CN104117075B - Gold nanorod multifunctional probe-based nuclide-cerenkov luminescence-CT multi-mode imaging method - Google Patents
Gold nanorod multifunctional probe-based nuclide-cerenkov luminescence-CT multi-mode imaging method Download PDFInfo
- Publication number
- CN104117075B CN104117075B CN201410370072.5A CN201410370072A CN104117075B CN 104117075 B CN104117075 B CN 104117075B CN 201410370072 A CN201410370072 A CN 201410370072A CN 104117075 B CN104117075 B CN 104117075B
- Authority
- CN
- China
- Prior art keywords
- rgd
- aunrs
- probe
- imaging
- polyfunctional molecule
- 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 - Fee Related
Links
Landscapes
- Medicines Containing Antibodies Or Antigens For Use As Internal Diagnostic Agents (AREA)
Abstract
The invention discloses a gold nanorod multifunctional probe-based nuclide-cerenkov luminescence-CT multi-mode imaging method, which applies a ＜68＞Ga-AuNRs-RGD multifunctional molecular probe to the field of multi-mode molecular imaging. The caudal vein of a tumor-bearing mouse is injected with the ＜68＞Ga-AuNRs-RGD multifunctional molecular probe, nuclide-CT imaging is performed by a PET/CT imaging system, cerenkov luminescence-CT imaging is performed by a CLI/CT (cerenkov luminescence imaging/computed tomography) system, and a PET/CT image serving as a source image and a CLI/CT image serving as a target image are fused by means of grey rectification to obtain a nuclide-cerenkov luminescence-CT multi-mode imaging display image based on the ＜68＞Ga-AuNRs-RGD multifunctional molecular probe. According to the method, the ＜68＞Ga-AuNRs-RGD multifunctional molecular probe is applied to multi-mode molecular imaging, has the advantages of increasing optical signal intensity, improving imaging resolution, improving imaging depth and the like, and has the characteristics of excellent dispersion, low toxicity, high living cell membrane permeability and the like.
Description
Technical field
The present invention relates to biomedical imaging field and in particular to a kind of nucleic based on gold nanorods multiprobe-
Cherenkov lights-ct multi-modality imaging method.
Background technology
The development of nanotechnology promotes a collection of birth with the property nano material such as unique light, electricity, magnetic, and they extensively should
For in the diagnosis and Therapy study of tumor.Noble metal nanometer material, especially gold nano grain, its adjustable for height optics is special
Property can greatly enhance the absorption to visible ray and near infrared light, and its good optical property and surface chemistry ability can be to tumors
Tissue carries out being accurately positioned and efficiently treats, and is expected to become the new tool of cancer clinical treatment.
At present, the gold nano grain in imaging field application mostly is that size uniformity, colloidal stability be good, the gold less than 50nm
Nano-particle, these nano-particle are spherical in shape, shell dress, bar-shaped, caged are in terms of the different kinds of molecules imaging techniques such as ct acoustooptics mri
With.Gold nano grain can extend the time of staying in blood circulation effectively, not only extends time of developing, it is extremely low
Cytotoxicity also reduce the toxic and side effects to kidney.The easily-controllable surface chemistry affinity of gold nano grain can be with some
Specific antibody protein couples, and prepares the nano-probe of functionalization.Have any different in ordinary cells in malignant cell surface
Overexpression receptor, can specifically bind the gold nano-material with corresponding protein molecular.Integrin alphavβ3In kinds of tumor cells table
High expression on face and neovascular endothelium cell, but α in ripe vascular endothelial cell and most normal organ systemvβ3
Do not express or minimal amount of expression.Rgd polypeptide is that a class contains arginine-glycine-aspartic acid (arg-gly-asp)
Small peptide, by αvβ3As the binding site of tumor, by rgd and αvβ3Specific binding so that gold nanorods and tumor cell
Specific binding.Gold nanorods (gold nanorods, aunrs) are combined with rgd so that gold nanorods can be selectively targeted
Tumor cell.In tumor locus, gold nano-material can attenuated x-rays well, carry out ct imaging as ct contrast agent, obtain
The ct image of tumor locus.
