CN105214103B - For malignant tumour and the metal ion reagent and image preparation of the quick detection of cardiovascular and cerebrovascular relevant disease early stage and multi-modality imaging - Google Patents
For malignant tumour and the metal ion reagent and image preparation of the quick detection of cardiovascular and cerebrovascular relevant disease early stage and multi-modality imaging Download PDFInfo
- Publication number
- CN105214103B CN105214103B CN201510667003.5A CN201510667003A CN105214103B CN 105214103 B CN105214103 B CN 105214103B CN 201510667003 A CN201510667003 A CN 201510667003A CN 105214103 B CN105214103 B CN 105214103B
- Authority
- CN
- China
- Prior art keywords
- ion
- metal ion
- reagent
- metal
- cardiovascular
- 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.)
- Active
Links
- 229910021645 metal ion Inorganic materials 0.000 title claims abstract description 138
- 239000003153 chemical reaction reagent Substances 0.000 title claims abstract description 111
- 238000003384 imaging method Methods 0.000 title claims abstract description 51
- 238000002360 preparation method Methods 0.000 title claims abstract description 46
- 201000011510 cancer Diseases 0.000 title claims abstract description 33
- 238000001514 detection method Methods 0.000 title claims abstract description 27
- 208000037265 diseases, disorders, signs and symptoms Diseases 0.000 title claims abstract description 24
- 201000010099 disease Diseases 0.000 title claims abstract description 23
- 230000002526 effect on cardiovascular system Effects 0.000 title claims abstract description 23
- -1 iron ion Chemical class 0.000 claims abstract description 64
- 230000003902 lesion Effects 0.000 claims abstract description 38
- XEEYBQQBJWHFJM-UHFFFAOYSA-N iron Substances [Fe] XEEYBQQBJWHFJM-UHFFFAOYSA-N 0.000 claims abstract description 24
- 229910052742 iron Inorganic materials 0.000 claims abstract description 24
- CWYNVVGOOAEACU-UHFFFAOYSA-N Fe2+ Chemical compound [Fe+2] CWYNVVGOOAEACU-UHFFFAOYSA-N 0.000 claims abstract description 23
- 229910001448 ferrous ion Inorganic materials 0.000 claims abstract description 20
- 238000011065 in-situ storage Methods 0.000 claims abstract description 13
- 239000010970 precious metal Substances 0.000 claims abstract description 11
- 229910052761 rare earth metal Inorganic materials 0.000 claims abstract description 11
- 229910001428 transition metal ion Inorganic materials 0.000 claims abstract description 11
- 239000007864 aqueous solution Substances 0.000 claims abstract description 10
- 239000000203 mixture Substances 0.000 claims abstract description 9
- PTFCDOFLOPIGGS-UHFFFAOYSA-N Zinc dication Chemical compound [Zn+2] PTFCDOFLOPIGGS-UHFFFAOYSA-N 0.000 claims abstract description 8
- 229910052684 Cerium Inorganic materials 0.000 claims abstract description 6
- 208000019065 cervical carcinoma Diseases 0.000 claims description 13
- 208000006011 Stroke Diseases 0.000 claims description 12
- 201000007270 liver cancer Diseases 0.000 claims description 11
- 208000014018 liver neoplasm Diseases 0.000 claims description 11
- 206010012289 Dementia Diseases 0.000 claims description 9
- 229910052737 gold Inorganic materials 0.000 claims description 9
- 239000010931 gold Substances 0.000 claims description 9
- 229910052693 Europium Inorganic materials 0.000 claims description 8
- 150000002500 ions Chemical class 0.000 claims description 8
- 208000032839 leukemia Diseases 0.000 claims description 7
- 206010008190 Cerebrovascular accident Diseases 0.000 claims description 5
- 230000002490 cerebral effect Effects 0.000 claims description 5
- 239000002872 contrast media Substances 0.000 claims description 3
- 229910052697 platinum Inorganic materials 0.000 claims description 3
- BASFCYQUMIYNBI-UHFFFAOYSA-N platinum Substances [Pt] BASFCYQUMIYNBI-UHFFFAOYSA-N 0.000 claims description 3
- 208000003174 Brain Neoplasms Diseases 0.000 claims description 2
- 206010058467 Lung neoplasm malignant Diseases 0.000 claims description 2
- FYYHWMGAXLPEAU-UHFFFAOYSA-N Magnesium Chemical compound [Mg] FYYHWMGAXLPEAU-UHFFFAOYSA-N 0.000 claims description 2
- 230000015572 biosynthetic process Effects 0.000 claims description 2
- 201000005202 lung cancer Diseases 0.000 claims description 2
- 208000020816 lung neoplasm Diseases 0.000 claims description 2
- 229910052749 magnesium Inorganic materials 0.000 claims description 2
- 239000011777 magnesium Substances 0.000 claims description 2
- 201000008968 osteosarcoma Diseases 0.000 claims description 2
- 238000003786 synthesis reaction Methods 0.000 claims description 2
- 239000012216 imaging agent Substances 0.000 claims 1
- 229910052746 lanthanum Inorganic materials 0.000 claims 1
- FZLIPJUXYLNCLC-UHFFFAOYSA-N lanthanum atom Chemical compound [La] FZLIPJUXYLNCLC-UHFFFAOYSA-N 0.000 claims 1
- 229910052709 silver Inorganic materials 0.000 claims 1
- 239000004332 silver Substances 0.000 claims 1
- 230000000694 effects Effects 0.000 abstract description 7
- JLVVSXFLKOJNIY-UHFFFAOYSA-N Magnesium ion Chemical compound [Mg+2] JLVVSXFLKOJNIY-UHFFFAOYSA-N 0.000 abstract description 6
- 229910001425 magnesium ion Inorganic materials 0.000 abstract description 6
- 238000012544 monitoring process Methods 0.000 abstract description 3
- 239000000700 radioactive tracer Substances 0.000 abstract description 3
- 231100000331 toxic Toxicity 0.000 abstract description 3
- 230000002588 toxic effect Effects 0.000 abstract description 3
- CVOFKRWYWCSDMA-UHFFFAOYSA-N 2-chloro-n-(2,6-diethylphenyl)-n-(methoxymethyl)acetamide;2,6-dinitro-n,n-dipropyl-4-(trifluoromethyl)aniline Chemical compound CCC1=CC=CC(CC)=C1N(COC)C(=O)CCl.CCCN(CCC)C1=C([N+]([O-])=O)C=C(C(F)(F)F)C=C1[N+]([O-])=O CVOFKRWYWCSDMA-UHFFFAOYSA-N 0.000 abstract description 2
- 206010028980 Neoplasm Diseases 0.000 description 97
- 241000699666 Mus <mouse, genus> Species 0.000 description 92
- 238000004458 analytical method Methods 0.000 description 57
- 238000002595 magnetic resonance imaging Methods 0.000 description 34
- 230000008859 change Effects 0.000 description 25
- 238000000799 fluorescence microscopy Methods 0.000 description 22
- 230000008685 targeting Effects 0.000 description 19
- 238000000034 method Methods 0.000 description 17
- 239000000243 solution Substances 0.000 description 17
- 241000699660 Mus musculus Species 0.000 description 16
- 238000011580 nude mouse model Methods 0.000 description 16
- 238000013170 computed tomography imaging Methods 0.000 description 15
- 239000000696 magnetic material Substances 0.000 description 14
- 239000000463 material Substances 0.000 description 14
- 230000009467 reduction Effects 0.000 description 13
- 229910021642 ultra pure water Inorganic materials 0.000 description 12
- 239000012498 ultrapure water Substances 0.000 description 12
- 241001465754 Metazoa Species 0.000 description 11
- 210000001124 body fluid Anatomy 0.000 description 11
- 239000010839 body fluid Substances 0.000 description 11
- 238000002156 mixing Methods 0.000 description 11
- 210000002700 urine Anatomy 0.000 description 11
- 210000003462 vein Anatomy 0.000 description 11
- 206010002091 Anaesthesia Diseases 0.000 description 10
- PIWKPBJCKXDKJR-UHFFFAOYSA-N Isoflurane Chemical compound FC(F)OC(Cl)C(F)(F)F PIWKPBJCKXDKJR-UHFFFAOYSA-N 0.000 description 10
- 230000037005 anaesthesia Effects 0.000 description 10
- 229960002725 isoflurane Drugs 0.000 description 10
- 238000004451 qualitative analysis Methods 0.000 description 10
