JP5171970B2 - 分子内発光抑制式近赤外蛍光プローブ - Google Patents
分子内発光抑制式近赤外蛍光プローブ Download PDFInfo
- Publication number
- JP5171970B2 JP5171970B2 JP2011005396A JP2011005396A JP5171970B2 JP 5171970 B2 JP5171970 B2 JP 5171970B2 JP 2011005396 A JP2011005396 A JP 2011005396A JP 2011005396 A JP2011005396 A JP 2011005396A JP 5171970 B2 JP5171970 B2 JP 5171970B2
- Authority
- JP
- Japan
- Prior art keywords
- probe
- fluorescent dye
- fluorescence
- fluorescent
- target tissue
- 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.)
- Expired - Lifetime
Links
- 239000007850 fluorescent dye Substances 0.000 title claims description 114
- 230000001629 suppression Effects 0.000 title claims description 15
- 238000004020 luminiscence type Methods 0.000 title claims description 10
- 239000000523 sample Substances 0.000 claims description 103
- 210000001519 tissue Anatomy 0.000 claims description 46
- 125000006850 spacer group Chemical group 0.000 claims description 32
- 230000004913 activation Effects 0.000 claims description 30
- 238000000034 method Methods 0.000 claims description 27
- 238000012634 optical imaging Methods 0.000 claims description 19
- 108010039918 Polylysine Proteins 0.000 claims description 18
- 238000001727 in vivo Methods 0.000 claims description 18
- 229920000656 polylysine Polymers 0.000 claims description 18
- 102000004190 Enzymes Human genes 0.000 claims description 17
- 108090000790 Enzymes Proteins 0.000 claims description 17
- 230000005284 excitation Effects 0.000 claims description 17
- 108010072866 Prostate-Specific Antigen Proteins 0.000 claims description 16
- 238000003776 cleavage reaction Methods 0.000 claims description 16
- 230000007017 scission Effects 0.000 claims description 16
- 206010028980 Neoplasm Diseases 0.000 claims description 15
- 108090000765 processed proteins & peptides Proteins 0.000 claims description 15
- 239000002202 Polyethylene glycol Substances 0.000 claims description 13
- 229920001223 polyethylene glycol Polymers 0.000 claims description 13
- 229920001184 polypeptide Polymers 0.000 claims description 13
- 102000004196 processed proteins & peptides Human genes 0.000 claims description 13
- 229920000642 polymer Polymers 0.000 claims description 12
- 230000001681 protective effect Effects 0.000 claims description 11
- 230000002255 enzymatic effect Effects 0.000 claims description 10
- 150000004676 glycans Chemical class 0.000 claims description 10
- 238000003384 imaging method Methods 0.000 claims description 10
- 229920001282 polysaccharide Polymers 0.000 claims description 10
- 239000005017 polysaccharide Substances 0.000 claims description 10
- 102000005962 receptors Human genes 0.000 claims description 10
- 108020003175 receptors Proteins 0.000 claims description 10
- 230000003993 interaction Effects 0.000 claims description 7
- RAXXELZNTBOGNW-UHFFFAOYSA-N imidazole Natural products C1=CNC=N1 RAXXELZNTBOGNW-UHFFFAOYSA-N 0.000 claims description 6
- 125000000956 methoxy group Chemical group [H]C([H])([H])O* 0.000 claims description 6
- 102000008394 Immunoglobulin Fragments Human genes 0.000 claims description 5
- 108010021625 Immunoglobulin Fragments Proteins 0.000 claims description 5
- 241001465754 Metazoa Species 0.000 claims description 5
- 108010038807 Oligopeptides Proteins 0.000 claims description 5
- 102000015636 Oligopeptides Human genes 0.000 claims description 5
- 239000012588 trypsin Substances 0.000 claims description 5
- REKYPYSUBKSCAT-UHFFFAOYSA-N 3-hydroxypentanoic acid Chemical compound CCC(O)CC(O)=O REKYPYSUBKSCAT-UHFFFAOYSA-N 0.000 claims description 4
- 102100030351 Membrane-associated phosphatidylinositol transfer protein 3 Human genes 0.000 claims description 4
- 101710104263 Membrane-associated phosphatidylinositol transfer protein 3 Proteins 0.000 claims description 4
- 229920000954 Polyglycolide Polymers 0.000 claims description 4
- 108090000631 Trypsin Proteins 0.000 claims description 4
- 102000004142 Trypsin Human genes 0.000 claims description 4
- FSUOQVGBXADQGH-UHFFFAOYSA-M [9-cyano-6-(diethylamino)xanthen-3-ylidene]-[6-(2,5-dioxopyrrolidin-1-yl)oxy-6-oxohexyl]-ethylazanium;chloride Chemical compound [Cl-].C1=C2OC3=CC(N(CC)CC)=CC=C3C(C#N)=C2C=CC1=[N+](CC)CCCCCC(=O)ON1C(=O)CCC1=O FSUOQVGBXADQGH-UHFFFAOYSA-M 0.000 claims description 4
- 239000002253 acid Substances 0.000 claims description 4
- 201000011510 cancer Diseases 0.000 claims description 4
- 230000000694 effects Effects 0.000 claims description 4
- 239000004633 polyglycolic acid Substances 0.000 claims description 4
- 229920001451 polypropylene glycol Polymers 0.000 claims description 4
- 229920001059 synthetic polymer Chemical class 0.000 claims description 4
- 230000008685 targeting Effects 0.000 claims description 4
- 229920002873 Polyethylenimine Chemical class 0.000 claims description 3
- 238000000799 fluorescence microscopy Methods 0.000 claims description 3
- 229920000962 poly(amidoamine) Chemical class 0.000 claims description 3
- -1 polyvalerolactone Polymers 0.000 claims description 3
- 229920002307 Dextran Polymers 0.000 claims description 2
- 229920002125 Sokalan® Chemical class 0.000 claims description 2
- 229920001577 copolymer Polymers 0.000 claims description 2
- 102000039446 nucleic acids Human genes 0.000 claims description 2
- 108020004707 nucleic acids Proteins 0.000 claims description 2
- 150000007523 nucleic acids Chemical class 0.000 claims description 2
- 229920001542 oligosaccharide Polymers 0.000 claims description 2
- 150000002482 oligosaccharides Chemical class 0.000 claims description 2
- 229920000747 poly(lactic acid) Polymers 0.000 claims description 2
- 229920002463 poly(p-dioxanone) polymer Polymers 0.000 claims description 2
- 229920000070 poly-3-hydroxybutyrate Polymers 0.000 claims description 2
- 239000004584 polyacrylic acid Chemical class 0.000 claims description 2
- 229920001610 polycaprolactone Polymers 0.000 claims description 2
- 239000000622 polydioxanone Substances 0.000 claims description 2
- 239000004626 polylactic acid Substances 0.000 claims description 2
- 150000005846 sugar alcohols Chemical class 0.000 claims description 2
- 230000001678 irradiating effect Effects 0.000 claims 4
- 102000007066 Prostate-Specific Antigen Human genes 0.000 claims 2
- 201000010099 disease Diseases 0.000 claims 2
- 208000037265 diseases, disorders, signs and symptoms Diseases 0.000 claims 2
- 102000005600 Cathepsins Human genes 0.000 claims 1
- 108010084457 Cathepsins Proteins 0.000 claims 1
- 238000001514 detection method Methods 0.000 claims 1
- 238000009472 formulation Methods 0.000 claims 1
- 238000004519 manufacturing process Methods 0.000 claims 1