Gold nano optical imagery is very limited in viviperception and clinical conversion, a lot of research teams attempt by
Other imaging molecule probes, such as nucleic probe64Cu and111In, optical probe icg, magnetic resonance probe fe3o4Deng labelling gold nano
Material construction multifunctional nano probe, carries out living imaging and the Therapy study of gold nano target tumor.Radio nuclide imaging is applied
The details of focus can be obtained in oncotherapy.But radio nuclide imaging, as pet, spect image sensitivity height, is not subject to
The restriction of investigation depth, but its apparatus expensive, spatial resolution is low.At present, grind in the diagnosis of gold nano target tumor and treatment
In studying carefully, joint radio nuclide imaging and optical image technology develop multifunctional nano probe, are implemented as picture and treatment integration, in future
Biomedical research in have great significance.Cerenkov effect is found in 1934 by scientist cerenkov, refers to carry
One part energy can be converted into the visible ray of 400-900nm wave band and closely red when charged particle is run in media as well with superlight speed
Outer light.Radioisotopic Cherenkov's luminescence imaging (cerenkov luminescence imaging, cli) is to utilize
The imaging that the light that nucleic Cerenkov effect produces is carried out.Cherenkov's luminescence imaging has the advantages that many optical imageries, than
As high in sensitivity, cheap, imaging time is short, be easy to carry out etc..More importantly it is based on Cerenkov effect, for same
Isotope labeling molecular probe can carry out optical imagery with radio nuclide imaging respectively hence it is evident that being different from traditional multiple labelling molecular probe
The multi-modality imaging carrying out is it is easier to keep the biological activity of molecular probe, and the vivo biodistribution based on same molecular probe
Process carries out optics and radio nuclide imaging respectively, is conducive to carrying out image co-registration research.The height being produced due to multiple radionuclides
Cerenkov effect occurrence condition can be satisfied by by charged particle, can produce and can be collected by high-sensitive optical imaging apparatus
Optical signalling, therefore can be utilized existing isotope labeling molecular probe to carry out clinical optics imaging, can overcome optical dye poison
Property larger be difficult to use in clinic deficiency.
Single image mode cannot provide sufficiently comprehensive information for medical diagnosis on disease.In order to realize the early stage to major disease
Diagnosis and accurate treatment, in conjunction with different imaging patterns advantage obtain sensitiveer, more accurately, more fully physiological and pathological information
Multi-mode molecule imaging becomes focus and the development trend of molecular image development.Ct, nucleic, Cherenkov are imaged the many of combination
Modality, can mutually make up the inferior position of respective imaging, and obtain tumor using the advantage of respective imaging between each mode
The details at position, provide more comprehensive and detailed information for diagnosing and treating.
Content of the invention
For the deficiencies in the prior art, the purpose of the present invention is by a kind of special gold nanorods multiprobe, profit
With probe, multi-modality imaging is carried out to animal model for tumour.First with rgd to tumor vascular targeting, multiprobe is special
The opposite sex is gathered in tumor locus, and gold nanorods carry out ct imaging as ct contrast agent, then passes through radionuclide68Ga carries out core
Element imaging and Cherenkov's luminescence imaging.
For above-mentioned purpose, the present invention adopts the following technical scheme that
Step 1, the preparation of gold nanorods polyfunctional molecule probe:
Step 1.1, prepares gold nanorods (aunrs)
By cetyl trimethylammonium bromide (ctab) and gold chloride mixing, add sodium borohydride, then quickly stir, obtain
To crystal seed；Then gained crystal seed, standing are added in the seeded growth liquid containing silver nitrate, gold chloride, ctab and ascorbic acid
The gold nanorods of specific draw ratio are obtained afterwards；
Step 1.2, preparation68Ga-aunrs-rgd polyfunctional molecule probe
Small-molecular peptides and radiosiotope using arginine-glycine-aspartic acid (rgd) tripeptide sequence68Ga comes
Labelling gold nanorods.