- 238000004445 quantitative analysis Methods 0.000 description 10
- 150000001875 compounds Chemical class 0.000 description 7
- 210000004369 blood Anatomy 0.000 description 6
- 239000008280 blood Substances 0.000 description 6
- 239000003795 chemical substances by application Substances 0.000 description 6
- 210000002966 serum Anatomy 0.000 description 6
- SQGYOTSLMSWVJD-UHFFFAOYSA-N silver(1+) nitrate Chemical compound [Ag+].[O-]N(=O)=O SQGYOTSLMSWVJD-UHFFFAOYSA-N 0.000 description 6
- 230000003313 weakening effect Effects 0.000 description 6
- 238000000862 absorption spectrum Methods 0.000 description 5
- 238000002484 cyclic voltammetry Methods 0.000 description 5
- 230000006378 damage Effects 0.000 description 5
- 238000000835 electrochemical detection Methods 0.000 description 5
- 238000005516 engineering process Methods 0.000 description 5
- WLYAEQLCCOGBPV-UHFFFAOYSA-N europium;sulfuric acid Chemical compound [Eu].OS(O)(=O)=O WLYAEQLCCOGBPV-UHFFFAOYSA-N 0.000 description 5
- 238000001506 fluorescence spectroscopy Methods 0.000 description 5
- FDWREHZXQUYJFJ-UHFFFAOYSA-M gold monochloride Chemical compound [Cl-].[Au+] FDWREHZXQUYJFJ-UHFFFAOYSA-M 0.000 description 5
- 238000000338 in vitro Methods 0.000 description 5
- 230000004060 metabolic process Effects 0.000 description 5
- 229910052751 metal Inorganic materials 0.000 description 5
- 239000002184 metal Substances 0.000 description 5
- 230000003287 optical effect Effects 0.000 description 5
- 239000002245 particle Substances 0.000 description 5
- 238000012360 testing method Methods 0.000 description 5
- JIAARYAFYJHUJI-UHFFFAOYSA-L zinc dichloride Chemical compound [Cl-].[Cl-].[Zn+2] JIAARYAFYJHUJI-UHFFFAOYSA-L 0.000 description 5
- 229960000306 zinc gluconate Drugs 0.000 description 5
- 235000011478 zinc gluconate Nutrition 0.000 description 5
- 239000011670 zinc gluconate Substances 0.000 description 5
- 208000024827 Alzheimer disease Diseases 0.000 description 4
- ZAMOUSCENKQFHK-UHFFFAOYSA-N Chlorine atom Chemical compound [Cl] ZAMOUSCENKQFHK-UHFFFAOYSA-N 0.000 description 4
- 229910021578 Iron(III) chloride Inorganic materials 0.000 description 4
- 206010039966 Senile dementia Diseases 0.000 description 4
- FOIXSVOLVBLSDH-UHFFFAOYSA-N Silver ion Chemical compound [Ag+] FOIXSVOLVBLSDH-UHFFFAOYSA-N 0.000 description 4
- 239000000460 chlorine Substances 0.000 description 4
- 229910052801 chlorine Inorganic materials 0.000 description 4
- 230000005284 excitation Effects 0.000 description 4
- 239000004744 fabric Substances 0.000 description 4
- 229960002089 ferrous chloride Drugs 0.000 description 4
- NMCUIPGRVMDVDB-UHFFFAOYSA-L iron dichloride Chemical compound Cl[Fe]Cl NMCUIPGRVMDVDB-UHFFFAOYSA-L 0.000 description 4
- RBTARNINKXHZNM-UHFFFAOYSA-K iron trichloride Chemical compound Cl[Fe](Cl)Cl RBTARNINKXHZNM-UHFFFAOYSA-K 0.000 description 4
- 235000005074 zinc chloride Nutrition 0.000 description 4
- 239000011592 zinc chloride Substances 0.000 description 4
- 208000027418 Wounds and injury Diseases 0.000 description 3
- HCHKCACWOHOZIP-UHFFFAOYSA-N Zinc Chemical compound [Zn] HCHKCACWOHOZIP-UHFFFAOYSA-N 0.000 description 3
- WHMDKBIGKVEYHS-IYEMJOQQSA-L Zinc gluconate Chemical compound [Zn+2].OC[C@@H](O)[C@@H](O)[C@H](O)[C@@H](O)C([O-])=O.OC[C@@H](O)[C@@H](O)[C@H](O)[C@@H](O)C([O-])=O WHMDKBIGKVEYHS-IYEMJOQQSA-L 0.000 description 3
- 210000004204 blood vessel Anatomy 0.000 description 3
- 208000014674 injury Diseases 0.000 description 3
- 239000002086 nanomaterial Substances 0.000 description 3
- 150000002910 rare earth metals Chemical class 0.000 description 3
- 229910001961 silver nitrate Inorganic materials 0.000 description 3
- 239000011701 zinc Substances 0.000 description 3
- 229910052725 zinc Inorganic materials 0.000 description 3
- QGZKDVFQNNGYKY-UHFFFAOYSA-N Ammonia Chemical compound N QGZKDVFQNNGYKY-UHFFFAOYSA-N 0.000 description 2
- 230000000052 comparative effect Effects 0.000 description 2
- 238000003745 diagnosis Methods 0.000 description 2
- OGPBJKLSAFTDLK-UHFFFAOYSA-N europium atom Chemical compound [Eu] OGPBJKLSAFTDLK-UHFFFAOYSA-N 0.000 description 2
- GAGGCOKRLXYWIV-UHFFFAOYSA-N europium(3+);trinitrate Chemical compound [Eu+3].[O-][N+]([O-])=O.[O-][N+]([O-])=O.[O-][N+]([O-])=O GAGGCOKRLXYWIV-UHFFFAOYSA-N 0.000 description 2
- PCHJSUWPFVWCPO-UHFFFAOYSA-N gold Chemical compound [Au] PCHJSUWPFVWCPO-UHFFFAOYSA-N 0.000 description 2
- 238000002347 injection Methods 0.000 description 2
- 239000007924 injection Substances 0.000 description 2
- FBAFATDZDUQKNH-UHFFFAOYSA-M iron chloride Chemical compound [Cl-].[Fe] FBAFATDZDUQKNH-UHFFFAOYSA-M 0.000 description 2
- VCJMYUPGQJHHFU-UHFFFAOYSA-N iron(3+);trinitrate Chemical compound [Fe+3].[O-][N+]([O-])=O.[O-][N+]([O-])=O.[O-][N+]([O-])=O VCJMYUPGQJHHFU-UHFFFAOYSA-N 0.000 description 2
- CZMAIROVPAYCMU-UHFFFAOYSA-N lanthanum(3+) Chemical compound [La+3] CZMAIROVPAYCMU-UHFFFAOYSA-N 0.000 description 2
- 150000002739 metals Chemical class 0.000 description 2
- 238000002600 positron emission tomography Methods 0.000 description 2
- 102000004169 proteins and genes Human genes 0.000 description 2
- 108090000623 proteins and genes Proteins 0.000 description 2
- XLYOFNOQVPJJNP-UHFFFAOYSA-N water Substances O XLYOFNOQVPJJNP-UHFFFAOYSA-N 0.000 description 2
- ONDPHDOFVYQSGI-UHFFFAOYSA-N zinc nitrate Chemical compound [Zn+2].[O-][N+]([O-])=O.[O-][N+]([O-])=O ONDPHDOFVYQSGI-UHFFFAOYSA-N 0.000 description 2
- 208000019838 Blood disease Diseases 0.000 description 1
- VEXZGXHMUGYJMC-UHFFFAOYSA-M Chloride anion Chemical compound [Cl-] VEXZGXHMUGYJMC-UHFFFAOYSA-M 0.000 description 1
- 229910003803 Gold(III) chloride Inorganic materials 0.000 description 1
- 206010019196 Head injury Diseases 0.000 description 1
- 206010021143 Hypoxia Diseases 0.000 description 1
- 229910002651 NO3 Inorganic materials 0.000 description 1
- NHNBFGGVMKEFGY-UHFFFAOYSA-N Nitrate Chemical compound [O-][N+]([O-])=O NHNBFGGVMKEFGY-UHFFFAOYSA-N 0.000 description 1
- SJUCACGNNJFHLB-UHFFFAOYSA-N O=C1N[ClH](=O)NC2=C1NC(=O)N2 Chemical compound O=C1N[ClH](=O)NC2=C1NC(=O)N2 SJUCACGNNJFHLB-UHFFFAOYSA-N 0.000 description 1
- 238000001237 Raman spectrum Methods 0.000 description 1
- ZBGLGVFYHCSILI-UHFFFAOYSA-N acetic acid;europium Chemical compound [Eu].CC(O)=O ZBGLGVFYHCSILI-UHFFFAOYSA-N 0.000 description 1
- 229910021529 ammonia Inorganic materials 0.000 description 1
- 230000009286 beneficial effect Effects 0.000 description 1
- 230000008901 benefit Effects 0.000 description 1
- 230000000975 bioactive effect Effects 0.000 description 1
- VGBWDOLBWVJTRZ-UHFFFAOYSA-K cerium(3+);triacetate Chemical compound [Ce+3].CC([O-])=O.CC([O-])=O.CC([O-])=O VGBWDOLBWVJTRZ-UHFFFAOYSA-K 0.000 description 1
- HSJPMRKMPBAUAU-UHFFFAOYSA-N cerium(3+);trinitrate Chemical compound [Ce+3].[O-][N+]([O-])=O.[O-][N+]([O-])=O.[O-][N+]([O-])=O HSJPMRKMPBAUAU-UHFFFAOYSA-N 0.000 description 1
- VZDYWEUILIUIDF-UHFFFAOYSA-J cerium(4+);disulfate Chemical compound [Ce+4].[O-]S([O-])(=O)=O.[O-]S([O-])(=O)=O VZDYWEUILIUIDF-UHFFFAOYSA-J 0.000 description 1
- 229910000355 cerium(IV) sulfate Inorganic materials 0.000 description 1
- 238000005660 chlorination reaction Methods 0.000 description 1
- 230000007547 defect Effects 0.000 description 1
- 238000002059 diagnostic imaging Methods 0.000 description 1
- 238000002405 diagnostic procedure Methods 0.000 description 1
- 238000013399 early diagnosis Methods 0.000 description 1
- 235000013399 edible fruits Nutrition 0.000 description 1