- 239000000203 mixture Substances 0.000 claims 1
- 102100038358 Prostate-specific antigen Human genes 0.000 description 14
- 210000004027 cell Anatomy 0.000 description 10
- 102000003908 Cathepsin D Human genes 0.000 description 8
- 108090000258 Cathepsin D Proteins 0.000 description 8
- 230000002401 inhibitory effect Effects 0.000 description 8
- 230000003287 optical effect Effects 0.000 description 8
- LYCAIKOWRPUZTN-UHFFFAOYSA-N Ethylene glycol Chemical compound OCCO LYCAIKOWRPUZTN-UHFFFAOYSA-N 0.000 description 6
- 241000699666 Mus <mouse, genus> Species 0.000 description 5
- BFMYDTVEBKDAKJ-UHFFFAOYSA-L disodium;(2',7'-dibromo-3',6'-dioxido-3-oxospiro[2-benzofuran-1,9'-xanthene]-4'-yl)mercury;hydrate Chemical compound O.[Na+].[Na+].O1C(=O)C2=CC=CC=C2C21C1=CC(Br)=C([O-])C([Hg])=C1OC1=C2C=C(Br)C([O-])=C1 BFMYDTVEBKDAKJ-UHFFFAOYSA-L 0.000 description 5
- 230000003834 intracellular effect Effects 0.000 description 5
- 238000012360 testing method Methods 0.000 description 5
- 241000699660 Mus musculus Species 0.000 description 4
- 238000010521 absorption reaction Methods 0.000 description 4
- 230000003213 activating effect Effects 0.000 description 4
- 229920000249 biocompatible polymer Polymers 0.000 description 4
- 238000000338 in vitro Methods 0.000 description 4
- 239000000463 material Substances 0.000 description 4
- 238000005259 measurement Methods 0.000 description 4
- 238000011580 nude mouse model Methods 0.000 description 4
- 208000023958 prostate neoplasm Diseases 0.000 description 4
- 210000002966 serum Anatomy 0.000 description 4
- 210000004881 tumor cell Anatomy 0.000 description 4
- 206010006187 Breast cancer Diseases 0.000 description 3
- 208000026310 Breast neoplasm Diseases 0.000 description 3
- 150000001413 amino acids Chemical group 0.000 description 3
- 230000015572 biosynthetic process Effects 0.000 description 3
- 238000000295 emission spectrum Methods 0.000 description 3
- 238000000695 excitation spectrum Methods 0.000 description 3
- 238000002474 experimental method Methods 0.000 description 3
- 125000000524 functional group Chemical group 0.000 description 3
- WGCNASOHLSPBMP-UHFFFAOYSA-N hydroxyacetaldehyde Natural products OCC=O WGCNASOHLSPBMP-UHFFFAOYSA-N 0.000 description 3
- 125000003588 lysine group Chemical group [H]N([H])C([H])([H])C([H])([H])C([H])([H])C([H])([H])C([H])(N([H])[H])C(*)=O 0.000 description 3
- 230000007246 mechanism Effects 0.000 description 3
- 230000035699 permeability Effects 0.000 description 3
- 230000002829 reductive effect Effects 0.000 description 3
- 239000000126 substance Substances 0.000 description 3
- FWMNVWWHGCHHJJ-SKKKGAJSSA-N 4-amino-1-[(2r)-6-amino-2-[[(2r)-2-[[(2r)-2-[[(2r)-2-amino-3-phenylpropanoyl]amino]-3-phenylpropanoyl]amino]-4-methylpentanoyl]amino]hexanoyl]piperidine-4-carboxylic acid Chemical compound C([C@H](C(=O)N[C@H](CC(C)C)C(=O)N[C@H](CCCCN)C(=O)N1CCC(N)(CC1)C(O)=O)NC(=O)[C@H](N)CC=1C=CC=CC=1)C1=CC=CC=C1 FWMNVWWHGCHHJJ-SKKKGAJSSA-N 0.000 description 2
- IASNWHAGGYTEKX-IUCAKERBSA-N Arg-Arg-Gly Chemical compound NC(N)=NCCC[C@H](N)C(=O)N[C@@H](CCCN=C(N)N)C(=O)NCC(O)=O IASNWHAGGYTEKX-IUCAKERBSA-N 0.000 description 2
- 102100027612 Kallikrein-11 Human genes 0.000 description 2
- XUMBMVFBXHLACL-UHFFFAOYSA-N Melanin Chemical compound O=C1C(=O)C(C2=CNC3=C(C(C(=O)C4=C32)=O)C)=C2C4=CNC2=C1C XUMBMVFBXHLACL-UHFFFAOYSA-N 0.000 description 2
- 241000699670 Mus sp. Species 0.000 description 2
- 102000001708 Protein Isoforms Human genes 0.000 description 2
- 108010029485 Protein Isoforms Proteins 0.000 description 2
- UIIMBOGNXHQVGW-UHFFFAOYSA-M Sodium bicarbonate Chemical compound [Na+].OC([O-])=O UIIMBOGNXHQVGW-UHFFFAOYSA-M 0.000 description 2
- 101710152431 Trypsin-like protease Proteins 0.000 description 2
- 238000009825 accumulation Methods 0.000 description 2
- 125000003277 amino group Chemical group 0.000 description 2
- 239000000427 antigen Substances 0.000 description 2
- 102000036639 antigens Human genes 0.000 description 2
- 108091007433 antigens Proteins 0.000 description 2
- 230000008901 benefit Effects 0.000 description 2
- 210000000481 breast Anatomy 0.000 description 2
- 239000000872 buffer Substances 0.000 description 2
- 238000004113 cell culture Methods 0.000 description 2
- 230000002490 cerebral effect Effects 0.000 description 2
- 239000002872 contrast media Substances 0.000 description 2
- 210000004748 cultured cell Anatomy 0.000 description 2
- 230000001419 dependent effect Effects 0.000 description 2
- 238000013461 design Methods 0.000 description 2
- 238000010586 diagram Methods 0.000 description 2
- 239000000539 dimer Substances 0.000 description 2
- 238000005516 engineering process Methods 0.000 description 2
- 210000003754 fetus Anatomy 0.000 description 2
- 239000000835 fiber Substances 0.000 description 2
- 238000002073 fluorescence micrograph Methods 0.000 description 2
- 229910052736 halogen Inorganic materials 0.000 description 2
- 150000002367 halogens Chemical class 0.000 description 2
- 230000005847 immunogenicity Effects 0.000 description 2
- 230000000670 limiting effect Effects 0.000 description 2
- 239000003550 marker Substances 0.000 description 2
- 230000005012 migration Effects 0.000 description 2
- 238000013508 migration Methods 0.000 description 2
- 239000000178 monomer Substances 0.000 description 2
- 238000003333 near-infrared imaging Methods 0.000 description 2
- 238000006213 oxygenation reaction Methods 0.000 description 2
- 210000000064 prostate epithelial cell Anatomy 0.000 description 2
- 235000018102 proteins Nutrition 0.000 description 2
- 102000004169 proteins and genes Human genes 0.000 description 2
- 108090000623 proteins and genes Proteins 0.000 description 2
- 239000011541 reaction mixture Substances 0.000 description 2
- 238000011084 recovery Methods 0.000 description 2
- 239000000243 solution Substances 0.000 description 2
- 238000001228 spectrum Methods 0.000 description 2
- 239000000758 substrate Substances 0.000 description 2
- 238000003786 synthesis reaction Methods 0.000 description 2
- NHJVRSWLHSJWIN-UHFFFAOYSA-N 2,4,6-trinitrobenzenesulfonic acid Chemical compound OS(=O)(=O)C1=C([N+]([O-])=O)C=C([N+]([O-])=O)C=C1[N+]([O-])=O NHJVRSWLHSJWIN-UHFFFAOYSA-N 0.000 description 1
- 102000009027 Albumins Human genes 0.000 description 1
- 108010088751 Albumins Proteins 0.000 description 1
- OMLWNBVRVJYMBQ-YUMQZZPRSA-N Arg-Arg Chemical compound NC(N)=NCCC[C@H](N)C(=O)N[C@@H](CCCN=C(N)N)C(O)=O OMLWNBVRVJYMBQ-YUMQZZPRSA-N 0.000 description 1
- 201000009030 Carcinoma Diseases 0.000 description 1
- VGGSQFUCUMXWEO-UHFFFAOYSA-N Ethene Chemical compound C=C VGGSQFUCUMXWEO-UHFFFAOYSA-N 0.000 description 1
- 239000005977 Ethylene Substances 0.000 description 1
