description 2
- 238000011282 treatment Methods 0.000 description 9
- 230000017531 blood circulation Effects 0.000 description 5
- 238000006243 chemical reaction Methods 0.000 description 5
- 239000003795 chemical substances by application Substances 0.000 description 4
- 238000003745 diagnosis Methods 0.000 description 4
- 210000002540 macrophage Anatomy 0.000 description 4
- 206010028980 Neoplasm Diseases 0.000 description 3
- 238000013459 approach Methods 0.000 description 3
- 230000001413 cellular effect Effects 0.000 description 3
- 208000029078 coronary artery disease Diseases 0.000 description 3
- 238000011156 evaluation Methods 0.000 description 3
- 238000003384 imaging method Methods 0.000 description 3
- 230000004807 localization Effects 0.000 description 3
- 208000010125 myocardial infarction Diseases 0.000 description 3
- 210000004165 myocardium Anatomy 0.000 description 3
- 230000002062 proliferating effect Effects 0.000 description 3
- 230000035945 sensitivity Effects 0.000 description 3
- 210000002460 smooth muscle Anatomy 0.000 description 3
- YBJHBAHKTGYVGT-ZKWXMUAHSA-N (+)-Biotin Chemical compound N1C(=O)N[C@@H]2[C@H](CCCCC(=O)O)SC[C@@H]21 YBJHBAHKTGYVGT-ZKWXMUAHSA-N 0.000 description 2
- 208000037260 Atherosclerotic Plaque Diseases 0.000 description 2
- 102000007330 LDL Lipoproteins Human genes 0.000 description 2
- 108010007622 LDL Lipoproteins Proteins 0.000 description 2
- 102000004895 Lipoproteins Human genes 0.000 description 2
- 108090001030 Lipoproteins Proteins 0.000 description 2
- 102000005741 Metalloproteases Human genes 0.000 description 2
- 108010006035 Metalloproteases Proteins 0.000 description 2
- 210000004027 cell Anatomy 0.000 description 2
- HVYWMOMLDIMFJA-DPAQBDIFSA-N cholesterol Chemical compound C1C=C2C[C@@H](O)CC[C@]2(C)[C@@H]2[C@@H]1[C@@H]1CC[C@H]([C@H](C)CCCC(C)C)[C@@]1(C)CC2 HVYWMOMLDIMFJA-DPAQBDIFSA-N 0.000 description 2
- 238000002591 computed tomography Methods 0.000 description 2
- 230000007423 decrease Effects 0.000 description 2
- 239000000975 dye Substances 0.000 description 2
- 230000005865 ionizing radiation Effects 0.000 description 2
- 239000003446 ligand Substances 0.000 description 2
- 238000002595 magnetic resonance imaging Methods 0.000 description 2
- 238000012014 optical coherence tomography Methods 0.000 description 2
- 238000004806 packaging method and process Methods 0.000 description 2
- 239000002243 precursor Substances 0.000 description 2
- 102000004169 proteins and genes Human genes 0.000 description 2
- 108090000623 proteins and genes Proteins 0.000 description 2
- 239000000758 substrate Substances 0.000 description 2
- 210000001519 tissue Anatomy 0.000 description 2
- 210000003932 urinary bladder Anatomy 0.000 description 2
- AOYNUTHNTBLRMT-SLPGGIOYSA-N 2-deoxy-2-fluoro-aldehydo-D-glucose Chemical group OC[C@@H](O)[C@@H](O)[C@H](O)[C@@H](F)C=O AOYNUTHNTBLRMT-SLPGGIOYSA-N 0.000 description 1
- 206010002329 Aneurysm Diseases 0.000 description 1
- 206010002388 Angina unstable Diseases 0.000 description 1
- 206010003210 Arteriosclerosis Diseases 0.000 description 1
- 201000001320 Atherosclerosis Diseases 0.000 description 1
- 108090001008 Avidin Proteins 0.000 description 1
- 206010004446 Benign prostatic hyperplasia Diseases 0.000 description 1
- OBMZMSLWNNWEJA-XNCRXQDQSA-N C1=CC=2C(C[C@@H]3NC(=O)[C@@H](NC(=O)[C@H](NC(=O)N(CC#CCN(CCCC[C@H](NC(=O)[C@@H](CC4=CC=CC=C4)NC3=O)C(=O)N)CC=C)NC(=O)[C@@H](N)C)CC3=CNC4=C3C=CC=C4)C)=CNC=2C=C1 Chemical compound C1=CC=2C(C[C@@H]3NC(=O)[C@@H](NC(=O)[C@H](NC(=O)N(CC#CCN(CCCC[C@H](NC(=O)[C@@H](CC4=CC=CC=C4)NC3=O)C(=O)N)CC=C)NC(=O)[C@@H](N)C)CC3=CNC4=C3C=CC=C4)C)=CNC=2C=C1 OBMZMSLWNNWEJA-XNCRXQDQSA-N 0.000 description 1
- 206010008479 Chest Pain Diseases 0.000 description 1
- 206010053567 Coagulopathies Diseases 0.000 description 1
- 206010009944 Colon cancer Diseases 0.000 description 1
- 206010011091 Coronary artery thrombosis Diseases 0.000 description 1
- 208000000461 Esophageal Neoplasms Diseases 0.000 description 1
- 206010061218 Inflammation Diseases 0.000 description 1
- 102000004856 Lectins Human genes 0.000 description 1
- 108090001090 Lectins Proteins 0.000 description 1
- 206010058467 Lung neoplasm malignant Diseases 0.000 description 1