- SULCVUWEGVSCPF-UHFFFAOYSA-L europium(2+);carbonate Chemical compound [Eu+2].[O-]C([O-])=O SULCVUWEGVSCPF-UHFFFAOYSA-L 0.000 description 1
- NNMXSTWQJRPBJZ-UHFFFAOYSA-K europium(iii) chloride Chemical compound Cl[Eu](Cl)Cl NNMXSTWQJRPBJZ-UHFFFAOYSA-K 0.000 description 1
- 238000002474 experimental method Methods 0.000 description 1
- RJHLTVSLYWWTEF-UHFFFAOYSA-K gold trichloride Chemical compound Cl[Au](Cl)Cl RJHLTVSLYWWTEF-UHFFFAOYSA-K 0.000 description 1
- 229940076131 gold trichloride Drugs 0.000 description 1
- 229910021505 gold(III) hydroxide Inorganic materials 0.000 description 1
- 230000012010 growth Effects 0.000 description 1
- 230000036541 health Effects 0.000 description 1
- 208000014951 hematologic disease Diseases 0.000 description 1
- 208000018706 hematopoietic system disease Diseases 0.000 description 1
- 238000001727 in vivo Methods 0.000 description 1
- 206010061289 metastatic neoplasm Diseases 0.000 description 1
- 230000004048 modification Effects 0.000 description 1
- 238000012986 modification Methods 0.000 description 1
- 210000000865 mononuclear phagocyte system Anatomy 0.000 description 1
- 231100000915 pathological change Toxicity 0.000 description 1
- 230000036285 pathological change Effects 0.000 description 1
- 230000007170 pathology Effects 0.000 description 1
- 230000008569 process Effects 0.000 description 1
- 238000011160 research Methods 0.000 description 1
- 238000002603 single-photon emission computed tomography Methods 0.000 description 1
- 230000002269 spontaneous effect Effects 0.000 description 1
- 239000003381 stabilizer Substances 0.000 description 1
- 238000004416 surface enhanced Raman spectroscopy Methods 0.000 description 1
- 230000004083 survival effect Effects 0.000 description 1
- 230000001360 synchronised effect Effects 0.000 description 1
- 238000002626 targeted therapy Methods 0.000 description 1
- 231100000419 toxicity Toxicity 0.000 description 1
- 230000001988 toxicity Effects 0.000 description 1
- 230000004614 tumor growth Effects 0.000 description 1
- 239000000439 tumor marker Substances 0.000 description 1
- 238000002604 ultrasonography Methods 0.000 description 1
- 230000000007 visual effect Effects 0.000 description 1
- NWONKYPBYAMBJT-UHFFFAOYSA-L zinc sulfate Chemical compound [Zn+2].[O-]S([O-])(=O)=O NWONKYPBYAMBJT-UHFFFAOYSA-L 0.000 description 1
- 229960001763 zinc sulfate Drugs 0.000 description 1
- 229910000368 zinc sulfate Inorganic materials 0.000 description 1
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
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
- A61K49/00—Preparations for testing in vivo
- A61K49/04—X-ray contrast preparations
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
- A61K49/00—Preparations for testing in vivo
- A61K49/06—Nuclear magnetic resonance [NMR] contrast preparations; Magnetic resonance imaging [MRI] contrast preparations
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
- A61K49/00—Preparations for testing in vivo
- A61K49/22—Echographic preparations; Ultrasound imaging preparations ; Optoacoustic imaging preparations
Landscapes
- Health & Medical Sciences (AREA)
- Public Health (AREA)
- Epidemiology (AREA)
- Life Sciences & Earth Sciences (AREA)
- Animal Behavior & Ethology (AREA)
- General Health & Medical Sciences (AREA)
- Veterinary Medicine (AREA)
- Nuclear Medicine, Radiotherapy & Molecular Imaging (AREA)
- Radiology & Medical Imaging (AREA)
- Acoustics & Sound (AREA)
- Physics & Mathematics (AREA)
- Medicines Containing Antibodies Or Antigens For Use As Internal Diagnostic Agents (AREA)
- Magnetic Resonance Imaging Apparatus (AREA)
Abstract
It is used for malignant tumour and the metal ion reagent and image preparation of the quick detection of cardiovascular and cerebrovascular relevant disease early stage and multi-modality imaging the invention discloses a kind of.The metal ion reagent is the aqueous solution of metal ion, and metal ion is formulated by least one of iron ion or ferrous ion and magnesium ion, transition metal ions, rare earth ion and precious metal ion；Transition metal ions is the mixture of one or both of cerium ion, zinc ion；The molar ratio of iron ion or ferrous ion and other metal ions is 5~1:1.Image preparation is synthesized by metal ion reagent in lesions position by biology in situ effect fixed point.Metal ion reagent of the present invention can in sick cell fabricated in situ multi-modality imaging image preparation, can non-intrusion type highly sensitive quick tracer dynamic in real time is carried out to lesions position and monitoring, inanimate object toxic side effect, detection method are simple and easy to do.
Description
Technical field
The present invention relates to medical imaging field, more particularly to one kind to be used for malignant tumour and cardiovascular and cerebrovascular relevant disease early stage
Quick detection and the metal ion reagent and image preparation of multi-modality imaging.
Background technology
Cancer, also known as malignant tumour, have become the maximum killer of 21st century influence human body health and life.
In clinical treatment work, the discovery of malignant tumour depends on the Examined effects such as iconography, pathology and conventional tumor-marker.
The existing Imaging Method for being usually used in diagnosing tumour mainly includes MRI (Magnetic resonance imaging), and SPECT (break by single photon emission
Layer imaging), PET (positron emission tomography), these methods have certain limitation, though clinically using more
Year, but lack enough susceptibility and specificity, it is often more important that be difficult to early detection tumour.If can early detection canceration site
And it is so far for one of most effective treatment method of cancer to carry out targeted therapy to it in time.In order to improve tumor patient
Survival rate and quality of life, study more advanced diagnostic method and preparation, come realize it is accurate, timely early diagnosis of cancer and
Treatment is always one of direction that people make great efforts.
With deepening continuously for biomedical research, visual bio-imaging technology is played the part of in life science and medical domain
More and more important role is drilled, for other bio-imaging technologies, fluorescence imaging has cheap, Imaging fast
The characteristics of, and the sensitiveness single molecular imaging with molecular level, and the growth of tumour can be marked and traced.In addition,
Imaging-PAM can measure the tumour growth situation of various cancer models, monitor cancer cell in treatment of cancer in real time
Change；The quantitative detection that hurtless measure ground is carried out to mouse entirety primary tumor, metastatic tumor and Spontaneous Tumor.
The multi-modality imaging that fluorescence imaging is combined with CT imagings, Magnetic resonance imaging, ultrasonic imaging and photoelectronic imaging
Technology, can effectively utilize the advantage of various imaging techniques, learn from other's strong points to offset one's weaknesses, early stage malignant tumour, real-time, quick diagnosis
In there is huge application prospect.But how to search out a kind of multi-modality imaging system that can be used for several imaging means at the same time
Agent also becomes new challenge, and the targeting of many problems such as preparation is bad, and toxicity in vivo is big, stability difference and internal
The weak grade of signal strength is all urgently to be resolved hurrily.