- 208000001382 Experimental Melanoma Diseases 0.000 description 1
- 102000016359 Fibronectins Human genes 0.000 description 1
- 108010067306 Fibronectins Proteins 0.000 description 1
- 102000001554 Hemoglobins Human genes 0.000 description 1
- 108010054147 Hemoglobins Proteins 0.000 description 1
- VIJMRAIWYWRXSR-CIUDSAMLSA-N His-Ser-Ser Chemical compound OC[C@@H](C(O)=O)NC(=O)[C@H](CO)NC(=O)[C@@H](N)CC1=CN=CN1 VIJMRAIWYWRXSR-CIUDSAMLSA-N 0.000 description 1
- 101000856199 Homo sapiens Chymotrypsin-like protease CTRL-1 Proteins 0.000 description 1
- 150000008575 L-amino acids Chemical class 0.000 description 1
- 101710171912 Lysosomal aspartic protease Proteins 0.000 description 1
- 102000035195 Peptidases Human genes 0.000 description 1
- 108091005804 Peptidases Proteins 0.000 description 1
- 239000004698 Polyethylene Substances 0.000 description 1
- 239000004365 Protease Substances 0.000 description 1
- 229920005654 Sephadex Polymers 0.000 description 1
- 239000012507 Sephadex™ Substances 0.000 description 1
- 238000011481 absorbance measurement Methods 0.000 description 1
- 239000006096 absorbing agent Substances 0.000 description 1
- 238000012382 advanced drug delivery Methods 0.000 description 1
- 230000002776 aggregation Effects 0.000 description 1
- 238000004220 aggregation Methods 0.000 description 1
- 230000033115 angiogenesis Effects 0.000 description 1
- 239000007864 aqueous solution Substances 0.000 description 1
- 108010068380 arginylarginine Proteins 0.000 description 1
- 238000003556 assay Methods 0.000 description 1
- 210000002469 basement membrane Anatomy 0.000 description 1
- 229920002988 biodegradable polymer Polymers 0.000 description 1
- 239000004621 biodegradable polymer Substances 0.000 description 1
- 238000006065 biodegradation reaction Methods 0.000 description 1
- 229920001400 block copolymer Polymers 0.000 description 1
- 210000004369 blood Anatomy 0.000 description 1
- 239000008280 blood Substances 0.000 description 1
- 125000003178 carboxy group Chemical group [H]OC(*)=O 0.000 description 1
- 230000015556 catabolic process Effects 0.000 description 1
- 239000006143 cell culture medium Substances 0.000 description 1
- 230000004700 cellular uptake Effects 0.000 description 1
- 230000008859 change Effects 0.000 description 1
- 239000007795 chemical reaction product Substances 0.000 description 1
- 239000003541 chymotrypsin inhibitor Substances 0.000 description 1
- 230000001268 conjugating effect Effects 0.000 description 1
- 230000002950 deficient Effects 0.000 description 1
- 238000006731 degradation reaction Methods 0.000 description 1
- 238000001212 derivatisation Methods 0.000 description 1
- 238000011161 development Methods 0.000 description 1
- 239000012895 dilution Substances 0.000 description 1
- 238000010790 dilution Methods 0.000 description 1
- 239000000975 dye Substances 0.000 description 1
- 230000007613 environmental effect Effects 0.000 description 1
- 210000000981 epithelium Anatomy 0.000 description 1
- 150000002148 esters Chemical class 0.000 description 1
- 210000003722 extracellular fluid Anatomy 0.000 description 1
- 210000001723 extracellular space Anatomy 0.000 description 1
- 210000002950 fibroblast Anatomy 0.000 description 1
- 230000004907 flux Effects 0.000 description 1
- 230000007062 hydrolysis Effects 0.000 description 1
- 238000006460 hydrolysis reaction Methods 0.000 description 1
- 238000011503 in vivo imaging Methods 0.000 description 1
- 238000002329 infrared spectrum Methods 0.000 description 1
- 230000005764 inhibitory process Effects 0.000 description 1
- 238000001990 intravenous administration Methods 0.000 description 1
- 230000005865 ionizing radiation Effects 0.000 description 1
- 239000010985 leather Substances 0.000 description 1
- 239000003446 ligand Substances 0.000 description 1
- 210000004216 mammary stem cell Anatomy 0.000 description 1
- 238000000386 microscopy Methods 0.000 description 1
- FEMOMIGRRWSMCU-UHFFFAOYSA-N ninhydrin Chemical compound C1=CC=C2C(=O)C(O)(O)C(=O)C2=C1 FEMOMIGRRWSMCU-UHFFFAOYSA-N 0.000 description 1
- 230000008884 pinocytosis Effects 0.000 description 1
- 229920000729 poly(L-lysine) polymer Polymers 0.000 description 1
- 229920001308 poly(aminoacid) Polymers 0.000 description 1
- 229920000573 polyethylene Polymers 0.000 description 1
- 102000040430 polynucleotide Human genes 0.000 description 1
- 108091033319 polynucleotide Proteins 0.000 description 1
- 239000002157 polynucleotide Substances 0.000 description 1
- 238000012805 post-processing Methods 0.000 description 1
- 150000003141 primary amines Chemical class 0.000 description 1
- 238000012545 processing Methods 0.000 description 1
- 210000002307 prostate Anatomy 0.000 description 1
- 125000006239 protecting group Chemical group 0.000 description 1
- 230000002797 proteolythic effect Effects 0.000 description 1
- 238000006862 quantum yield reaction Methods 0.000 description 1
- 230000009257 reactivity Effects 0.000 description 1
- 238000002165 resonance energy transfer Methods 0.000 description 1
- 230000000717 retained effect Effects 0.000 description 1
- 238000012552 review Methods 0.000 description 1
- 210000000582 semen Anatomy 0.000 description 1
- 230000035945 sensitivity Effects 0.000 description 1
- 229910000030 sodium bicarbonate Inorganic materials 0.000 description 1
- 235000017557 sodium bicarbonate Nutrition 0.000 description 1
- 230000003595 spectral effect Effects 0.000 description 1
- 230000002123 temporal effect Effects 0.000 description 1
- 230000001988 toxicity Effects 0.000 description 1
- 231100000419 toxicity Toxicity 0.000 description 1
- 238000012546 transfer Methods 0.000 description 1
- XLYOFNOQVPJJNP-UHFFFAOYSA-N water Substances O XLYOFNOQVPJJNP-UHFFFAOYSA-N 0.000 description 1
- 229920001351 ε-poly-L-lysine Polymers 0.000 description 1
Images
Classifications
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
- A61K49/00—Preparations for testing in vivo
- A61K49/001—Preparation for luminescence or biological staining
- A61K49/0013—Luminescence
- A61K49/0017—Fluorescence in vivo
- A61K49/005—Fluorescence in vivo characterised by the carrier molecule carrying the fluorescent agent
- A61K49/0054—Macromolecular compounds, i.e. oligomers, polymers, dendrimers
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
- A61K49/00—Preparations for testing in vivo
- A61K49/001—Preparation for luminescence or biological staining
- A61K49/0013—Luminescence
- A61K49/0017—Fluorescence in vivo
- A61K49/0019—Fluorescence in vivo characterised by the fluorescent group, e.g. oligomeric, polymeric or dendritic molecules