- 102000014962 Monocyte Chemoattractant Proteins Human genes 0.000 description 1
- 108010064136 Monocyte Chemoattractant Proteins Proteins 0.000 description 1
- 206010030155 Oesophageal carcinoma Diseases 0.000 description 1
- 101710176384 Peptide 1 Proteins 0.000 description 1
- 108010053210 Phycocyanin Proteins 0.000 description 1
- 206010060862 Prostate cancer Diseases 0.000 description 1
- 208000000236 Prostatic Neoplasms Diseases 0.000 description 1
- 102000002262 Thromboplastin Human genes 0.000 description 1
- 108010000499 Thromboplastin Proteins 0.000 description 1
- 208000007536 Thrombosis Diseases 0.000 description 1
- 208000007814 Unstable Angina Diseases 0.000 description 1
- KRHYYFGTRYWZRS-BJUDXGSMSA-N ac1l2y5h Chemical compound [18FH] KRHYYFGTRYWZRS-BJUDXGSMSA-N 0.000 description 1
- 239000002253 acid Substances 0.000 description 1
- 150000007513 acids Chemical class 0.000 description 1
- 230000003213 activating effect Effects 0.000 description 1
- 206010000891 acute myocardial infarction Diseases 0.000 description 1
- 238000002583 angiography Methods 0.000 description 1
- 238000002399 angioplasty Methods 0.000 description 1
- 239000000427 antigen Substances 0.000 description 1
- 102000036639 antigens Human genes 0.000 description 1
- 108091007433 antigens Proteins 0.000 description 1
- 208000011775 arteriosclerosis disease Diseases 0.000 description 1
- 210000001367 artery Anatomy 0.000 description 1
- 125000005228 aryl sulfonate group Chemical group 0.000 description 1
- 238000000376 autoradiography Methods 0.000 description 1
- 230000015572 biosynthetic process Effects 0.000 description 1
- 229960002685 biotin Drugs 0.000 description 1
- 235000020958 biotin Nutrition 0.000 description 1
- 239000011616 biotin Substances 0.000 description 1
- 201000011510 cancer Diseases 0.000 description 1
- 230000004663 cell proliferation Effects 0.000 description 1
- 230000002490 cerebral effect Effects 0.000 description 1
- 210000003679 cervix uteri Anatomy 0.000 description 1
- 238000012512 characterization method Methods 0.000 description 1
- 235000012000 cholesterol Nutrition 0.000 description 1
- 230000035602 clotting Effects 0.000 description 1
- 208000029742 colonic neoplasm Diseases 0.000 description 1
- 150000001875 compounds Chemical class 0.000 description 1
- 239000012141 concentrate Substances 0.000 description 1
- 239000000470 constituent Substances 0.000 description 1
- 238000007796 conventional method Methods 0.000 description 1
- 208000002528 coronary thrombosis Diseases 0.000 description 1
- 210000004351 coronary vessel Anatomy 0.000 description 1
- 230000006378 damage Effects 0.000 description 1
- 238000011161 development Methods 0.000 description 1
- 230000000694 effects Effects 0.000 description 1
- 210000002889 endothelial cell Anatomy 0.000 description 1
- 230000003511 endothelial effect Effects 0.000 description 1
- 238000005516 engineering process Methods 0.000 description 1
- 210000003743 erythrocyte Anatomy 0.000 description 1
- 201000004101 esophageal cancer Diseases 0.000 description 1
- 210000003238 esophagus Anatomy 0.000 description 1
- 230000005284 excitation Effects 0.000 description 1
- GNBHRKFJIUUOQI-UHFFFAOYSA-N fluorescein Chemical compound O1C(=O)C2=CC=CC=C2C21C1=CC=C(O)C=C1OC1=CC(O)=CC=C21 GNBHRKFJIUUOQI-UHFFFAOYSA-N 0.000 description 1
- 230000001939 inductive effect Effects 0.000 description 1
- 230000008595 infiltration Effects 0.000 description 1
- 238000001764 infiltration Methods 0.000 description 1
- 210000004969 inflammatory cell Anatomy 0.000 description 1
- 230000004054 inflammatory process Effects 0.000 description 1
- 238000001802 infusion Methods 0.000 description 1
- 201000004332 intermediate coronary syndrome Diseases 0.000 description 1
- 238000002372 labelling Methods 0.000 description 1
- 238000001307 laser spectroscopy Methods 0.000 description 1
- 239000002523 lectin Substances 0.000 description 1
- 238000004020 luminiscence type Methods 0.000 description 1
- 201000005202 lung cancer Diseases 0.000 description 1
- 208000020816 lung neoplasm Diseases 0.000 description 1
- 210000004698 lymphocyte Anatomy 0.000 description 1
- 230000005291 magnetic effect Effects 0.000 description 1