First by difunctional Polyethylene Glycol (opps-peg2k-nhs) bridging agent of excessive different molecular weight respectively with essence
Propylhomoserin-Gly-Asp (rgd) and Isosorbide-5-Nitrae, 7,10- tetraazacyclododecanands-Isosorbide-5-Nitrae, 7,10- tetrabasic carboxylic acids (dota) mix,
Under room temperature overnight, form stable bridging agent opps-peg-rgd and opps-peg-dota.Then by two kinds of bridging agents and Jenner
With the ratio mixing of 2500:2500:1, by the combination of adjacent two thiopyridines bases (opss), rgd and dota is stably connected with rice rod
Gold nanorods surface.Finally, radiotropism isotope in certain proportion68The Jenner that rgd and dota is stably connected with is added in ga
The excellent coalition of rice, mixes, reacts 20 minutes, be obtained68Ga-aunrs-rgd polyfunctional molecule probe.
It should be noted that step 1.268Difunctional in the preparation process of ga-aunrs-rgd polyfunctional molecule probe
The molecular weight of Polyethylene Glycol (opps-peg-nhs) bridging agent is different, and the opps-peg-nhs molecular weight being connected with rgd is 2000,
The opps-peg-nhs molecular weight being connected with dota is 5000.
Step 2,68The performance detection of ga-aunrs-rgd polyfunctional molecule probe:
Step 2.1,68Ga-aunrs-rgd polyfunctional molecule probe steady is tested
Using the detection of 10%nacl solution68Ga-aunrs-rgd polyfunctional molecule probe steady.By same concentrations68Ga-aunrs-rgd polyfunctional molecule probe and gold nanorods are resuspended in 10% nacl solution of equivalent respectively, Ran Houjin
Row uvs spectral detection, compares both stability differences.
Step 2.2,68Ga-aunrs-rgd polyfunctional molecule fluorescence probe quantum efficiency and extracorporeal receptor binding analysis
First, measure68Cherenkov's photo-quantum efficiency of ga-aunrs-rgd polyfunctional molecule probe: relatively more different68ga
Same concentration under radioactivity68Cherenkov's signal photo-quantum efficiency of ga-aunrs-rgd polyfunctional molecule probe, optimizes
Test parameterss, obtain luminous efficiency optimized Fluorescence Increasing type68Ga-aunrs-rgd polyfunctional molecule probe；
Secondly, measure68The biology performance of ga-aunrs-rgd polyfunctional molecule probe: adopt68The aunrs- of ga labelling
As radioligand, unlabelled aunrs-rgd molecular probe is non-tagged ligand to rgd molecular probe, and analysis is to αvβ3Receptor
The positive glioma u87 cell of expression carries out receptor ligand binding assay.Two kinds of parts are combined with suspension cell, detect them
Radioactive dosage and luminous efficiency.
Step 3, tumor bearing nude mice Animal Model:
Choose glioma cell u87, cultured cell in vitro, at the right shoulder of nude mice subcutaneous injection of tumor cells several, structure
Build subcutaneous tumor model, after 2-3 week, carry out multi-modality imaging detection；
It should be noted that after 2-3 week, tumor model is with diameter greater than carrying out multi-modality imaging detection again after 0.5cm.
Step 4,68The multi-modality imaging of ga-aunrs-rgd polyfunctional molecule probe:
Step 4.1, pet/ct image data acquiring
Pet/ct data acquisition, mouse tail vein injection are carried out to tumor bearing nude mice using pet/ct system68ga-aunrs-
Carry out pet/ct scanning in different time points after rgd polyfunctional molecule probe, obtain the nucleic-ct image of different time points
Data；
Step 4.2, cli/ct image data acquiring
Cli/ct data acquisition, mouse tail vein injection are carried out to described tumor bearing nude mice using cli/ct imaging system68ga-
Obtain multiple spectrum under airtight dark situation, multiple regard in different time points after aunrs-rgd polyfunctional molecule probe
Cherenkov's luminous signal of angle petty action object table and ct view data.