The content of the invention
Goal of the invention：For the existing a variety of technologies for being directed to malignant tumour and cardiovascular and cerebrovascular relevant disease early detection
Defect, the present invention provides a kind of for malignant tumour and the quick detection of cardiovascular and cerebrovascular relevant disease early stage and multi-modality imaging
Metal ion reagent, the metal ion reagent can in the sick cells such as tumour fabricated in situ be used for multi-modality imaging image
Preparation, can non-intrusion type carry out dynamic in real time highly sensitive quick tracer and monitoring to lesions position, realize to malignant tumour
Detected with cardiovascular and cerebrovascular relevant disease early stage, quick, multi-modality imaging, and inanimate object toxic side effect, detection method are simple and easy to do.
To reach above-mentioned purpose, the present invention is achieved by the following technical solutions：
It is of the present invention for malignant tumour and the quick detection of cardiovascular and cerebrovascular relevant disease early stage and multi-modality imaging
Metal ion reagent, it is the aqueous solution containing metal ion, the metal ion by iron ion or ferrous ion and magnesium from
At least one of son, transition metal ions, rare earth ion and precious metal ion are formulated；Wherein, the transition
Metal ion is the mixture of one or both of cerium ion, zinc ion；In metal ion reagent, iron ion or ferrous ion
Molar ratio with other metal ions is 5~1:1.
Contain ferrous ion or iron ion in metal ion reagent of the present invention, ferrous ion or iron ion and other metals from
Son, which is engaged, to play a role, other metal ions are in magnesium ion, transition metal ions, rare earth ion and precious metal ion
At least one.It will be understood by those skilled in the art that in metal ion reagent, iron ion or ferrous ion and other metals from
The molar ratio of son is 5~1:1, herein, be using iron ion in metal ion reagent or the metal ion beyond ferrous ion as
Entirety calculates.
The rare earth ion is the mixture of one or both of europium ion, lanthanum ion.
The precious metal ion is the mixture of one or both of gold ion, silver ion, platinum ion.
Preferably, the metal ion is by iron ion or ferrous ion and magnesium ion, transition metal ions, rare earth metal
One or both of ion and precious metal ion are formulated.
Preferably, the metal ion by iron ion or ferrous ion and magnesium ion, cerium ion, zinc ion, europium ion,
One or both of lanthanum ion, gold ion, silver ion, platinum ion are formulated.Further, the metal ion combination of preparation
Can be iron ion, europium ion and zinc ion；Zinc ion, gold ion and ferrous ion；Europium ion and ferrous ion；Gold ion,
Silver ion and iron ion；Zinc ion and ferrous ion；Deng.
Preferably, in metal ion reagent, the concentration of iron ion or ferrous ion is 5~10mmol/L.Metal ion tries
The concentration and usage amount of agent are according to using depending on object.
In the metal ion reagent of the present invention, metal ion is carried by the compound of water-soluble ion containing respective metal
For e.g., cerium ion is provided by soluble compound containing cerium ion such as cerous acetate, cerous nitrate, ceric sulfate etc.；Zinc ion is by can
Such as zinc chloride, zinc nitrate, zinc gluconate, zinc sulfate etc. containing zinc ion compound of dissolubility provide；Gold ion is by solubility
Compound containing gold ion such as gold chloride, eight chlorinations, four gold medal, chlorauride, gold trichloride, gold monochloride etc. provide；Silver ion is by can
Such as silver-colored ammonia of the Ag-containing compound of dissolubility, silver nitrate provide；Europium is by the soluble compound containing europium ion such as europium nitrate, sulfuric acid
Europium, Europium chloride, europium, europium carbonate, acetic acid europium etc. provide；Iron ion or ferrous ion contain iron ion or ferrous iron by soluble
The compound of ion such as ferric nitrate, iron chloride, ferrous nitrate, frerrous chloride etc. provide.
The metal ion reagent of the present invention is dissolved in water by the compound of metal ion and is made, and water can use ultra-pure water.Tool
It is as follows that body prepares measure：
By other metal ion (magnesium ion, transition metal ions, precious metal ion and rare earth ions, according to specific
Formula make choice) be dissolved in ultra-pure water respectively, be configured to certain concentration (5~10mmol).By other metal ion (mistakes
Cross metal ion, precious metal ion and rare earth ion) with iron ion or ferrous ions soln according to volume ratio 1:1 to 1:5
Between ratio mixing be dissolved in ultra-pure water, be configured to certain concentration (5~10mmol).
Using prepared other metal ions (magnesium ion, transition metal ions, precious metal ion and rare earth metal from
Son) body fluid (such as blood or serum) or urine are tested with the hybrid detection reagent of iron ion or ferrous ion, tie
Fruit shows, the optics and electrochemical properties of malignant tumour and cardiovascular and cerebrovascular relevant disease experimental group there occurs significant change,
And Normal group is without significant change.
Quickly detected for malignant tumour and cardiovascular and cerebrovascular relevant disease early stage present invention also offers one kind and multi-modal
The image preparation of imaging, is synthesized by the metal ion reagent in lesions position by biology in situ effect fixed point.
For malignant tumour, the lesions position is liver cancer, lung cancer, cervical carcinoma, leukaemia, osteosarcoma, brain tumor or white
The lesions position of blood disease；For cardiovascular and cerebrovascular relevant disease, the lesions position is cerebral apoplexy or the lesion of senile dementia
Position.
The present invention provides described for malignant tumour and the quick detection of cardiovascular and cerebrovascular relevant disease early stage and multi-modal
Application of the metal ion reagent of imaging in malignant tumour and cardiovascular and cerebrovascular related disease target multi-modality imaging.With tumor model
Illustrate its applying step exemplified by mouse, when which is used for cancer target imaging, 0.05~0.2ml metal ions are tried
Agent is by the way that in tail vein injection or local injection to control group model mouse and tumor model mouse body, metal ion reagent can quickly exist
The lesions position enrichment of mouse and fabricated in situ image preparation, use small animal living body phosphorimager, CT imagers, ultrasonic imaging
Instrument and MRI are imaged model mouse, when imaging time window is 1~72 small.
Present invention also offers described to be used for malignant tumour and the quick detection of cardiovascular and cerebrovascular relevant disease early stage and multimode
Application of the metal ion reagent of state imaging in contrast agent is prepared.
The contrast agent is used in malignant tumour and the detection of cardiovascular and cerebrovascular relevant disease multi-modality imaging.
Compared with prior art, beneficial effects of the present invention are：
(1) metal ion reagent of the present invention, image preparation are using the excellent transition metal ions of biocompatibility, rare earth gold
Belong to ion and precious metal ion etc., be engaged with iron ion or ferrous ion, by being acted on target biology bioactive molecule fixed point
Realize that the accurate targeting mark of related lesions position is detected with fast imaging, the real-time dynamic high of live body non-intrusion type can be carried out
Sensitive quick tracer and monitoring.(2) metal ion reagent of the invention, image preparation inanimate object toxic side effect, detection method letter
Easy row, effectively prevent the chemical reagent introduced in Conventional nano material synthesis processes and nano material stabilizer to organic
Bio-toxicity caused by body, while avoid and be eliminated after Conventional nano material is easily captured by reticuloendothelial system so as to arrive
The shortcomings that up to lesion tissue, to realize that live body targeted imaging is analyzed.(3) metal ion reagent of the invention, image preparation can
In being detected applied to the multi-modality imaging of malignant tumour and cardiovascular and cerebrovascular relevant disease, imaging effect is good.The result shows that：Pass through
CT, MRI, fluorescence, ultrasound, optoacoustic and Raman spectrum (SERS) imaging etc. can quick recognition detection malignant tumour and cardiovascular and cerebrovasculars
Relevant disease site of pathological change is simultaneously enriched in the region, realizes the accurate mark of targeting lesions position.It these results suggest that the present invention
Metal ion reagent, image preparation can realize the early stage to cancer and cardiovascular and cerebrovascular relevant disease, quick, multi-modal (CT, surpass
Sound, fluorescence, optoacoustic and MRI etc.) image checking.The achievable not damaged of the present invention, original position, the malignant tumour of dynamic targeting in real time
It is imaged with cardiovascular and cerebrovascular relevant disease lesions position, carries out multiple dimensioned diagnosis synchronous with multi-modal and accurate targeting positioning with controlling
Treat, there is wide medical application prospect.