- A61K49/0021—Fluorescence in vivo characterised by the fluorescent group, e.g. oligomeric, polymeric or dendritic molecules the fluorescent group being a small organic molecule
- A61K49/0032—Methine dyes, e.g. cyanine dyes
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
- A61K49/00—Preparations for testing in vivo
- A61K49/001—Preparation for luminescence or biological staining
- A61K49/0013—Luminescence
- A61K49/0017—Fluorescence in vivo
- A61K49/005—Fluorescence in vivo characterised by the carrier molecule carrying the fluorescent agent
- A61K49/0056—Peptides, proteins, polyamino acids
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
- A61K49/00—Preparations for testing in vivo
- A61K49/001—Preparation for luminescence or biological staining
- A61K49/0013—Luminescence
- A61K49/0017—Fluorescence in vivo
- A61K49/005—Fluorescence in vivo characterised by the carrier molecule carrying the fluorescent agent
- A61K49/0058—Antibodies
Landscapes
- Health & Medical Sciences (AREA)
- Life Sciences & Earth Sciences (AREA)
- Engineering & Computer Science (AREA)
- Biomedical Technology (AREA)
- Epidemiology (AREA)
- Animal Behavior & Ethology (AREA)
- General Health & Medical Sciences (AREA)
- Public Health (AREA)
- Veterinary Medicine (AREA)
- Immunology (AREA)
- Proteomics, Peptides & Aminoacids (AREA)
- Medicines Containing Antibodies Or Antigens For Use As Internal Diagnostic Agents (AREA)
- Investigating, Analyzing Materials By Fluorescence Or Luminescence (AREA)
- Peptides Or Proteins (AREA)
- Investigating Or Analysing Materials By The Use Of Chemical Reactions (AREA)
- Luminescent Compositions (AREA)
- Measuring Or Testing Involving Enzymes Or Micro-Organisms (AREA)
- Glass Compositions (AREA)
- Surface Treatment Of Glass (AREA)
- Polyesters Or Polycarbonates (AREA)
Description
本発明は、生化学、細胞生物学およびインビボにおける光学的画像形成に関する。
光学に基づいた生体医学的画像形成技法は、レーザー技術、高性能再構成アルゴリズムおよび当初はCTおよびMRIなどの非光学的断層画像形成様式のために開発された画像形成ソフトウェアの開発を含む要因により過去10年の間に進歩した。可視波長は、内視鏡および顕微鏡による表面構造の光学的画像形成に使用される。
プローブのデザインおよび合成
プローブの骨格デザインは、生体適合性(例えば、毒性および免疫原性)、血清中の半減期、有用な官能基(蛍光色素、スペーサーおよび保護基を接合するため)および費用などの考慮点に依存する。有用な種類の骨格にはポリペプチド(ポリアミノ酸)、ポリエチレンアミン、ポリサッカライド、アミノ化ポリサッカライド、アミノ化オリゴサッカライド、ポリアミドアミン、ポリアクリル酸およびポリアルコールが含まれる。好ましい骨格はL-アミノ酸から形成されるポリペプチドからなる。ポリリジンを骨格として使用する場合には、ポリリジンの側鎖のε-アミノ基が蛍光色素およびスペーサーの共有結合のための便利な反応性基として働くことができる(図1Aおよび1B)。骨格がポリペプチドである場合には、好ましくは、プローブの分子量は2 kD〜1000 kDである。さらに好ましくは、その分子量は4 kd〜500 kdである。
プローブがデザインされ、合成されたら、活性化前の分子内蛍光発光抑制の必要なレベルを解明するためにプローブをインビトロにおいて日常的に試験することができる。好ましくは、これは、希釈した生理学的緩衝液中で分子内発光抑制された蛍光色素含有プローブの蛍光地を得ることによって実施される。次いで、この値を、同じ緩衝液中で、同じ蛍光測定条件下で等しいモル濃度の遊離の蛍光色素から得られた蛍光値と比較する。好ましくは、測定が、蛍光vs.蛍光色素濃度曲線の直線部分で行われていることを明らかにするために、この比較は一連の希釈液中で実施される。
本発明は新規蛍光プローブを含むが、蛍光の一般原理、光学的画像獲得および画像処理を本発明を実施する際に適用することができる。光学的画像形成技法は、例えば、アルファノ(Alfano)ら、1997年、生物医学的培地の光学的画像形成の進歩(Advances in Optical Imaging of Biomedical Media)」、Ann. NY. Acad. Sci. 820: 248-270を参照。
本発明者らは、Cy5.5として知られる市販の蛍光色素(吸収=675 nm、発光=694 nm;アマシャム(Amersham)、イリノイ州アーリントンハイツ)をPL-MPEG(平均分子量約450 kD)に接合することによって、3種の異なる分子内発光抑制された近赤外蛍光プローブを合成した。3種のプローブはポリリジン骨格への蛍光色素の結合が異なっていた。「Cy-PL-MPEG」と命名されたプローブでは、Cy5.5は種々の密度でポリリジン側鎖のε-アミノ基に直接結合し、ε-アミノ基の誘導体化率は0.1%〜70%の範囲であった。「Cy-RRG-PL-MPEG」と命名されたプローブでは、Cy5.5蛍光色素はArg-Arg-Glyからなるスペーサーによってポリリジンに結合された。「Cy-GPICFFRLG-PL-MPEG」と命名されたプローブでは、Cy5.5蛍光色素は、Gly-Pro-Ile-Cys-Phe-Phe-Arg-Leu-Gly(配列番号:1)からなるスペーサーによってポリリジンに結合された。トリプシンおよびトリプシン様プロテアーゼは、骨格が部分的にだけ誘導体化されている場合には、Cy-PL-MPEGのポリリジン骨格を切断することができる。
機能的な画像形成用プローブを試験する際の次の段階は細胞培養実験を実施することであった。本発明者らは、取り込まれていないCy-PL-MPEGは蛍光顕微鏡によって検出不能で、細胞内取り込みによりプローブが活性化され、蛍光シグナルが得られると予測した。メラニン欠乏性B16黒色腫を使用して得られたデータは本発明者らの予測を確認しており、(1)非活性化プローブは蛍光を発光しない、(2)プローブはこの細胞株に取り込まれる、および(3)細胞内取り込みにより、プローブが活性化され、蛍光シグナルが検出されることを示した。
インビボにおけるマウス画像形成は、3つの主要な部品、光源、台/ホルダー、および画像記録装置を備えるシステムを使用して実施した。150Wハロゲンバルブを備えた光ファイバー光束(ファイバーライト(Fiberlite)高強度イルミネーターシリーズ180、ドラン-ジェネン インダストリーズ(Dolan-Jennen Industries)は広いスペクトルの白色光線を提供した。610 nm〜650 nmの範囲の均一な励起光源を形成するために、シャープなカットオフ帯域通過光フィルター(オメガ フィルター コーポ(Omega Filter Corp.)、バーモント州ブラトレボロ)を光ファイバー束の末端に取り付けた。マウス全体を均一に照射するために、光源は画像形成台の約15 cm上方に設置した。台自体は、記録装置によって反射される(および検出される可能性のある)励起光子の数を低下する皮製の黒色面とした。
Claims (32)
- ポリマー骨格と、近赤外蛍光色素による分子内蛍光発光抑制を可能にするように位置する蛍光発光抑制相互作用許容位置において該ポリマー骨格に共有結合し且つ蛍光活性化部位における酵素的切断によって分離可能な複数の近赤外蛍光色素とを含む、分子内発光抑制された蛍光画像形成プローブであって、蛍光活性化部位が、標的組織中に存在する酵素によって切断可能な結合を含み、且つポリマー骨格が、ポリペプチド、核酸、ポリサッカライド、アミノ化ポリサッカライド、アミノ化オリゴサッカライド、ポリエチレンアミン、ポリアミドアミン、ポリアクリル酸、ポリアルコール、および合成ポリマーからなる群より選択される、前記プローブ。
- 蛍光活性化部位がポリマー骨格内に位置する、請求項1記載のプローブ。
- 各蛍光色素が、蛍光活性化部位を含むスペーサーによってポリマー骨格に連結されている、請求項1記載のプローブ。
- スペーサーがオリゴペプチドである、請求項3記載のプローブ。
- 切断がトリプシン、カテプシンもしくは前立腺特異的抗原(PSA)による切断によって達成される、請求項1記載のプローブ。
- ポリペプチドがポリリジンである、請求項1記載のプローブ。
- 合成ポリマーがポリグリコール酸、ポリ乳酸、ポリ(グリコール酸−コ乳酸)、ポリジオキサノン、ポリバレロラクトン、ポリ−ε−カプロラクトン、ポリ(3-ヒドロキシブチレート)、ポリ(3-ヒドロキシバレレート)ポリタルトロン酸、およびポリ(β−マロン酸)からなる群から選択される、請求項1記載のプローブ。
- ポリマー骨格に共有結合した保護鎖をさらに含む、請求項1記載のプローブ。
- 保護鎖が、ポリエチレングリコール(PEG)、メトキシポリエチレングリコール(MPEG)、ポリエチレングリコール二酸、PEGモノアミン、MPEGモノアミン、MPEGヒドラジド、MPEGイミダゾール、メトキシポリプロピレングリコール、ポリエチレングリコールとメトキシポリプロピレングリコールのコポリマー、デキストラン、およびポリ乳酸-ポリグリコール酸からなる群より選択される、請求項8記載のプローブ。
- 蛍光色素の少なくとも1つが、650nmおよび1300nmの間の励起波長および発光波長を有する、請求項1記載のプローブ。
- 蛍光色素がCy5.5、Cy5、IRD41、IRD700、NIR-1、およびLaJolla Blueからなる群より選択される、請求項1記載のプローブ。
- 蛍光発光抑制が、自己発光抑制が誘導される密度でポリマー骨格に蛍光色素を連結することによって達成される、請求項1記載のプローブ。
- 標的化部分をさらに含む、請求項1記載のプローブ。
- 標的化部分が、共有結合または非共有結合のいずれかでプローブに結合されうる、請求項13記載のプローブ。
- 標的化部分が、抗体、抗体断片、受容体結合ポリペプチド、および受容体結合ポリサッカライドからなる群より選択される、請求項14記載のプローブ。
- 蛍光色素の少なくとも1つが近赤外蛍光色素であり、他の蛍光色素の少なくとも1つがエネルギーアクセプターである、請求項1記載のプローブ。
- エネルギーアクセプターが発光抑制蛍光色素である、請求項16記載のプローブ。
- 以下の段階を含むインビボにおける光学的画像形成方法に使用するための、請求項1記載の分子内発光抑制された蛍光プローブ:
(a) 分子内発光抑制された蛍光プローブを生きている動物またはヒトに投与する段階;
(b) 標的組織が存在する場合、標的組織内の酵素が蛍光活性化部位における酵素的切断によってプローブを活性化するだけの時間をおく段階;
(c) 蛍光色素によって吸収可能な波長の近赤外光を標的組織に照射する工程;および
(d) 蛍光色素によって放射された蛍光を検出する工程。 - インビボにおける光学的画像形成方法に使用するための、請求項1〜17のいずれか一項記載のプローブ。
- インビボにおける光学的画像形成方法が以下の段階を含む、請求項19記載のプローブ:
(a) 請求項1〜17のいずれか一項記載のプローブを被験体に投与する段階であって、ここで該プローブが標的組織に優先的に蓄積する段階;
(b) (1)プローブが標的組織に優先的に蓄積し、(2)標的組織中の酵素が蛍光活性化部位での酵素的切断によりプローブを活性化するだけの時間をおく段階;
(c)蛍光色素によって吸収可能な波長の近赤外光を被験体に照射する工程;および
(d)蛍光色素によって放射された蛍光シグナルを検出する工程。 - インビボにおける光学的画像形成方法の段階(d)で放射された蛍光シグナルが標的組織の画像形成に使用される、インビボにおける光学的画像形成方法に使用するための請求項20記載のプローブ。
- プローブの活性化が標的組織中の酵素活性に基づく、インビボにおける光学的画像形成方法に使用するための請求項19〜21のいずれか一項記載のプローブ。
- 被験体が生きている動物である、インビボにおける光学的画像形成方法に使用するための請求項19〜22のいずれか一項記載のプローブ。
- 被験体がヒトである、インビボにおける光学的画像形成方法に使用するための請求項23記載のプローブ。
- 以下の段階を含むインビボにおける光学的画像形成方法に使用するための製剤の製造における請求項1〜17のいずれか一項記載のプローブの使用:
(a) 請求項1〜17のいずれか一項記載のプローブを被験体に投与する段階であって、ここで該プローブが標的組織に優先的に蓄積する段階;
(b) (1)プローブが標的組織に優先的に蓄積し、(2)標的組織中の酵素が蛍光活性化部位での酵素的切断によりプローブを活性化するだけの時間をおく段階;
(c)蛍光色素によって吸収可能な波長の近赤外光を被験体に照射する工程;および
(d)蛍光色素によって放射された蛍光シグナルを検出する工程。 - 以下の工程を含む、インビボ光学的画像形成法:
(a)ヒト以外の被験体に請求項1〜17のいずれか一項記載のプローブを投与する工程;
(b)プローブが標的組織において活性化されるように時間をおく工程;
(c)蛍光色素によって吸収可能な波長の近赤外光を被験体に照射する工程;および