Step 4.3, pet/ct and cli/ct fusing image data
As target image, the pet/ct that step 4.1 draws, as source images, passes through the cli/ct that step 4.2 is drawn
The pretreatment such as image denoising, enhancing, image segmentation carries out feature extraction, mutual information image registration, the image based on image pixel
Merge, just obtain68The nucleic of tumor region of ga-aunrs-rgd polyfunctional molecule probe targeting, Cherenkov light, ct
Multi-modality imaging imaging figure.
It should be noted that in step 4, the α of the rgd target tumor blood vessel on gold nanorods surfacevβ3Receptor, to tumor
Specifically bound.
It should be noted that in step 4, based on gold nanorods surface same molecular probe radionuclide68The body of ga
Interior bioprocess carries out optics and radio nuclide imaging respectively, is conducive to carrying out image co-registration research.
The present invention adopts68Ga-aunrs-rgd molecular probe, tumor bearing nude mice is carried out ct, nucleic, Cherenkov light many
Modality has a beneficial effect as is evident below:
1. adopt gold nanorods to replace the contrast agent that iodide are imaged as ct, can significantly increase imaging time, no
Toxic and side effects, greatly reduce the dosage of x-ray, and improve spatial resolution；
2. adopt rgd target tumor to organize, by the integrin alpha in rgd and tumor neogenetic blood vesselsvβ3Specific binding,
Tail vein injection 68ga-aunrs-rgd molecular probe is enable preferably to be gathered in tumor locus；
3. nucleic and Cherenkov's luminescence imaging are completed using a kind of radioelement labelling gold nano molecular probe；
4. adopt the luminous-ct multi-modality imaging of nucleic-Cherenkov, nucleic and Cherenkov's luminescence imaging to tumor locus
Carry out functional imaging, improve imaging depth, ct obtains three bit distribution information in mice body for the tumor.
Brief description
Fig. 1 is flow chart of the present invention；
Fig. 2 is the transmission electron microscope picture of gold nanorods；
Fig. 3 be gold nanorods and68The UV-vis spectroscopy degree meter testing result of ga-aunrs-rgd polyfunctional molecule probe
Figure；
Fig. 4 is68Ga-aunrs-rgd polyfunctional molecule probe and the Detection of Stability result figure of gold nanorods.
Specific embodiment
Below with reference to accompanying drawing, the invention will be further described, it should be noted that the present embodiment is with this technology side
Premised on case, provide detailed embodiment and implementation steps, but be not limited to the present embodiment.
- ct multi-modality imaging the side as shown in figure 1, described nucleic-Cherenkov based on gold nanorods multiprobe lights
Method comprises the steps:
The preparation of gold nanorods (aunrs):
When temperature is for 27-30 DEG C, to 5ml, add 5ml, the gold chloride of 0.5mm in the ctab of 0.2m, be slowly stirred, this
When solution be faint yellow.Then slow, it is added dropwise over 0.6ml, the sodium borohydride of 0.01m freezing point, quickly stir 2min, now molten
Liquid have light yellow be changed into light brown, eventually become claret, crystal seed generates.Preserve at 30 DEG C, in case follow-up test.
In the case of lucifuge, to 5ml, in the ctab of 0.2m, add 0.25ml, the silver nitrate solution of 4mm, be then followed by adding
Enter 5ml, the gold chloride of 1mm, now solution is yellow, adds 70ul, the ascorbic acid of 0.0788m afterwards, is eventually adding 12ul
Gained crystal seed, lucifuge at 30 DEG C, stand 3h, obtain the more uniform gold nanorods of granule, the transmission electron microscope picture of gold nanorods
As shown in Figure 2.