Brief description of the drawings
Fig. 1 is fluorescence imaging analysis result figure when cervical carcinoma model mouse time point is 24 small in embodiment 1；
Fig. 2 is MRI imaging analysis result figures when cervical carcinoma model mouse time point is 24 small in embodiment 1.
Embodiment
With reference to specific embodiment, the present invention is furture elucidated, it should be understood that these embodiments are merely to illustrate the present invention
Rather than limit the scope of the invention, after the present invention has been read, various equivalences of the those skilled in the art to the present invention
The modification of form falls within the application appended claims limited range.
Embodiment 1
1st, the preparation of metal ion reagent
The excellent metal ion reagent of biocompatibility is prepared, specific steps include：
Compound zinc chloride, europium sulfate are dissolved in ultra-pure water respectively, are configured to the solution that concentration is 10mmol/L；By chlorine
Change after zinc solution, the mixing of europium sulfate equal proportion again with the ferric chloride in aqueous solution (iron chloride is dissolved with ultra-pure water) of 10mmol/L according to
Volume 1:1 mixing, obtains metal ion reagent.
2nd, testing in vitro
Body fluid (such as blood or serum) or urine are tested using the metal ion reagent of the present embodiment, as a result
It has been shown that, the optics and electrochemical properties of tumor experiment group after the addition of metal ion reagent there occurs significant change, and just
Normal control group is without significant change.
Wherein, body fluid comes from normal person and leukaemia people, and urine comes from normal nude mice and tumor model nude mice.Tumour mould
Type nude mice is liver cancer (HepG2 cell lines) and cervical carcinoma (Hela cell lines), plants knurl mode and subcutaneously plants knurl for oxter.Optical detection
Method, which includes ultra-violet absorption spectrum measure and fluorescence spectrometry, electrochemical detection method, includes cyclic voltammetry and difference volt-ampere
Impulse method.
3rd, fluorescence imaging analysis
Fluorescence imaging analysis is carried out to tumor model mouse using the metal ion reagent of the present embodiment, specific steps include：
(1) the tumor model mouse of liver cancer (HepG2 cell lines) and the tumor model mouse of cervical carcinoma (Hela cell lines) are built,
Plant knurl mode and subcutaneously plant knurl for oxter.
(2) by metal ion reagent sterile 0.1mL, by tail vein and it is subcutaneously injected on tumor model mouse.
(3) it is imaged using living body fluorescent imager and is carried out qualitative and quantitative analysis to it.Specifically, utilize live body
Phosphorimager be imaged, respectively choose 1 it is small when, 4 it is small when, 8 it is small when, 12 it is small when, 24 it is small when, 48 it is small when etc. different time points, so
The experimental model mouse is subjected to gas anesthesia with 5% isoflurane afterwards, is placed on small animal living body imager operation platform, is selected
Select 420nm and 480nm wavelength excitation collection image.
The results show that the change for first increasing and weakening afterwards is presented with the time in the fluorescence intensity of the oxter tumor region of model mouse
Change, illustrate that image preparation with specific fabricated in situ or can be enriched in lesion region, be then gradually metabolized again.
4th, CT imaging analysis
CT imaging analysis are carried out to tumor model mouse using the metal ion reagent of the present embodiment, specific steps include：
(1) the tumor model mouse of liver cancer (HepG2 cell lines) and the tumor model mouse of cervical carcinoma (Hela cell lines) are built,
Plant knurl mode and subcutaneously plant knurl for oxter.
(2) by metal ion reagent sterile 0.1mL, by tail vein and it is subcutaneously injected on tumor model mouse.
(3) it is imaged using toy CT imagers and is carried out qualitative and quantitative analysis to it.Specifically, using CT into
As instrument be imaged, respectively choose 1 it is small when, 4 it is small when, 8 it is small when, 12 it is small when, 24 it is small when, 48 it is small when etc. different time points, then should
Experimental model mouse carries out gas anesthesia with 5% isoflurane, is placed on small animal living body CT imager operation platforms, selects naked
The oxter tumor region of mouse, gathers image.
The results show that the oxter tumor region of model mouse can significantly detect signal, different from the group of inside tumor
Knit density, it can be seen that granular high density material, illustrates that metal ion reagent is assembled in inside tumor targeting specific, and
And reduction becomes fluorescence and magnetic material (image preparation).
5th, MRI imaging analysis
MRI imaging analysis are carried out to tumor model mouse using the metal ion reagent of the present embodiment, specific steps include：
(1) the tumor model mouse of liver cancer (HepG2 cell lines) and the tumor model mouse of cervical carcinoma (Hela cell lines) are built,
Plant knurl mode and subcutaneously plant knurl for oxter.
(2) by metal ion reagent sterile 0.1mL, by tail vein and it is subcutaneously injected on tumor model mouse.
(3) it is imaged using toy MRI imagers and is carried out qualitative and quantitative analysis to it.Specifically, utilize MRI
(7.0T) imager be imaged, respectively choose 1 it is small when, 4 it is small when, 8 it is small when, 12 it is small when, 24 it is small when, 48 it is small when etc. different time points,
Then the experimental model mouse is subjected to gas anesthesia with 5% isoflurane, is placed on small animal living body MRI imager operation platforms
On, the lesion region of nude mice is selected, gathers image.
The results show that the oxter tumor region of model mouse can significantly detect signal, different from the group of inside tumor
Knit density, it can be seen that granular high density material, illustrates that metal ion reagent is assembled in inside tumor targeting specific, and
And reduction becomes fluorescence and magnetic material (image preparation).
Embodiment 2
1st, the preparation of metal ion reagent
The excellent metal ion reagent of biocompatibility is prepared, specific steps include：
Compound zinc gluconate is dissolved in ultra-pure water, is configured to the solution that concentration is 10mmol/L；By zinc gluconate
The ferrous chloride aqueous solution of solution and 10mmol/L are according to volume 1:3 mixing, obtain metal ion reagent.
2nd, testing in vitro
Body fluid (such as blood or serum) or urine are tested using metal ion reagent, the results show that tumour
The optics and electrochemical properties of experimental group after the addition of metal ion reagent there occurs significant change, and Normal group without
Significant change.
Wherein, body fluid comes from normal person and leukaemia people, and urine comes from normal nude mice and tumor model nude mice.Tumour mould
Type nude mice is liver cancer (HepG2 cell lines) and cervical carcinoma (Hela cell lines), plants knurl mode and subcutaneously plants knurl for oxter.Optical detection
Method, which includes ultra-violet absorption spectrum measure and fluorescence spectrometry, electrochemical detection method, includes cyclic voltammetry and difference volt-ampere
Impulse method.
3rd, fluorescence imaging analysis
Fluorescence imaging analysis, fluorescence imaging analysis side are carried out to tumor model mouse using the metal ion reagent of the present embodiment
Method is the same as embodiment 1.
The results show that the change for first increasing and weakening afterwards is presented with the time in tumor model mouse lesion region fluorescence intensity, say
Bright image preparation with specific fabricated in situ or can be enriched in lesion region, then gradually metabolism again.With in embodiment 1
Fluorescence intensity is compared, and the fluorescence intensity of the present embodiment has weakened.
4th, CT imaging analysis
CT imaging analysis are carried out to tumor model mouse using the metal ion reagent of the present embodiment, CT i mage analysis methods are same
Embodiment 1.
The results show that the lesion region of tumor model mouse can significantly detect signal, different from the group of inside tumor
Knit density, it can be seen that granular high density material, illustrates that metal ion reagent is assembled in inside tumor targeting specific, and
And reduction becomes fluorescence and magnetic material (image preparation).Compared with Example 1, the particle contrast in the present embodiment is more preferable, point
Cloth is more uniform.
5th, MRI imaging analysis
MRI imaging analysis, MRI i mage analysis methods are carried out to tumor model mouse using the metal ion reagent of the present embodiment
With embodiment 1.
The results show that the lesion region of tumor model mouse can significantly detect signal, different from the group of inside tumor
Knit density, it can be seen that granular high density material, illustrates that metal ion reagent is assembled in inside tumor targeting specific, and
And reduction becomes fluorescence and magnetic material (image preparation).Compared with Example 1, the particle contrast in the present embodiment is more preferable, point
Cloth is more uniform.
Embodiment 3
1st, the preparation of metal ion reagent
The excellent metal ion reagent of biocompatibility is prepared, specific steps include：
Compound gold chloride, silver nitrate are dissolved in ultra-pure water respectively, are configured to the solution that concentration is 10mmol/L；By chlorine
Auric acid solution, silver nitrate solution equal proportion mixing after again the ferric chloride in aqueous solution with 10mmol/L according to volume 1:2 mixing, obtain golden
Belong to Ion reagent.