(d)蛍光色素によって放射された蛍光シグナルを検出する工程。 - 工程(a)〜(d)が時間を経て繰り返される、請求項26記載の方法。
- 工程(d)から放射された蛍光シグナルが、画像を構成するために使用される、請求項26記載の方法。
- 工程(d)が、電荷結合素子(CCD)システムまたは写真フィルムからなる適切な光検出または画像記録成分を用いて行われる、請求項26記載の方法。
- プローブ活性化の有無またはレベルが疾患状態を示す、請求項26記載の方法。
- 疾患状態が癌である、請求項30記載の方法。
- 被験体が動物生体である、請求項26記載の方法。
Applications Claiming Priority (2)
Application Number | Priority Date | Filing Date | Title |
---|---|---|---|
US09/079,447 US6083486A (en) | 1998-05-14 | 1998-05-14 | Intramolecularly-quenched near infrared fluorescent probes |
US09/079,447 | 1998-05-14 |
Related Parent Applications (1)
Application Number | Title | Priority Date | Filing Date |
---|---|---|---|
JP2000548012A Division JP4726297B2 (ja) | 1998-05-14 | 1999-05-13 | 分子内発光抑制式近赤外蛍光プローブ |
Publications (3)
Publication Number | Publication Date |
---|---|
JP2011095273A JP2011095273A (ja) | 2011-05-12 |
JP2011095273A5 JP2011095273A5 (ja) | 2012-04-05 |
JP5171970B2 true JP5171970B2 (ja) | 2013-03-27 |
Family
ID=22150620
Family Applications (2)
Application Number | Title | Priority Date | Filing Date |
---|---|---|---|
JP2000548012A Expired - Lifetime JP4726297B2 (ja) | 1998-05-14 | 1999-05-13 | 分子内発光抑制式近赤外蛍光プローブ |
JP2011005396A Expired - Lifetime JP5171970B2 (ja) | 1998-05-14 | 2011-01-14 | 分子内発光抑制式近赤外蛍光プローブ |
Family Applications Before (1)
Application Number | Title | Priority Date | Filing Date |
---|---|---|---|
JP2000548012A Expired - Lifetime JP4726297B2 (ja) | 1998-05-14 | 1999-05-13 | 分子内発光抑制式近赤外蛍光プローブ |
Country Status (9)
Country | Link |
---|---|
US (1) | US6083486A (ja) |
EP (2) | EP2251041A3 (ja) |
JP (2) | JP4726297B2 (ja) |
AT (1) | ATE473017T1 (ja) |
AU (1) | AU770216B2 (ja) |
CA (1) | CA2328136C (ja) |
DE (1) | DE69942563D1 (ja) |
HK (1) | HK1036752A1 (ja) |
WO (1) | WO1999058161A1 (ja) |
Families Citing this family (134)
Publication number | Priority date | Publication date | Assignee | Title |
---|---|---|---|---|
US7255851B2 (en) * | 1994-07-01 | 2007-08-14 | The Board Of Trustees Of The Leland Stanford Junior University | Non-invasive localization of a light-emitting conjugate in a mammal |
US7087244B2 (en) * | 2000-09-28 | 2006-08-08 | Battelle Memorial Institute | Thermogelling oligopeptide polymers |
US6592847B1 (en) * | 1998-05-14 | 2003-07-15 | The General Hospital Corporation | Intramolecularly-quenched near infrared flourescent probes |
JP2000095758A (ja) | 1998-09-18 | 2000-04-04 | Schering Ag | 近赤外蛍光造影剤および蛍光造影方法 |
US20030180221A1 (en) * | 1998-09-18 | 2003-09-25 | Schering Ag | Near infrared fluorescent contrast agent and fluorescence imaging |
US7547721B1 (en) | 1998-09-18 | 2009-06-16 | Bayer Schering Pharma Ag | Near infrared fluorescent contrast agent and fluorescence imaging |
US7107116B2 (en) * | 1999-03-29 | 2006-09-12 | Genex Technologies, Inc. | Diffuse optical tomography system and method of use |
EP1283728A2 (en) * | 2000-05-23 | 2003-02-19 | Amersham Health AS | Contrast agents |
GB0024351D0 (en) * | 2000-10-04 | 2000-11-22 | Amersham Pharm Biotech Uk Ltd | Dye-labelled peptide and method |
US6673334B1 (en) * | 2000-10-16 | 2004-01-06 | Mallinkcrodt, Inc. | Light sensitive compounds for instant determination of organ function |
US7383076B2 (en) * | 2000-11-27 | 2008-06-03 | The General Hospital Corporation | Fluorescence-mediated molecular tomography |
US6615063B1 (en) | 2000-11-27 | 2003-09-02 | The General Hospital Corporation | Fluorescence-mediated molecular tomography |
EP1379284A4 (en) * | 2001-01-05 | 2007-07-25 | Gen Hospital | ACTIVE IMAGING PROBES |
US20030044353A1 (en) * | 2001-01-05 | 2003-03-06 | Ralph Weissleder | Activatable imaging probes |
GB2372256A (en) * | 2001-02-14 | 2002-08-21 | Kalibrant Ltd | Detectable entity comprising a plurality of detectable units releasably connected together by stimulus-cleavable linkers for use in fluorescence detection |
DE10151670A1 (de) * | 2001-10-19 | 2003-05-08 | Siemens Ag | Bildgebungsverfahren und Bildgebungsvorrichtung, insbesondere für die Kleintierbildgebung |
EP1469989B1 (en) * | 2002-01-02 | 2011-12-14 | Visen Medical, Inc. | Amine functionalized superparamagnetic nanoparticles for the synthesis of bioconjugates |
WO2003061711A2 (en) * | 2002-01-16 | 2003-07-31 | Visen Medical, Inc. | Chromophore probes for optical imaging |
AU2003225763A1 (en) * | 2002-03-11 | 2003-09-29 | Visen Medical, Inc. | Optical imaging probes |
US20050249668A1 (en) * | 2002-03-29 | 2005-11-10 | Ralph Weissleder | Nir-fluorescent cyanine dyes, their synthesis and biological use |
US20040022731A1 (en) * | 2002-04-26 | 2004-02-05 | Alexei Bogdanov | In vivo imaging of apoptosis |
US7303741B2 (en) * | 2002-09-23 | 2007-12-04 | General Electric Company | Systems and methods for high-resolution in vivo imaging of biochemical activity in a living organism |
EP1481633B1 (de) * | 2003-05-30 | 2007-05-02 | Siemens Aktiengesellschaft | Gerät zum Erfassen wenigstens einer Substanz in einem Stoffwechselprozess eines Lebewesens |
WO2004108902A2 (en) * | 2003-06-04 | 2004-12-16 | Visen Medical, Inc. | Biocompatible fluorescent silicon nanoparticles |
EP1635878B1 (en) * | 2003-06-25 | 2010-12-29 | Guerbet | Peptide conjugate for magnetic resonance imaging of matrix metalloproteinases |
US20050106100A1 (en) * | 2003-09-03 | 2005-05-19 | Harris Thomas D. | Compounds containing matrix metalloproteinase substrates and methods of their use |
US7985401B2 (en) | 2003-10-31 | 2011-07-26 | The Regents Of The University Of California | Peptides whose uptake by cells is controllable |
US9695251B2 (en) | 2003-10-31 | 2017-07-04 | The Regents Of The University Of California | Activatable cell penetrating peptides with quenched fluorophores |
NO20035683D0 (no) * | 2003-12-18 | 2003-12-18 | Amersham Health As | Optisk avbildning av prostatakreft |
US20050272967A1 (en) * | 2004-05-18 | 2005-12-08 | Siemens Aktiengesellschaft | Biomolecular contrast agents with multiple signal variance for therapy planning and control in radiation therapy with proton or ion beams |
EP1747026A1 (en) * | 2004-05-18 | 2007-01-31 | Siemens Aktiengesellschaft | Biomolecular contrast agents for therapy control in radiation therapy with proton or ion beams |
US20050259779A1 (en) * | 2004-05-18 | 2005-11-24 | Siemens Aktiengesellschaft | Biomolecular contrast agents for therapy optimization in radiation therapy with proton or ion beams |
US7585492B2 (en) | 2004-05-18 | 2009-09-08 | Siemens Aktiengesellschaft | Biomolecular contrast agents for therapy success and dose monitoring in radiation therapy with proton or ion beams |
US7833513B2 (en) | 2004-12-03 | 2010-11-16 | Rhode Island Hospital | Treatment of Alzheimer's Disease |