68The preparation of ga-aunrs-rgd polyfunctional molecule probe:
Rgd the and dota solution of 500ul (1mg/ml) prepared by pbs buffer (ph=7.4), then respectively to rgd and
8.82 × 10 are added in dota solution-2Edc and nhs of mmol, activates the carboxyl of rgd and dota, room temperature by amidation process
It is separately added into 30mg opps-peg-nhs (mw=2k) and opps- in the backward rgd solution of lower reaction 30min and dota solution
Peg-nhs (mw=5k), finally reacts 6h at 4 DEG C, and the carboxyl after activation is combined with the amino of double-functional group and generates two kinds
Bridging agent opps-peg-rgd and opps-peg-dota.Then each for two kinds of bridging agents 500ul is added to 2ml, 300ug/ml's
In gold nanorods solution, moderate-speed mixer, reacts 24h at 25 DEG C, by opps, rgd and dota is stably connected with gold nanorods
Surface, is then centrifuged 10min, removes unnecessary unreacted bridging agent, precipitation is resuspended to the deionized water of 1ml under 11000r
In, obtain rgd targeting gold nanorods.
Using68Ga radionuclide is marked gold nanorods, to carry out nucleic and Cherenkov's luminescence imaging, first
Rgd and dota is stably connected with gold nanorods and is adjusted to 3.5-4.0 with reference to the ph value of liquid solution, be subsequently adding68Ga, both are with 100:
1 ratio mixes, and 90 DEG C of lucifuges are reacted 20 minutes.The chelating agen dota on gold nanorods surface is used for label isotope68Ga, changes
The molecular weight of Polyethylene Glycol (peg), can control68Ga couples distance with gold nanorods surface, obtains68ga-aunrs-rgd
Polyfunctional molecule probe.In preparation process, the UV, visible light spectrophotometer testing result of each step products is as shown in Figure 3.
68The stability test of ga-aunrs-rgd molecular probe:
Test the monodispersity of gold nanorods material using high level salt solution, take concentration to be all 600ug/ml's68ga-aunrs-
The each 100ul of rgd and aunrs solution, is resuspended in the 10% nacl solution of 1ml respectively, and two kinds of mixed solutions stand at 4 DEG C
24h, then carries out wave spectrum detection using UV-vis spectroscopy degree meter, as shown in figure 4, the wave spectrum obtaining with68ga-aunrs-rgd
It is compared with the aqueous solution wave spectrum of aunrs, obtain68The stability test result of ga-aunrs-rgd molecular probe.
68Ga-aunrs-rgd polyfunctional molecule fluorescence quantum efficiency and extracorporeal receptor binding analysis:
First, measure68Cherenkov's photo-quantum efficiency of ga-aunrs-rgd polyfunctional molecule probe: using pet system
Collection is different68Under ga radioactivity68The nucleic signal of ga-aunrs-rgd molecular probe, selects sense emerging on nuclide chart picture
Interesting region, can obtain light using living image3.2 software (ivis kinetic, caliper life sciences)
Learn the intensity of signal.This patent finds Cherenkov's optics signal and radioactivity linear correlation.Optimization Test parameter, obtains
Luminous efficiency optimized Fluorescence Increasing type68Ga-aunrs-rgd polyfunctional molecule probe.Secondly, measure68ga-aunrs-rgd
The biology performance of polyfunctional molecule probe: using to αvβ3The positive glioma u87 cell of expression of receptor carries out receptors ligand knot
Close test.Prepare number of cells identical u87 cell suspending liquid and be labeled as each 1ml of a, b group, then take au concentration to be 600ug/ml
Aunrs and68Ga-aunrs-rgd solution (filtration sterilization) cell culture medium is 0.1nm to au concentration, respectively takes
100ul, is added separately in a, b group cell suspending liquid, cultivates 30 minutes in cell culture incubator.A, b group cell suspending liquid is entered
Row nucleic and Cherenkov's luminescence imaging, detect their radioactive dosage and luminous efficiency.