2nd, testing in vitro
Body fluid (such as blood or serum) or urine are tested using metal ion reagent, the results show that tumour
The optics and electrochemical properties of experimental group after the addition of metal ion reagent there occurs significant change, and Normal group without
Significant change.
Wherein, body fluid comes from normal person and leukaemia people, and urine comes from normal nude mice and tumor model nude mice.Tumour mould
Type nude mice is liver cancer (HepG2 cell lines) and cervical carcinoma (Hela cell lines), plants knurl mode and subcutaneously plants knurl for oxter.Optical detection
Method, which includes ultra-violet absorption spectrum measure and fluorescence spectrometry, electrochemical detection method, includes cyclic voltammetry and difference volt-ampere
Impulse method.
3rd, fluorescence imaging analysis
Fluorescence imaging analysis, fluorescence imaging analysis side are carried out to tumor model mouse using the metal ion reagent of the present embodiment
Method is the same as embodiment 1.
The results show that the change for first increasing and weakening afterwards is presented with the time in tumor model mouse lesion region fluorescence intensity, say
Bright image preparation with specific fabricated in situ or can be enriched in lesion region, then gradually metabolism again.
4th, CT imaging analysis
CT imaging analysis are carried out to tumor model mouse using the metal ion reagent of the present embodiment, CT i mage analysis methods are same
Embodiment 1.
The results show that the lesion region of tumor model mouse can significantly detect signal, different from the group of inside tumor
Knit density, it can be seen that granular high density material, illustrates that metal ion reagent is assembled in inside tumor targeting specific, and
And reduction becomes fluorescence and magnetic material (image preparation).Compared with Example 1, the particle contrast in the present embodiment is more preferable, point
Cloth is more uniform.
5th, MRI imaging analysis
MRI imaging analysis, MRI i mage analysis methods are carried out to tumor model mouse using the metal ion reagent of the present embodiment
With embodiment 1.
The results show that the lesion region of tumor model mouse can significantly detect signal, different from the group of inside tumor
Knit density, it can be seen that granular high density material, illustrates that metal ion reagent is assembled in inside tumor targeting specific, and
And reduction becomes fluorescence and magnetic material (image preparation).
Embodiment 4
1st, the preparation of metal ion reagent
The excellent metal ion reagent of biocompatibility is prepared, specific steps include：
Compound europium nitrate is dissolved in ultra-pure water, is configured to the solution that concentration is 10mmol/L；By europium nitrate solution with
The ferrous chloride aqueous solution of 10mmol/L is according to volume 1:5 mixing, obtain metal ion reagent.
2nd, testing in vitro
Body fluid (such as blood or serum) or urine are tested using metal ion reagent, the results show that tumour
The optics and electrochemical properties of experimental group after the addition of metal ion reagent there occurs significant change, and Normal group without
Significant change.
Wherein, body fluid comes from normal person and leukaemia people, and urine comes from normal nude mice and tumor model nude mice.Tumour mould
Type nude mice is liver cancer (HepG2 cell lines) and cervical carcinoma (Hela cell lines), plants knurl mode and subcutaneously plants knurl for oxter.Optical detection
Method, which includes ultra-violet absorption spectrum measure and fluorescence spectrometry, electrochemical detection method, includes cyclic voltammetry and difference volt-ampere
Impulse method.
3rd, fluorescence imaging analysis
Fluorescence imaging analysis, fluorescence imaging analysis side are carried out to tumor model mouse using the metal ion reagent of the present embodiment
Method is the same as embodiment 1.
The results show that the change for first increasing and weakening afterwards is presented with the time in tumor model mouse lesion region fluorescence intensity, say
Bright image preparation with specific fabricated in situ or can be enriched in lesion region, then gradually metabolism again.
4th, CT imaging analysis
CT imaging analysis are carried out to tumor model mouse using the metal ion reagent of the present embodiment, CT i mage analysis methods are same
Embodiment 1.
The results show that the lesion region of tumor model mouse can significantly detect signal, different from the group of inside tumor
Knit density, it can be seen that granular high density material, illustrates that metal ion reagent is assembled in inside tumor targeting specific, and
And reduction becomes fluorescence and magnetic material (image preparation).
5th, MRI imaging analysis
MRI imaging analysis, MRI i mage analysis methods are carried out to tumor model mouse using the metal ion reagent of the present embodiment
With embodiment 1.
The results show that the lesion region of tumor model mouse can significantly detect signal, different from the group of inside tumor
Knit density, it can be seen that granular high density material, illustrates that metal ion reagent is assembled in inside tumor targeting specific, and
And reduction becomes fluorescence and magnetic material (image preparation).Compared with Example 1, the particle contrast in the present embodiment is more preferable, point
Cloth is more uniform.
Embodiment 5
1st, the preparation of metal ion reagent
The excellent metal ion reagent of biocompatibility is prepared, specific steps include：
Compound zinc chloride, gold chloride are dissolved in ultra-pure water respectively, are configured to the solution that concentration is 10mmol/L；By chlorine
Change the ferrous chloride aqueous solution after zinc, chlorauric acid solution mix in equal volume with 10mmol/L according to volume 1:4 mixing, obtain metal from
Sub- reagent.
2nd, testing in vitro
Body fluid (such as blood or serum) or urine are tested using metal ion reagent, the results show that tumour
The optics and electrochemical properties of experimental group after the addition of metal ion reagent there occurs significant change, and Normal group without
Significant change.
Wherein, body fluid comes from normal person and leukaemia people, and urine comes from normal nude mice and tumor model nude mice.Tumour mould
Type nude mice is liver cancer (HepG2 cell lines) and cervical carcinoma (Hela cell lines), plants knurl mode and subcutaneously plants knurl for oxter.Optical detection
Method, which includes ultra-violet absorption spectrum measure and fluorescence spectrometry, electrochemical detection method, includes cyclic voltammetry and difference volt-ampere
Impulse method.
3rd, fluorescence imaging analysis
Fluorescence imaging analysis, fluorescence imaging analysis side are carried out to tumor model mouse using the metal ion reagent of the present embodiment
Method is the same as embodiment 1.
The results show that the change for first increasing and weakening afterwards is presented with the time in tumor model mouse lesion region fluorescence intensity, say
Bright image preparation with specific fabricated in situ or can be enriched in lesion region, then gradually metabolism again.
4th, CT imaging analysis
CT imaging analysis are carried out to tumor model mouse using the metal ion reagent of the present embodiment, CT i mage analysis methods are same
Embodiment 1.
The results show that the lesion region of tumor model mouse can significantly detect signal, different from the group of inside tumor
Knit density, it can be seen that granular high density material, illustrates that metal ion reagent is assembled in inside tumor targeting specific, and
And reduction becomes fluorescence and magnetic material (image preparation).
5th, MRI imaging analysis
MRI imaging analysis, MRI i mage analysis methods are carried out to tumor model mouse using the metal ion reagent of the present embodiment
With embodiment 1.
The results show that the lesion region of tumor model mouse can significantly detect signal, different from the group of inside tumor
Knit density, it can be seen that granular high density material, illustrates that metal ion reagent is assembled in inside tumor targeting specific, and
And reduction becomes fluorescence and magnetic material (image preparation).Comparative example 1, the particle contrast in the present embodiment is more preferable, distribution
It is more uniform.
Embodiment 6
1st, the preparation of metal ion reagent
The excellent metal ion reagent of biocompatibility is prepared, specific steps include：
Compound zinc chloride, europium sulfate are dissolved in ultra-pure water respectively, are configured to the solution that concentration is 10mmol/L；By chlorine
Change zinc solution, europium sulfate equal proportion mixing after again the ferric chloride in aqueous solution with 10mmol/L according to volume 1:1 mixing, obtain metal from
Sub- reagent.
2nd, fluorescence imaging analysis
Fluorescence imaging analysis, specific steps bag are carried out to Senlie dementia model mouse using the metal ion reagent of the present embodiment
Include：
(1) the Senlie dementia model mouse of Different Month is built.
(2) by metal ion reagent sterile 0.1mL, by tail vein and it is subcutaneously injected on Senlie dementia model mouse.
(3) it is imaged using living body fluorescent imager and is carried out qualitative and quantitative analysis to it.Specifically, utilize live body
Phosphorimager be imaged, respectively choose 1 it is small when, 4 it is small when, 8 it is small when, 12 it is small when, 24 it is small when, 48 it is small when etc. different time points, so
The experimental model mouse is subjected to gas anesthesia with 5% isoflurane afterwards, is placed on small animal living body imager operation platform, is selected
Select 420nm and 480nm wavelength excitation collection image.