JP2006225270A (ja) * | 2005-02-15 | 2006-08-31 | Yoshihiro Futamura | 性ホルモン修飾作用を有するトリペプチド又はそれを含有する抽出物、エイコサペンタエン酸を結合してなるトリペプチド、それからなる食品製剤、化粧品製剤、子宮内膜症治療剤 |
US20090209508A1 (en) * | 2005-05-16 | 2009-08-20 | Universite De Geneve | Compounds for Photochemotherapy |
AU2006266074A1 (en) * | 2005-06-30 | 2007-01-11 | Bristol-Myers Squibb Pharma Company | Hydrazide conjugates as imaging agents |
US8227621B2 (en) * | 2005-06-30 | 2012-07-24 | Li-Cor, Inc. | Cyanine dyes and methods of use |
EP1934202B1 (en) | 2005-09-02 | 2019-01-09 | Visen Medical, Inc. | Nicotinic acid and picolinic acid derived near-infrared fluorophores |
CA2621137C (en) * | 2005-09-02 | 2014-07-29 | Visen Medical, Inc. | Biocompatible n,n-disubstituted sulfonamide-containing fluorescent dye labels |
EP1937676B1 (en) * | 2005-09-02 | 2016-11-30 | Visen Medical, Inc. | Biocompatible fluorescent imaging agents |
EP1973575B1 (en) | 2005-12-22 | 2019-07-24 | Visen Medical, Inc. | Biocompatible fluorescent metal oxide nanoparticles |
US20070148094A1 (en) * | 2005-12-22 | 2007-06-28 | Uzgiris Egidijus E | Polymeric imaging agents and medical imaging methods |
US8478386B2 (en) | 2006-01-10 | 2013-07-02 | Accuvein Inc. | Practitioner-mounted micro vein enhancer |
US12089951B2 (en) | 2006-01-10 | 2024-09-17 | AccuVeiw, Inc. | Scanned laser vein contrast enhancer with scanning correlated to target distance |
US10813588B2 (en) | 2006-01-10 | 2020-10-27 | Accuvein, Inc. | Micro vein enhancer |
US8489178B2 (en) | 2006-06-29 | 2013-07-16 | Accuvein Inc. | Enhanced laser vein contrast enhancer with projection of analyzed vein data |
US8838210B2 (en) | 2006-06-29 | 2014-09-16 | AccuView, Inc. | Scanned laser vein contrast enhancer using a single laser |
US9492117B2 (en) | 2006-01-10 | 2016-11-15 | Accuvein, Inc. | Practitioner-mounted micro vein enhancer |
US11253198B2 (en) | 2006-01-10 | 2022-02-22 | Accuvein, Inc. | Stand-mounted scanned laser vein contrast enhancer |
US9854977B2 (en) | 2006-01-10 | 2018-01-02 | Accuvein, Inc. | Scanned laser vein contrast enhancer using a single laser, and modulation circuitry |
US11278240B2 (en) | 2006-01-10 | 2022-03-22 | Accuvein, Inc. | Trigger-actuated laser vein contrast enhancer |
US10238294B2 (en) | 2006-06-29 | 2019-03-26 | Accuvein, Inc. | Scanned laser vein contrast enhancer using one laser |
US8463364B2 (en) | 2009-07-22 | 2013-06-11 | Accuvein Inc. | Vein scanner |
US8594770B2 (en) | 2006-06-29 | 2013-11-26 | Accuvein, Inc. | Multispectral detection and presentation of an object's characteristics |
US8730321B2 (en) | 2007-06-28 | 2014-05-20 | Accuvein, Inc. | Automatic alignment of a contrast enhancement system |
US8078264B2 (en) | 2006-07-11 | 2011-12-13 | Case Western Reserve University | Intra-operative molecular imaging |
JP5864077B2 (ja) | 2006-09-08 | 2016-02-17 | ロード アイランド ホスピタル | アルコール誘発性肝疾患の治療、予防および回復 |
US9308198B2 (en) | 2006-09-08 | 2016-04-12 | Rhode Island Hospital | Treatment, prevention, and reversal of alcohol-induced brain disease |
JP2010507645A (ja) * | 2006-10-25 | 2010-03-11 | コーニンクレッカ フィリップス エレクトロニクス エヌ ヴィ | 前立腺癌を検出するための造影剤 |
US7629125B2 (en) | 2006-11-16 | 2009-12-08 | General Electric Company | Sequential analysis of biological samples |
US7741045B2 (en) * | 2006-11-16 | 2010-06-22 | General Electric Company | Sequential analysis of biological samples |
US9201063B2 (en) * | 2006-11-16 | 2015-12-01 | General Electric Company | Sequential analysis of biological samples |
ES2670852T3 (es) * | 2007-02-09 | 2018-06-01 | Visen Medical, Inc. | Colorantes con policiclo y uso de los mismos |
JP2010519320A (ja) | 2007-02-28 | 2010-06-03 | サノフィ−アベンティス | イメージングプローブ |
WO2008109832A2 (en) * | 2007-03-08 | 2008-09-12 | Visen Medical, Inc. | Viable near-infrared fluorochrome labeled cells and methods of making and using same |
US9271653B2 (en) | 2007-06-12 | 2016-03-01 | Case Western Reserve University | Intra-operative molecular imaging |
US7906106B2 (en) | 2007-06-27 | 2011-03-15 | General Electric Company | In vivo cell trafficking |
US8021647B2 (en) | 2007-06-29 | 2011-09-20 | General Electric Company | In vivo optical imaging |
CN101772577A (zh) | 2007-08-03 | 2010-07-07 | 塞诺菲-安万特股份有限公司 | 半胱天冬蛋白酶成像探针 |
JP5448397B2 (ja) * | 2007-09-07 | 2014-03-19 | キヤノン株式会社 | 基質プローブ、多重核磁気共鳴法による酵素活性の検出方法および酵素活性のイメージング方法 |
EP3320923B1 (en) | 2008-01-18 | 2022-04-06 | Visen Medical, Inc. | Fluorescent imaging agents |
US20090240138A1 (en) * | 2008-03-18 | 2009-09-24 | Steven Yi | Diffuse Optical Tomography System and Method of Use |
US20090240139A1 (en) * | 2008-03-18 | 2009-09-24 | Steven Yi | Diffuse Optical Tomography System and Method of Use |
AU2009246822B2 (en) * | 2008-03-31 | 2012-05-03 | University Of Louisville Research Foundation, Inc. | Site specific fluorescence marking and contrast marker for same |
JP5278873B2 (ja) * | 2008-05-14 | 2013-09-04 | 国立大学法人九州工業大学 | 癌診断用試薬 |
WO2010042815A2 (en) * | 2008-10-09 | 2010-04-15 | Duke University | Vhh antibody fragments for use in the detection and treatment of cancer |
US8864821B2 (en) | 2008-11-26 | 2014-10-21 | Visen Medical, Inc. | Methods and compositions for identifying subjects at risk of developing stent thrombosis |
GB0823315D0 (en) * | 2008-12-22 | 2009-01-28 | Ge Healthcare As | Fluorescent Probes |
KR101043407B1 (ko) * | 2009-02-19 | 2011-06-22 | 한국과학기술연구원 | 암 표적성이 우수한 단백질 복합체 및 이의 제조방법 |
EP2435096A1 (en) * | 2009-05-27 | 2012-04-04 | Lumicell Diagnostics, Inc. | Methods and systems for spatially identifying abnormal cells |
US9155471B2 (en) * | 2009-05-27 | 2015-10-13 | Lumicell, Inc'. | Methods and systems for spatially identifying abnormal cells |
US9682151B2 (en) | 2009-07-15 | 2017-06-20 | The Regents Of The University Of California | Peptides whose uptake in cells is controllable |
US9061109B2 (en) | 2009-07-22 | 2015-06-23 | Accuvein, Inc. | Vein scanner with user interface |
SG177763A1 (en) | 2009-07-28 | 2012-03-29 | Hoffmann La Roche | Non-invasive in vivo optical imaging method |
US8518405B2 (en) | 2009-10-08 | 2013-08-27 | The University Of North Carolina At Charlotte | Tumor specific antibodies and uses therefor |
US9677125B2 (en) * | 2009-10-21 | 2017-06-13 | General Electric Company | Detection of plurality of targets in biological samples |
BR112012028006A2 (pt) | 2010-05-07 | 2016-08-02 | Hoffmann La Roche | método de imuno-histoquímica (ihq), uso de um domínio de ligação, kit e domínio de ligação terapeuticamente ativo |
EP2609935B1 (en) * | 2010-08-23 | 2018-10-10 | Shimadzu Corporation | Switching fluorescent nanoparticle probe and fluorescent particle imaging method using same |
EP2633080B1 (en) | 2010-10-29 | 2018-12-05 | President and Fellows of Harvard College | Method of detecting targets using fluorescently labelled nucleic acid nanotube probes |