Pet/ct image data acquiring:
Using nanoscan pet/ct, mediso, medical imaging systems system is carried out to tumor bearing nude mice
Pet/ct image data acquiring, this system is detected by the pet detector of a pair of Relative vertical, x-ray emission device, x-ray flat board
Device, toy support and rotation translation stage are constituted, and set image acquisition voltage as 55kv, and collection electric current is 146ua, image acquisition
Angle is 240.To tumor-bearing mice tail vein injection 100ul, concentration is 4mg/ml's68Ga-aunrs-rgd polyfunctional molecule probe
Afterwards, respectively at 1,3,6,12,24h carry out pet imaging, observe radiopharmaceutical distribution in vivo, metabolism and in tumor uptake
Dynamic change.Carry out ct scanning simultaneously, for image registration, merge offer details.
Cli/ct image data acquiring:
Cli/ct image data acquiring is carried out to tumor bearing nude mice using bimodal zkks-direct3d molecular imaging system,
This system is made up of Cherenkov's luminescence imaging system and micro-ct system.Cherenkov's luminescence imaging system is by high sensitivity
Refrigeration ccd detector, scan-type spectrometer device, filter lens group composition.Micro-ct system is penetrated by x-ray emission device, x
Line flat panel detector, toy support and rotation translation stage constitute composition.Set image acquisition voltage as 50kv, collection electric current is
10ma, 360 ° of image acquisition.To tumor-bearing mice tail vein injection 100ul, concentration is 4mg/ml's68Ga-aunrs-rgd is multi-functional
Under completely airtight dark situation, after molecular probe, place the band pass filter of one group of different-waveband before highly sensitive refrigeration ccd,
Multiple visual angles detect Cherenkov's luminous signal of petty action object table, obtain the white light figure with stent markers point information simultaneously
Picture, so that the influence of noise such as DC-offset correction.Using spectrometer device, body surface luminous signal is swept on certain wave band
Retouch detection, obtain the spectral distribution of this wave band luminous signal.Carry out ct scanning simultaneously, obtain three information of tumor locus, for figure
As registration, merge offer details.
Pet/ct and cli/ct image co-registration:
The two kinds of view data of pet/ct and cli/ct obtaining are carried out with denoising, the pretreatment such as enhancing.Unified two kinds of data
Form, the image parameter such as image size and resolution.Using mouse tumor region as area-of-interest, select specific segmentation threshold
Value carries out manual segmentation to image, draws the geometric properties of image, then optimizes the phase of two kinds of images of pet/ct and cli/ct
Like property using pet/ct as source images, cli/ct as target image, by source images the gray scale registration based on mutual information and mesh
Logo image carries out registration, obtains the transformation relation of two width images, then applies transformation relation on pet image.Finally by two
Width pet/ct and cli/ct image are merged based on image pixel, have obtained pet/cli/ct tri- modality images information, have carried out
Imaging, that is, obtain68The multi-modality imaging of the animal model for tumour of ga-aunrs-rgd labelling.
For a person skilled in the art, can make various corresponding according to above technical scheme and design
Deformation and change, and all these changes and deformation should be construed as being included within the protection domain of the claims in the present invention.