- 238000013507 mapping Methods 0.000 description 1
- 230000002503 metabolic effect Effects 0.000 description 1
- 230000004060 metabolic process Effects 0.000 description 1
- 239000000203 mixture Substances 0.000 description 1
- 238000012986 modification Methods 0.000 description 1
- 230000004048 modification Effects 0.000 description 1
- 210000001616 monocyte Anatomy 0.000 description 1
- 239000005445 natural material Substances 0.000 description 1
- 108020004707 nucleic acids Proteins 0.000 description 1
- 102000039446 nucleic acids Human genes 0.000 description 1
- 150000007523 nucleic acids Chemical class 0.000 description 1
- 239000002777 nucleoside Substances 0.000 description 1
- 125000003835 nucleoside group Chemical group 0.000 description 1
- 239000002773 nucleotide Substances 0.000 description 1
- 125000003729 nucleotide group Chemical group 0.000 description 1
- 230000003287 optical effect Effects 0.000 description 1
- 210000000056 organ Anatomy 0.000 description 1
- 230000005298 paramagnetic effect Effects 0.000 description 1
- 239000002245 particle Substances 0.000 description 1
- 230000000149 penetrating effect Effects 0.000 description 1
- 230000002093 peripheral effect Effects 0.000 description 1
- 238000004393 prognosis Methods 0.000 description 1
- 230000035755 proliferation Effects 0.000 description 1
- 230000002035 prolonged effect Effects 0.000 description 1
- 239000000700 radioactive tracer Substances 0.000 description 1
- 239000012217 radiopharmaceutical Substances 0.000 description 1
- 229940121896 radiopharmaceutical Drugs 0.000 description 1
- 230000002799 radiopharmaceutical effect Effects 0.000 description 1
- 238000012552 review Methods 0.000 description 1
- 239000000523 sample Substances 0.000 description 1
- 230000007651 self-proliferation Effects 0.000 description 1
- 238000011896 sensitive detection Methods 0.000 description 1
- 210000000329 smooth muscle myocyte Anatomy 0.000 description 1
- 239000007787 solid Substances 0.000 description 1
- 230000009870 specific binding Effects 0.000 description 1
- 239000013077 target material Substances 0.000 description 1
- 239000013076 target substance Substances 0.000 description 1
- MPLHNVLQVRSVEE-UHFFFAOYSA-N texas red Chemical compound [O-]S(=O)(=O)C1=CC(S(Cl)(=O)=O)=CC=C1C(C1=CC=2CCCN3CCCC(C=23)=C1O1)=C2C1=C(CCC1)C3=[N+]1CCCC3=C2 MPLHNVLQVRSVEE-UHFFFAOYSA-N 0.000 description 1
- ANRHNWWPFJCPAZ-UHFFFAOYSA-M thionine Chemical compound [Cl-].C1=CC(N)=CC2=[S+]C3=CC(N)=CC=C3N=C21 ANRHNWWPFJCPAZ-UHFFFAOYSA-M 0.000 description 1
- 230000002885 thrombogenetic effect Effects 0.000 description 1
- 238000011277 treatment modality Methods 0.000 description 1
- 238000002604 ultrasonography Methods 0.000 description 1
- 210000000626 ureter Anatomy 0.000 description 1
- 210000003708 urethra Anatomy 0.000 description 1
- 210000004291 uterus Anatomy 0.000 description 1
Classifications
-
- 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 for evaluating the cardiovascular system, e.g. pulse, heart rate, blood pressure or blood flow
- 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 or devices for radiation diagnosis; Apparatus or devices for radiation diagnosis combined with radiation therapy equipment
- A61B6/42—Arrangements for detecting radiation specially adapted for radiation diagnosis
- A61B6/4208—Arrangements for detecting radiation specially adapted for radiation diagnosis characterised by using a particular type of detector
- A61B6/4258—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 or devices for radiation diagnosis; Apparatus or devices for radiation diagnosis combined with radiation therapy equipment
- A61B6/50—Apparatus or devices for radiation diagnosis; Apparatus or devices for radiation diagnosis combined with radiation therapy equipment specially adapted for specific body parts; specially adapted for specific clinical applications
- A61B6/504—Apparatus or devices for radiation diagnosis; Apparatus or devices for radiation diagnosis combined with radiation therapy equipment specially adapted for specific body parts; specially adapted for specific clinical applications for 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.