US9265844B2 (en) | 2010-12-01 | 2016-02-23 | The Methodist Hospital System | Protease degradable polypeptides and uses thereof |
US9314304B2 (en) | 2010-12-08 | 2016-04-19 | Lumicell, Inc. | Methods and system for image guided cell ablation with microscopic resolution |
WO2012118136A1 (ja) * | 2011-03-02 | 2012-09-07 | 国立大学法人京都大学 | スイッチング型蛍光ナノ粒子プローブ及びそれを用いた蛍光分子イメージング法 |
JP6100704B2 (ja) | 2011-03-07 | 2017-03-22 | エフ・ホフマン−ラ・ロシュ・アクチェンゲゼルシャフト | 治療用抗体についてのインビボ試験の手段および方法 |
EP2683413A1 (en) | 2011-03-07 | 2014-01-15 | F.Hoffmann-La Roche Ag | In vivo selection of therapeutically active antibodies |
JP6122840B2 (ja) | 2011-05-09 | 2017-04-26 | ビセン メディカル, インコーポレイテッド | 炭酸脱水酵素標的化剤およびそれの使用方法 |
WO2012159107A1 (en) | 2011-05-19 | 2012-11-22 | Rhode Island Hospital | Inhibition of renal fibrosis |
US20150031046A1 (en) * | 2011-05-24 | 2015-01-29 | Lijun Dai | Bioanalytical Reagent used in Heterogeneous Phase and Usage Method Thereof |
KR102004558B1 (ko) | 2011-07-29 | 2019-07-26 | 아벨라스 바이오사이언시즈 인코포레이티드 | 선택적 전달 분자 및 사용 방법 |
JPWO2013081036A1 (ja) * | 2011-11-29 | 2015-04-27 | 太陽誘電株式会社 | マーカ分子 |
US9375493B2 (en) | 2012-03-30 | 2016-06-28 | Visen Medical, Inc. | Bacterial imaging agents and methods of using same |
US9072426B2 (en) | 2012-08-02 | 2015-07-07 | AccuVein, Inc | Device for detecting and illuminating vasculature using an FPGA |
CN104955484B (zh) | 2012-08-15 | 2019-01-15 | 文森医学公司 | 用于前列腺癌成像的前列腺特异性抗原药剂及其使用方法 |
US20150258217A1 (en) * | 2012-10-04 | 2015-09-17 | The General Hospital Corporation | Methods of Synthesizing and Using Peg-Like Fluorochromes |
US9650674B2 (en) | 2012-10-19 | 2017-05-16 | Bioventures, Llc | Nucleic acid probes and methods of using the same |
US10548962B2 (en) | 2012-10-22 | 2020-02-04 | The Board Of Regents For Oklahoma State University | Use of the salmonella SPP type III secretion proteins as a protective vaccination |
US9950053B2 (en) | 2012-10-22 | 2018-04-24 | The Board Of Regents For Oklahoma State University | Use of the Salmonella SPP type III secretion proteins as a protective vaccination |
US10517483B2 (en) | 2012-12-05 | 2019-12-31 | Accuvein, Inc. | System for detecting fluorescence and projecting a representative image |
NL2010040C2 (en) * | 2012-12-21 | 2014-06-24 | Internat Inst For Diagnostic And Analitical Affairs B V | Cleavable coating material having microbial functionality. |
WO2014120837A2 (en) | 2013-01-29 | 2014-08-07 | The Regents Of The University Of California | Pretargeted activatable cell penetrating peptide with intracellulary releaseable prodrug |
KR102363779B1 (ko) | 2013-01-30 | 2022-02-15 | 아벨라스 바이오사이언시즈 인코포레이티드 | 선택적 전달 분자 및 사용 방법 |
US9439976B2 (en) | 2013-02-13 | 2016-09-13 | The Methodist Hospital System | Compositions and methods for using cathepsin E cleavable substrates |
JP6478971B2 (ja) | 2013-03-14 | 2019-03-06 | ルミセル, インコーポレーテッドLumicell, Inc. | 医用撮像装置 |
WO2014160037A2 (en) | 2013-03-14 | 2014-10-02 | The Regents Of The University Of California | Activatable membrane-interacting peptides and methods of use |
CA2901379C (en) | 2013-03-15 | 2023-05-16 | Visen Medical, Inc. | Substituted silaxanthenium red to near-infrared fluorochromes for in vitro and in vivo imaging and detection |
CA2901000C (en) | 2013-03-15 | 2023-03-14 | Visen Medical, Inc. | 4,4-disubstituted cyclohexyl bridged heptamethine cyanine dyes and uses thereof |
AU2014296253A1 (en) | 2013-07-30 | 2016-02-04 | President And Fellows Of Harvard College | Quantitative DNA-based imaging and super-resolution imaging |
EP3027228B1 (en) * | 2013-08-01 | 2024-10-02 | Rochester Institute of Technology | Modular imaging agents containing amino acids and peptides |
EP2848696A1 (en) | 2013-09-13 | 2015-03-18 | Sanofi-Aventis Deutschland GmbH | Caspase-1 imaging probes |
CN104673274A (zh) * | 2013-12-02 | 2015-06-03 | 复旦大学 | 一种用于肿瘤转移倾向评估的靶向示踪的酸敏感近红外荧光探针 |
EP3088898B1 (en) | 2013-12-27 | 2024-02-07 | National University Corporation Tokyo Medical and Dental University | Method for diagnosis of alzheimer's disease and frontotemporal lobar degeneration, diagnostic agent, therapeutic agent, and screening method for said agents |
KR102313982B1 (ko) | 2014-03-11 | 2021-10-18 | 프레지던트 앤드 펠로우즈 오브 하바드 칼리지 | 프로그램가능한 핵산 프로브를 이용한 고처리량 고도 다중 영상화 |
ES2830392T3 (es) | 2014-07-23 | 2021-06-03 | Ohio State Innovation Foundation | Métodos y composiciones relacionados con fragmentos de anticuerpo que se unen a la glicoproteína 72 asociada a tumores (TAG-72) |
US10385380B2 (en) | 2014-10-02 | 2019-08-20 | The Regents Of The University Of California | Personalized protease assay to measure protease activity in neoplasms |
US11370823B2 (en) | 2014-10-29 | 2022-06-28 | Massachusetts Eye And Ear Infirmary | Efficient delivery of therapeutic molecules to cells of the inner ear |
NL2013786B1 (en) * | 2014-11-13 | 2016-10-07 | Original G B V | Quenched coating. |
US10596259B2 (en) | 2015-05-20 | 2020-03-24 | The Regents Of The University Of California | Tumor radiosensitization with monomethyl auristatin E (MMAE) and derivatives thereof |
US20180224461A1 (en) | 2015-08-07 | 2018-08-09 | President And Fellows Of Harvard College | Super resolution imaging of protein-protein interactions |
CN106280533B (zh) * | 2016-08-17 | 2018-03-09 | 赣南师范大学 | 一种近红外荧光染料及其合成方法和用于寄生虫荧光标记 |
AU2017370751B2 (en) | 2016-12-09 | 2023-11-09 | Ultivue, Inc. | Improved methods for multiplex imaging using labeled nucleic acid imaging agents |
JP6977287B2 (ja) * | 2017-03-29 | 2021-12-08 | 東ソー株式会社 | 複数の蛍光物質を用いた標識方法 |
PL3630742T3 (pl) * | 2017-05-24 | 2024-04-08 | Ramot At Tel-Aviv University Ltd. | Sondy chemiluminescencyjne do obrazowania/wykrywania proteaz |
AU2019217628B2 (en) * | 2018-02-06 | 2024-09-05 | Gen-Probe Incorporated | Far-red dye probe formulations |
CN111704716B (zh) * | 2020-07-03 | 2021-07-13 | 浙江大学 | 一种荧光聚赖氨酸树枝状大分子、其制备方法和应用 |
Family Cites Families (16)
Publication number | Priority date | Publication date | Assignee | Title |
---|---|---|---|---|
AU636562B2 (en) * | 1986-12-15 | 1993-05-06 | British Technology Group Usa, Inc. | Monomeric phthalocyanine reagents |
US5384241A (en) * | 1987-09-11 | 1995-01-24 | Enzo Diagnostics, Inc. | Specific binding assay compound with inhibitive self-quenching characteristics |
EP0434858B1 (fr) * | 1989-12-27 | 1994-02-23 | Societe Des Produits Nestle S.A. | Produit de réaction d'un dextranomère greffé et d'un colorant phthalocyanine et son utilisation |
US5403928A (en) * | 1990-05-15 | 1995-04-04 | Diatron Corporation | Fluorescent marker components and fluorescent probes |