Claims (5)
1. a kind of for nucleic-Cherenkov light-ct multi-modality imaging probe preparation method it is characterised in that described side
Method comprises the steps:
Step 1, the preparation of gold nanorods polyfunctional molecule probe
Step 1.1, prepares gold nanorods (aunrs):
By cetyl trimethylammonium bromide (ctab) and gold chloride mixing, add sodium borohydride, quick stirring, obtain crystal seed；
Then add gained crystal seed in the seeded growth liquid containing silver nitrate, gold chloride, ctab and ascorbic acid, standing obtains specific
The gold nanorods of draw ratio；
Step 1.2, preparation68Ga-aunrs-rgd polyfunctional molecule probe:
Small-molecular peptides and radiosiotope using arginine-glycine-aspartic acid (rgd) tripeptide sequence68Ga carrys out labelling
Gold nanorods；
First by difunctional Polyethylene Glycol (opps-peg-nhs) bridging agent of excessive difference mean molecule quantities respectively with smart ammonia
Acid-Gly-Asp (rgd) and Isosorbide-5-Nitrae, 7,10- tetraazacyclododecanands-Isosorbide-5-Nitrae, 7,10- tetrabasic carboxylic acids (dota) mix, room
Under temperature overnight, form stable bridging agent opps-peg-rgd and opps-peg-dota；Then by two kinds of bridging agent opps-
Peg-rgd and opps-peg-dota and described gold nanorods are mixed with the ratio of mol ratio 2500:2500:1, by adjacent two sulfur
The combination of pyridine radicals (opss), rgd and dota is stably connected with gold nanorods surface；
Finally, radiotropism isotope in certain proportion68Ga adds the gold nanorods coalition that rgd and dota is stably connected with,
Mix, react 20 minutes, be obtained68Ga-aunrs-rgd polyfunctional molecule probe；
Step 2 is right68Ga-aunrs-rgd polyfunctional molecule probe carries out performance detection
Step 2.1,68Ga-aunrs-rgd polyfunctional molecule probe steady is tested:
By same concentrations68Ga-aunrs-rgd polyfunctional molecule probe and gold nanorods are resuspended to the 10% of equivalent respectively
In nacl solution, then carry out uvs spectral detection, compare both stability differences；
Step 2.2,68Ga-aunrs-rgd polyfunctional molecule fluorescence probe quantum efficiency and extracorporeal receptor binding analysis
First, measure68Cherenkov's photo-quantum efficiency of ga-aunrs-rgd polyfunctional molecule probe: relatively more different68Ga radiates
Same concentration under property activity68Cherenkov's signal photo-quantum efficiency of ga-aunrs-rgd polyfunctional molecule probe, optimization Test
Parameter, obtains luminous efficiency optimized Fluorescence Increasing type68Ga-aunrs-rgd polyfunctional molecule probe；
Secondly, measure68The biology performance of ga-aunrs-rgd polyfunctional molecule probe: adopt68The aunrs-rgd of ga labelling divides
As radioligand, unlabelled aunrs-rgd molecular probe is non-tagged ligand to sub- probe, and analysis is to αvβ3Expression of receptor
Positive glioma u87 cell carries out receptor ligand binding assay；Two kinds of parts are combined with suspension cell, detect their put
Penetrating property dosage and luminous efficiency；
Step 3, tumor bearing nude mice Animal Model
In vitro culture glioma u87 cell, at the right shoulder of nude mice subcutaneous injection of tumor cells several, build Subcutaneous tumor mould
Type, carries out the operation of subsequent step after 2-3 week；
Step 4,68The multi-modality imaging of ga-aunrs-rgd polyfunctional molecule probe:
Step 4.1, pet/ct image data acquiring
Pet/ct data acquisition, mouse tail vein injection are carried out to tumor bearing nude mice using pet/ct imaging system68ga-aunrs-
Carry out pet/ct scanning in different time points after rgd polyfunctional molecule probe, obtain the pet/ct bimodulus of different time points
View data；
Step 4.2, cli/ct image data acquiring
Cli/ct data acquisition, mouse tail vein injection are carried out to described tumor bearing nude mice using cli/ct imaging system68ga-
Obtain multiple spectrum under airtight dark situation, multiple regard in different time points after aunrs-rgd polyfunctional molecule probe
Cherenkov's luminous signal of angle petty action object table and ct view data；
Step 4.3, pet/ct, cli/ct fusing image data:
The pet/ct image that the cli/ct image drawing in described step 4.2 is drawn as in target image and step 4.1 is made
For source images, through pretreatment such as image denoising, enhancings, image segmentation carries out feature extraction, and mutual information image registration, based on figure
As the image co-registration of pixel, obtain68The pet-cli-ct of the tumor region of ga-aunrs-rgd polyfunctional molecule probe targeting is many
Modality imaging figure.