Landscapes
- Health & Medical Sciences (AREA)
- Life Sciences & Earth Sciences (AREA)
- Engineering & Computer Science (AREA)
- Animal Behavior & Ethology (AREA)
- Veterinary Medicine (AREA)
- Public Health (AREA)
- Medical Informatics (AREA)
- General Health & Medical Sciences (AREA)
- Physics & Mathematics (AREA)
- Optics & Photonics (AREA)
- Molecular Biology (AREA)
- Biophysics (AREA)
- Biomedical Technology (AREA)
- Heart & Thoracic Surgery (AREA)
- Surgery (AREA)
- Pathology (AREA)
- Proteomics, Peptides & Aminoacids (AREA)
- Chemical & Material Sciences (AREA)
- Nuclear Medicine, Radiotherapy & Molecular Imaging (AREA)
- Radiology & Medical Imaging (AREA)
- Epidemiology (AREA)
- Pharmacology & Pharmacy (AREA)
- High Energy & Nuclear Physics (AREA)
- Medicinal Chemistry (AREA)
- Biotechnology (AREA)
- Vascular Medicine (AREA)
- Biochemistry (AREA)
- Oral & Maxillofacial Surgery (AREA)
- Dentistry (AREA)
- Hematology (AREA)
- Cardiology (AREA)
- Physiology (AREA)
- Immunology (AREA)
- Medicines Containing Antibodies Or Antigens For Use As Internal Diagnostic Agents (AREA)
Abstract
Priority Applications (3)
Application Number | Priority Date | Filing Date | Title |
---|---|---|---|
EP00968477A EP1220691A4 (fr) | 1999-10-08 | 2000-09-27 | Techniques et appareil permettant de caracteriser des lesions dans les vaisseaux sanguins ou d'autres lumieres corporelles |
JP2001529756A JP2003511424A (ja) | 1999-10-08 | 2000-09-27 | 血管内およびその他体内管腔内病変部の特性を決定する方法および器具 |
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 |
---|---|
WO2001026695A1 true WO2001026695A1 (fr) | 2001-04-19 |
Family
ID=22570648
Family Applications (1)
Application Number | Title | Priority Date | Filing Date |
---|---|---|---|
PCT/US2000/026751 WO2001026695A1 (fr) | 1999-10-08 | 2000-09-27 | Techniques et appareil permettant de caracteriser des lesions dans les vaisseaux sanguins ou d'autres lumieres corporelles |
Country Status (4)
Country | Link |
---|---|
EP (1) | EP1220691A4 (fr) |
JP (1) | JP2003511424A (fr) |
AU (1) | AU7838000A (fr) |
WO (1) | WO2001026695A1 (fr) |
Families Citing this family (1)
Publication number | Priority date | Publication date | Assignee | Title |
---|---|---|---|---|
ES2390314T3 (es) * | 2006-02-24 | 2012-11-08 | Medibeacon Development, Llc | Agentes ópticos para uso en cirugía |
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/fr not_active Withdrawn
- 2000-09-27 JP JP2001529756A patent/JP2003511424A/ja not_active Withdrawn
- 2000-09-27 WO PCT/US2000/026751 patent/WO2001026695A1/fr not_active Application Discontinuation
- 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 |
---|---|
EP1220691A1 (fr) | 2002-07-10 |
JP2003511424A (ja) | 2003-03-25 |
EP1220691A4 (fr) | 2003-07-16 |
AU7838000A (en) | 2001-04-23 |
Similar Documents
Publication | Publication Date | Title |
---|---|---|
US6782289B1 (en) | Methods and apparatus for characterizing lesions in blood vessels and other body lumens | |
US20030152513A1 (en) | Intravascular delivery of therapeutic and imaging agents to stressed and apoptotic cells using annexin V as a targeting vector | |
Delbeke et al. | Pancreatic tumors: role of imaging in the diagnosis, staging, and treatment | |
Tarkin et al. | PET imaging of inflammation in atherosclerosis | |
Jaffer et al. | Molecular and cellular imaging of atherosclerosis: emerging applications | |