US5641878A (en) * | 1991-05-15 | 1997-06-24 | Diatron Corporation | Porphyrin, azaporphyrin, and related fluorescent dyes free of aggregation and serum binding |
CA2082934C (en) * | 1990-05-15 | 2003-08-05 | Walter B. Dandliker | Phthalocyanatopolyethylene glycol, and phthalocyanato saccharides as fluorescent digoxin reagents |
CA2082936C (en) * | 1990-05-15 | 2003-09-23 | Peter O. G. Arrhenius | Fluorescent porphyrin, and fluorescent phthalocyanine-polyethylene glycol, polyol, and saccharide derivatives as fluorescent probes |
US5846703A (en) * | 1990-05-15 | 1998-12-08 | Diatron Corporation | Fluorescence immunoassays using fluorescent dyes free of aggregation and serum binding |
AU5085793A (en) * | 1992-09-04 | 1994-03-29 | General Hospital Corporation, The | Biocompatible polymers containing diagnostic or therapeutic moieties |
DE4445065A1 (de) * | 1994-12-07 | 1996-06-13 | Diagnostikforschung Inst | Verfahren zur In-vivo-Diagnostik mittels NIR-Strahlung |
US5661035A (en) * | 1995-06-07 | 1997-08-26 | The Regents Of The University Of California | Voltage sensing by fluorescence resonance energy transfer |
DE19539409C2 (de) * | 1995-10-11 | 1999-02-18 | Diagnostikforschung Inst | Kontrastmittel für die Nahinfrarot-Diagnostik |
JP3896176B2 (ja) * | 1996-05-21 | 2007-03-22 | 浜松ホトニクス株式会社 | 近赤外線蛍光トレーサーおよび蛍光イメージング方法 |
US5928625A (en) * | 1997-03-13 | 1999-07-27 | Mallinckrodt Inc. | Method of measuring physiological function |
DE19717904A1 (de) * | 1997-04-23 | 1998-10-29 | Diagnostikforschung Inst | Säurelabile und enzymatisch spaltbare Farbstoffkonstrukte zur Diagnostik mit Nahinfrarotlicht und zur Therapie |
US5876946A (en) * | 1997-06-03 | 1999-03-02 | Pharmacopeia, Inc. | High-throughput assay |
-
1998
- 1998-05-14 US US09/079,447 patent/US6083486A/en not_active Expired - Lifetime
-
1999
- 1999-05-13 AU AU40777/99A patent/AU770216B2/en not_active Expired
- 1999-05-13 AT AT99924225T patent/ATE473017T1/de not_active IP Right Cessation
- 1999-05-13 EP EP10168642A patent/EP2251041A3/en not_active Ceased
- 1999-05-13 CA CA002328136A patent/CA2328136C/en not_active Expired - Lifetime
- 1999-05-13 EP EP99924225A patent/EP1077731B1/en not_active Expired - Lifetime
- 1999-05-13 DE DE69942563T patent/DE69942563D1/de not_active Expired - Lifetime
- 1999-05-13 JP JP2000548012A patent/JP4726297B2/ja not_active Expired - Lifetime
- 1999-05-13 WO PCT/US1999/010589 patent/WO1999058161A1/en active IP Right Grant
-
2001
- 2001-08-28 HK HK01106083.4A patent/HK1036752A1/xx not_active IP Right Cessation
-
2011
- 2011-01-14 JP JP2011005396A patent/JP5171970B2/ja not_active Expired - Lifetime
Also Published As
Publication number | Publication date |
---|---|
EP1077731B1 (en) | 2010-07-07 |
US6083486A (en) | 2000-07-04 |
WO1999058161A1 (en) | 1999-11-18 |
CA2328136A1 (en) | 1999-11-18 |
DE69942563D1 (de) | 2010-08-19 |
CA2328136C (en) | 2009-03-24 |
AU4077799A (en) | 1999-11-29 |
JP2002514610A (ja) | 2002-05-21 |
AU770216B2 (en) | 2004-02-19 |
ATE473017T1 (de) | 2010-07-15 |
EP1077731A4 (en) | 2004-05-12 |
EP2251041A3 (en) | 2010-12-01 |
EP1077731A1 (en) | 2001-02-28 |
JP4726297B2 (ja) | 2011-07-20 |
EP2251041A2 (en) | 2010-11-17 |
JP2011095273A (ja) | 2011-05-12 |
HK1036752A1 (en) | 2002-01-18 |
Similar Documents
Publication | Publication Date | Title |
---|---|---|
JP5171970B2 (ja) | 分子内発光抑制式近赤外蛍光プローブ | |
US6592847B1 (en) | Intramolecularly-quenched near infrared flourescent probes | |
Bremer et al. | Optical-based molecular imaging: contrast agents and potential medical applications | |
JP4699575B2 (ja) | 化合物 | |
Bogdanov Jr et al. | Cellular activation of the self-quenched fluorescent reporter probe in tumor microenvironment | |
US20030044353A1 (en) | Activatable imaging probes | |
CN110741242B (zh) | 比率荧光成像方法 | |
Ferber et al. | Polymeric nanotheranostics for real-time non-invasive optical imaging of breast cancer progression and drug release | |
WO2002056670A2 (en) | Activatable imaging probes | |
WO2007109364A2 (en) | Intramolecularly quenched fluorochrome conjugates and methods of use | |
CA2961095C (en) | Upar targeting peptide for use in perioperative optical imaging of invasive cancer | |
Napp et al. | Optical imaging in vivo with a focus on paediatric disease: technical progress, current preclinical and clinical applications and future perspectives | |
US20060147378A1 (en) | Azulene dimer-quenched, near-infrared fluorescent probes | |
CN102325551A (zh) | 具有聚合物骨架的荧光探针 | |
Özel et al. | Enzymatically activated near infrared nanoprobes based on amphiphilic block copolymers for optical detection of cancer | |
Schmidt et al. | Near-infrared II fluorescence imaging | |
US20090074672A1 (en) | Tumor Boundary Imaging | |
Akers et al. | Biological applications of fluorescence lifetime imaging beyond microscopy | |
Bogdanov et al. | Fluorescent macromolecular sensors of enzymatic activity for in vivo imaging | |
Moin et al. | Fluorescent imaging of tumors | |
Eisenblätter et al. | Optical and Optoacoustic Imaging Probes | |
Bornhop et al. | Fluorescent Probes in Biomedical Applications | |
Jaffer et al. | Molecular Imaging of Cancer Using Fluorescent Probe Technology | |
López | Mechanism of Near-Infrared Fluorescent Signal Generation in Proteolysis-Sensitive Macromolecular Imaging Probes | |
Vo-Dinh | Fluorescent Probes in Biomedical Applications |
Legal Events
Date | Code | Title | Description |
---|---|---|---|
A521 | Request for written amendment filed |
Free format text: JAPANESE INTERMEDIATE CODE: A523 Effective date: 20120208 |
|
A131 | Notification of reasons for refusal |
Free format text: JAPANESE INTERMEDIATE CODE: A131 Effective date: 20120509 |
|
A601 | Written request for extension of time |
Free format text: JAPANESE INTERMEDIATE CODE: A601 Effective date: 20120808 |
|
A602 | Written permission of extension of time |
Free format text: JAPANESE INTERMEDIATE CODE: A602 Effective date: 20120813 |
|
A521 | Request for written amendment filed |
Free format text: JAPANESE INTERMEDIATE CODE: A523 Effective date: 20121109 |
|
A01 | Written decision to grant a patent or to grant a registration (utility model) |
Free format text: JAPANESE INTERMEDIATE CODE: A01 Effective date: 20121203 |
|
A61 | First payment of annual fees (during grant procedure) |
Free format text: JAPANESE INTERMEDIATE CODE: A61 Effective date: 20121225 |
|
R250 | Receipt of annual fees |
Free format text: JAPANESE INTERMEDIATE CODE: R250 |
|
R250 | Receipt of annual fees |
Free format text: JAPANESE INTERMEDIATE CODE: R250 |
|
R250 | Receipt of annual fees |
Free format text: JAPANESE INTERMEDIATE CODE: R250 |
|
R250 | Receipt of annual fees |
Free format text: JAPANESE INTERMEDIATE CODE: R250 |
|
EXPY | Cancellation because of completion of term |