The results show that the fluorescence intensity of lesion region weakens afterwards as the time presents first to increase on senile dementia model mouse
Change, illustrate that the preparations such as the ion in reagent with specific fabricated in situ or can be enriched in lesion region, then again by
Gradually it is metabolized.At the same time fluorescence intensity show under the same terms, the senile dementia monthly age it is big model mouse enrichment more, fluorescence intensity
Bigger, illustrates doubling for lesion.
3rd, CT imaging analysis
CT imaging analysis, specific steps bag are carried out to senile dementia model mouse using the metal ion reagent of the present embodiment
Include：
(1) Senlie dementia model mouse is built.
(2) by metal ion reagent sterile 0.1mL, by tail vein and it is subcutaneously injected on Senlie dementia model mouse.
(3) it is imaged using toy CT imagers and is carried out qualitative and quantitative analysis to it.Specifically, using CT into
As instrument be imaged, respectively choose 1 it is small when, 4 it is small when, 8 it is small when, 12 it is small when, 24 it is small when, 48 it is small when etc. different time points, then should
Experimental model mouse carries out gas anesthesia with 5% isoflurane, is placed on small animal living body CT imager operation platforms, selects mould
The head zone of type mouse, gathers image.
The results show that the head zone of model mouse can significantly detect signal, can different from the tissue density on head
To see granular high density material, illustrate that metal ion reagent is assembled in intracerebral portion targeting specific, and and GAP-associated protein GAP
With reference to reduction becomes fluorescence and magnetic material (image preparation).
4th, MRI imaging analysis
MRI imaging analysis, specific steps bag are carried out to Senlie dementia model mouse using the metal ion reagent of the present embodiment
Include：
(1) Senlie dementia model mouse is built.
(2) by metal ion reagent sterile 0.1mL, by tail vein and it is subcutaneously injected on Senlie dementia model mouse.
(3) it is imaged using toy MRI imagers and is carried out qualitative and quantitative analysis to it.Specifically, utilize MRI
(7.0T) imager be imaged, respectively choose 1 it is small when, 4 it is small when, 8 it is small when, 12 it is small when, 24 it is small when, 48 it is small when etc. different time points,
Then the experimental model mouse is subjected to gas anesthesia with 5% isoflurane, is placed on small animal living body MRI imager operation platforms
On, the head zone of preference pattern mouse, gathers image.
The results show that the head zone of model mouse can significantly detect signal, can different from the tissue density on head
To see granular high density material, illustrate that metal ion reagent is assembled in intracerebral portion targeting specific, and and GAP-associated protein GAP
With reference to reduction becomes fluorescence and magnetic material (image preparation).
Embodiment 7
1st, the preparation of metal ion reagent
The excellent metal ion reagent of biocompatibility is prepared, specific steps include：
Compound zinc gluconate, gold chloride are dissolved in ultra-pure water respectively, are configured to the solution that concentration is 10mmol/L；
By zinc gluconate, gold chloride equal proportion mix after again the ferrous chloride aqueous solution with 10mmol/L according to volume 1:1 mixing, obtains
Metal ion reagent.
2nd, fluorescence imaging analysis
Fluorescence imaging analysis is carried out to stroke model mouse using the metal ion reagent of the present embodiment, specific steps include：
(1) structure cerebral apoplexy model mouse is induced using injury of blood vessel.
(2) by metal ion reagent sterile 0.1mL, by tail vein and it is subcutaneously injected on stroke model mouse.
(3) it is imaged using living body fluorescent imager and is carried out qualitative and quantitative analysis to it.Specifically, utilize live body
Phosphorimager be imaged, respectively choose 1 it is small when, 4 it is small when, 8 it is small when, 12 it is small when, 24 it is small when, 48 it is small when etc. different time points, so
The experimental model mouse is subjected to gas anesthesia with 5% isoflurane afterwards, is placed on small animal living body imager operation platform, is selected
Select 420nm and 480nm wavelength excitation collection image.
The results show that the change for first increasing and weakening afterwards is presented with the time in the fluorescence intensity of the upper lesion region of stroke model mouse
Change, illustrate that the preparations such as the ion in reagent with specific fabricated in situ or can be enriched in the lesion region of hypoxic-ischemic, and
Gradually metabolism again afterwards.
3rd, CT imaging analysis
CT imaging analysis are carried out to stroke model mouse using the metal ion reagent of the present embodiment, specific steps include：
(1) structure cerebral apoplexy model mouse is induced using injury of blood vessel.
(2) by metal ion reagent sterile 0.1mL, by tail vein and it is subcutaneously injected on stroke model mouse.
(3) it is imaged using toy CT imagers and is carried out qualitative and quantitative analysis to it.Specifically, using CT into
As instrument be imaged, respectively choose 1 it is small when, 4 it is small when, 8 it is small when, 12 it is small when, 24 it is small when, 48 it is small when etc. different time points, then should
Experimental model mouse carries out gas anesthesia with 5% isoflurane, is placed on small animal living body CT imager operation platforms, selects mould
The head zone of type mouse, gathers image.
The results show that the head injury region of model mouse can significantly detect signal, it is close different from the tissue on head
Degree, it can be seen that granular high density material, illustrates that damage field targeting specific of the metal ion reagent in intracerebral portion gathers
Collection, reduction become fluorescence and magnetic material (image preparation).
4th, MRI imaging analysis
MRI imaging analysis are carried out to stroke model mouse using the metal ion reagent of the present embodiment, specific steps include：
(1) structure cerebral apoplexy model mouse is induced using injury of blood vessel.
(2) by metal ion reagent sterile 0.1mL, by tail vein and it is subcutaneously injected into stroke model mouse.
(3) it is imaged using toy MRI imagers and is carried out qualitative and quantitative analysis to it.Specifically, utilize MRI
(7.0T) imager be imaged, respectively choose 1 it is small when, 4 it is small when, 8 it is small when, 12 it is small when, 24 it is small when, 48 it is small when etc. different time points,
Then the experimental model mouse is subjected to gas anesthesia with 5% isoflurane, is placed on small animal living body MRI imager operation platforms
On, the head zone of preference pattern mouse, gathers image.
The results show that the head zone of model mouse can significantly detect signal, can different from the tissue density on head
To see granular high density material, illustrate that damage field targeting specific of the metal ion reagent in intracerebral portion is assembled, also
Original becomes fluorescence and magnetic material (image preparation).
Comparative example 1
Compound iron chloride is dissolved in ultra-pure water, is configured to the solution that concentration is 10mmol/L, i.e. iron ion agent.
Fluorescence imaging analysis is carried out to tumor model mouse using the iron ion agent of the present embodiment, specific steps include：
(1) the tumor model mouse of liver cancer (HepG2 cell lines) and the tumor model mouse of cervical carcinoma (Hela cell lines) are built,
Plant knurl mode and subcutaneously plant knurl for oxter.
(2) by iron ion agent sterile 0.1mL, by tail vein and it is subcutaneously injected on tumor model mouse.
(3) it is imaged using living body fluorescent imager and is carried out qualitative and quantitative analysis to it.Specifically, utilize live body
Phosphorimager be imaged, respectively choose 1 it is small when, 4 it is small when, 8 it is small when, 12 it is small when, 24 it is small when, 48 it is small when etc. different time points, so
The experimental model mouse is subjected to gas anesthesia with 5% isoflurane afterwards, is placed on small animal living body imager operation platform, is selected
Select 420nm and 480nm wavelength excitation collection image.
Produced the results show that the oxter tumor region of model mouse is interior when 1~72 is small without obvious fluorescence signal, explanation
Single ferric chloride solution can not be applied to living body fluorescent and be imaged.
Claims (7)
- It is 1. a kind of for malignant tumour and the quick detection of cardiovascular and cerebrovascular relevant disease early stage and the metal ion examination of multi-modality imaging Agent, it is the aqueous solution containing metal ion, it is characterised in that the metal ion by iron ion or ferrous ion and magnesium from At least one of son, transition metal ions, rare earth ion and precious metal ion are formulated；Wherein, the transition Metal ion is the mixture of one or both of cerium ion, zinc ion；In metal ion reagent, iron ion or ferrous ion Molar ratio with other metal ions is 5~1:1.
- 2. metal ion reagent as claimed in claim 1, it is characterised in that the rare earth ion is europium ion, lanthanum The mixture of one or both of ion.
- 3. metal ion reagent as claimed in claim 1, it is characterised in that the precious metal ion for gold ion, silver from The mixture of one or both of son, platinum ion.
- 4. metal ion reagent as claimed in claim 1, it is characterised in that in metal ion reagent, iron ion or it is ferrous from The concentration of son is 5~10mmol/L.