US20020115931A1 (en) | Localizing intravascular lesions on anatomic images | |
Gulec et al. | PET-Probe: evaluation of technical performance and clinical utility of a handheld high-energy gamma probe in oncologic surgery | |
Arulampalam et al. | Positron emission tomography and colorectal cancer | |
US6580016B2 (en) | Animal model for detection of vulnerable plaques | |
Roivainen et al. | Gallium-labelled peptides for imaging of inflammation | |
Martin et al. | Intraoperative radioimmunodetection of colorectal tumor with a hand-held radiation detector | |
Goins et al. | The use of scintigraphic imaging as a tool in the development of liposome formulations | |
Bucerius et al. | Target identification for the diagnosis and intervention of vulnerable atherosclerotic plaques beyond 18 F-fluorodeoxyglucose positron emission tomography imaging: promising tracers on the horizon | |
Chaudhry et al. | Molecular imaging of apoptosis in atherosclerosis by targeting cell membrane phospholipid asymmetry | |
Nakahara et al. | Molecular imaging of vulnerable plaque | |
US20030036699A1 (en) | Methods and systems which use annexin for bioprofiling body lumen | |
Wolters et al. | Cardiovascular molecular imaging of apoptosis | |
Flamen et al. | Position of positron emission tomography and other imaging diagnostic modalities in esophageal cancer | |
WO2007038641A2 (fr) | Procedes et therapies pour le traitement de conditions inflammatoires a l'aide de collagene expose | |
Flamen | Positron emission tomography in colorectal cancer | |
Deane et al. | Targeted imaging of colonic tumors in smad3−/− mice discriminates cancer and inflammation | |
Bengel | Atherosclerosis imaging on the molecular level | |
EP1220691A1 (fr) | Techniques et appareil permettant de caracteriser des lesions dans les vaisseaux sanguins ou d'autres lumieres corporelles | |
Kiess et al. | Translational molecular imaging of prostate cancer | |
Elkhawad et al. | Radiotracer imaging of atherosclerotic plaque biology |
Legal Events
Date | Code | Title | Description |
---|---|---|---|
AK | Designated states |
Kind code of ref document: A1 Designated state(s): AE AG AL AM AT AU AZ BA BB BG BR BY BZ CA CH CN CR CU CZ DE DK DM DZ EE ES FI GB GD GE GH GM HR HU ID IL IN IS JP KE KG KP KR KZ LC LK LR LS LT LU LV MA MD MG MK MN MW MX MZ NO NZ PL PT RO RU SD SE SG SI SK SL TJ TM TR TT TZ UA UG UZ VN YU ZA ZW |
|
AL | Designated countries for regional patents |
Kind code of ref document: A1 Designated state(s): GH GM KE LS MW MZ SD SL SZ TZ UG ZW AM AZ BY KG KZ MD RU TJ TM AT BE CH CY DE DK ES FI FR GB GR IE IT LU MC NL PT SE BF BJ CF CG CI CM GA GN GW ML MR NE SN TD TG |
|
121 | Ep: the epo has been informed by wipo that ep was designated in this application | ||
DFPE | Request for preliminary examination filed prior to expiration of 19th month from priority date (pct application filed before 20040101) | ||
ENP | Entry into the national phase |
Ref country code: JP Ref document number: 2001 529756 Kind code of ref document: A Format of ref document f/p: F |
|
WWE | Wipo information: entry into national phase |
Ref document number: 2000968477 Country of ref document: EP |
|
WWP | Wipo information: published in national office |
Ref document number: 2000968477 Country of ref document: EP |
|
WWW | Wipo information: withdrawn in national office |
Ref document number: 2000968477 Country of ref document: EP |