- 5. a kind of be used for malignant tumour and the image preparation of the quick detection of cardiovascular and cerebrovascular relevant disease early stage and multi-modality imaging, its It is characterized in that, is acted on and determined by biology in situ in lesions position by such as Claims 1 to 4 any one of them metal ion reagent Point synthesis.
- 6. it is used for malignant tumour and the quick detection of cardiovascular and cerebrovascular relevant disease early stage and multi-modality imaging as claimed in claim 5 Image preparation, it is characterised in that lesion is derived from liver cancer, lung cancer, cervical carcinoma, osteosarcoma, brain tumor, leukaemia, cerebral apoplexy or old Dementia disease.
- 7. as Claims 1 to 4 any one of them be used for malignant tumour and the quick detection of cardiovascular and cerebrovascular relevant disease early stage and Application of the metal ion reagent of multi-modality imaging in contrast agent is prepared.
Priority Applications (2)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| CN201510667003.5A CN105214103B (en) | 2015-10-14 | 2015-10-14 | For malignant tumour and the metal ion reagent and image preparation of the quick detection of cardiovascular and cerebrovascular relevant disease early stage and multi-modality imaging |
| PCT/CN2015/096309 WO2017063258A1 (en) | 2015-10-14 | 2015-12-03 | Metallic ion reagent used for early rapid detection and multi-mode imaging of diseases related to malignant tumor and cardiovascular disease, and imaging preparation |
Applications Claiming Priority (1)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| CN201510667003.5A CN105214103B (en) | 2015-10-14 | 2015-10-14 | For malignant tumour and the metal ion reagent and image preparation of the quick detection of cardiovascular and cerebrovascular relevant disease early stage and multi-modality imaging |
Publications (2)
| Publication Number | Publication Date |
|---|---|
| CN105214103A CN105214103A (en) | 2016-01-06 |
| CN105214103B true CN105214103B (en) | 2018-04-24 |
Family
ID=54983608
Family Applications (1)
| Application Number | Title | Priority Date | Filing Date |
|---|---|---|---|
| CN201510667003.5A Active CN105214103B (en) | 2015-10-14 | 2015-10-14 | For malignant tumour and the metal ion reagent and image preparation of the quick detection of cardiovascular and cerebrovascular relevant disease early stage and multi-modality imaging |
Country Status (2)
| Country | Link |
|---|---|
| CN (1) | CN105214103B (en) |
| WO (1) | WO2017063258A1 (en) |
Families Citing this family (1)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| CN114468997A (en) * | 2022-01-18 | 2022-05-13 | 中国科学院精密测量科学与技术创新研究院 | Multi-mode detection method for in-situ transplantation lung cancer model |
Citations (4)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| CN103083687A (en) * | 2013-01-16 | 2013-05-08 | 东南大学 | Application of silver and platinum nano-cluster in tumor targeted imaging |
| CN103143037A (en) * | 2013-03-01 | 2013-06-12 | 东南大学 | Method for synthesizing rare earth metal compound nano cluster and application thereof |
| CN103330948A (en) * | 2013-07-05 | 2013-10-02 | 东南大学 | Tumor targeted living body rapid fluorescence imaging method of rare earth metal nanocluster |
| CN104587493A (en) * | 2015-02-05 | 2015-05-06 | 东南大学 | Detection reagents for fast and real-time dynamic monitoring and multimode imaging in early stage of cardio-cerebrovascular related diseases |
Family Cites Families (2)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| CN103099604B (en) * | 2013-01-15 | 2015-05-06 | 东南大学 | An imaging method of tumor targeting based on enhancement effect of zinc ion signals |
| CN103212056B (en) * | 2013-05-07 | 2015-07-08 | 东南大学 | Preparation based on gold, silver, gold-silver mixture and glutathione/chitosan, and application of preparation |
-
2015
- 2015-10-14 CN CN201510667003.5A patent/CN105214103B/en active Active
- 2015-12-03 WO PCT/CN2015/096309 patent/WO2017063258A1/en active Application Filing
Patent Citations (4)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| CN103083687A (en) * | 2013-01-16 | 2013-05-08 | 东南大学 | Application of silver and platinum nano-cluster in tumor targeted imaging |
| CN103143037A (en) * | 2013-03-01 | 2013-06-12 | 东南大学 | Method for synthesizing rare earth metal compound nano cluster and application thereof |
| CN103330948A (en) * | 2013-07-05 | 2013-10-02 | 东南大学 | Tumor targeted living body rapid fluorescence imaging method of rare earth metal nanocluster |
| CN104587493A (en) * | 2015-02-05 | 2015-05-06 | 东南大学 | Detection reagents for fast and real-time dynamic monitoring and multimode imaging in early stage of cardio-cerebrovascular related diseases |
Non-Patent Citations (1)
| Title |
|---|
| "In vivo accurate target bio-marking of tumors through in situ biosynthesized fluorescent zinc nanoclusters";Meina Su等;《RSC Advances》;20150824;第5卷;第74844-74849页 * |
Also Published As
| Publication number | Publication date |
|---|---|
| WO2017063258A1 (en) | 2017-04-20 |
| CN105214103A (en) | 2016-01-06 |
Similar Documents
| Publication | Publication Date | Title |
|---|---|---|
| US9724431B2 (en) | Tumor-targeting multi-mode imaging method for living body based on gold nanoclusters | |
| Morgan et al. | Real time in vivo non-invasive optical imaging using near-infrared fluorescent quantum dots1 | |
| US10712277B2 (en) | Raman imaging devices and methods of molecular imaging | |
| McConnell et al. | Ferumoxytol nanoparticle uptake in brain during acute neuroinflammation is cell-specific | |
| CN102743770B (en) | A kind of targeting molecule image probe and living body molecule imaging method | |
| CN103330948B (en) | Tumor targeted living body rapid fluorescence imaging method of rare earth metal nanocluster | |
| Akshulakov et al. | Current trends for improving safety of stereotactic brain biopsies: advanced optical methods for vessel avoidance and tumor detection | |
| EP2940474A1 (en) | Novel labeling composition for cancer lesion | |
| Chen et al. | Tracking the in vivo spatio-temporal patterns of neovascularization via NIR-II fluorescence imaging | |
| CN106075469A (en) | Gd3+induction gold nano cluster is self-assembled into method and the application of gold nano grain | |
| Yu et al. | Multifunctional gold nanoparticles as smart nanovehicles with enhanced tumour-targeting abilities for intracellular pH mapping and in vivo MR/fluorescence imaging | |
| CN109395101A (en) | Target the preparation method of the mr contrast agent of blood-brain barrier and glioma | |
| Jia et al. | Precise visual distinction of brain glioma from normal tissues via targeted photoacoustic and fluorescence navigation | |
| Subasinghe et al. | Dual-mode tumor imaging using probes that are responsive to hypoxia-induced pathological conditions | |
| CN104225630B (en) | Multi-mode self-assembly nanoprobe suitable for MRI (magnetic resonance imaging)/PA (optical activation) and other imaging | |
| Yu et al. | An NIR Fluorescence Turn‐on and MRl Bimodal Probe for Concurrent Real‐time in vivo Sensing and Labeling of β‐Galactosidase | |
| Yang et al. | Near-infrared-II bioimaging for in vivo quantitative analysis | |
| Dong et al. | A natural cuttlefish melanin nanoprobe for preoperative and intraoperative mapping of lymph nodes | |
| Virani et al. | In vivo hypoxia characterization using blood oxygen level dependent magnetic resonance imaging in a preclinical glioblastoma mouse model | |
| CN105214103B (en) | For malignant tumour and the metal ion reagent and image preparation of the quick detection of cardiovascular and cerebrovascular relevant disease early stage and multi-modality imaging | |
| CN102665536B (en) | The method of biological liver performance is determined in metabolism by means of quantitative measurement substrate | |
| CN115389544B (en) | Method and application for measuring water molecule outflow rate across cell membrane, and method and system for measuring glioma magnetic resonance imaging marker | |
| CN114231272B (en) | Near infrared II region nano probe for liver imaging and preparation and application thereof | |
| CN104689344B (en) | It is applied to the early stage quick detection of senile dementia and its image preparation of multi-modality imaging | |
| Ripoll et al. | Investigating pharmacology in vivo using magnetic resonance and optical imaging |
Legal Events
| Date | Code | Title | Description |
|---|---|---|---|
| C06 | Publication | ||
| PB01 | Publication | ||
| C10 | Entry into substantive examination | ||
| SE01 | Entry into force of request for substantive examination | ||
| GR01 | Patent grant | ||
| GR01 | Patent grant |