2. the preparation method of the probe for the luminous-ct multi-modality imaging of nucleic-Cherenkov according to claim 1, its
It is characterised by, in step 1.268Difunctional Polyethylene Glycol in the preparation process of ga-aunrs-rgd polyfunctional molecule probe
(opps-peg-nhs) molecular weight of bridging agent is different: the opps-peg-nhs molecular weight being connected with rgd is 2000, with dota even
The opps-peg-nhs molecular weight connecing is 5000.
3. the preparation method of the probe for the luminous-ct multi-modality imaging of nucleic-Cherenkov according to claim 1, its
It is characterised by, in step 3, described subcutaneous tumor model subsequent step again after tumor model is with diameter greater than 0.5cm after 2-3 week
Operation.
4. the preparation method of the probe for the luminous-ct multi-modality imaging of nucleic-Cherenkov according to claim 1, its
It is characterised by, the α of the rgd target tumor blood vessel on gold nanorods surface in step 4vβ3Receptor, specifically binds to tumor.
5. the preparation method of the probe for the luminous-ct multi-modality imaging of nucleic-Cherenkov according to claim 1, its
It is characterised by, in step 4, based on gold nanorods surface same molecular probe radionuclide68The vivo biodistribution process of ga is respectively
Carry out optics and radio nuclide imaging.
Priority Applications (1)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| CN201410370072.5A CN104117075B (en) | 2014-07-30 | 2014-07-30 | Gold nanorod multifunctional probe-based nuclide-cerenkov luminescence-CT multi-mode imaging method |
Applications Claiming Priority (1)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| CN201410370072.5A CN104117075B (en) | 2014-07-30 | 2014-07-30 | Gold nanorod multifunctional probe-based nuclide-cerenkov luminescence-CT multi-mode imaging method |
Publications (2)
| Publication Number | Publication Date |
|---|---|
| CN104117075A CN104117075A (en) | 2014-10-29 |
| CN104117075B true CN104117075B (en) | 2017-01-18 |
Family
ID=51762855
Family Applications (1)
| Application Number | Title | Priority Date | Filing Date |
|---|---|---|---|
| CN201410370072.5A Expired - Fee Related CN104117075B (en) | 2014-07-30 | 2014-07-30 | Gold nanorod multifunctional probe-based nuclide-cerenkov luminescence-CT multi-mode imaging method |
Country Status (1)
| Country | Link |
|---|---|
| CN (1) | CN104117075B (en) |
Families Citing this family (5)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| CN106092973B (en) * | 2016-06-23 | 2019-06-25 | 大连理工大学 | A kind of photo-thermal detection method based on double noble metal nano probes |
| CN106177948A (en) * | 2016-07-22 | 2016-12-07 | 东华大学 | A kind of preparation method of the hollow silicon Venus core shell nano material wrapping up amycin |
| CN106862586B (en) * | 2017-01-20 | 2019-02-15 | 中国科学院高能物理研究所 | One kind is mixed59Fe nanometer gold bar and preparation method thereof |
| CN109453400B (en) * | 2018-10-18 | 2021-07-13 | 中国药科大学 | Radioactive iodine labeled gold nano material and preparation method and application thereof |
| CN109646686B (en) * | 2019-02-13 | 2021-09-07 | 上海师范大学 | Application of metal iridium complex nano particle in nuclide excited phosphorescence imaging |
Citations (3)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| CN102488493A (en) * | 2011-11-15 | 2012-06-13 | 西安电子科技大学 | Small animal living body multi-mode molecule imaging system and imaging method |
| US20130225901A1 (en) * | 2010-04-05 | 2013-08-29 | Nanospectra Biosciences, Inc. | Enhancement of radiation therapy by targeted high-z nanoparticles |
| CN103624266A (en) * | 2012-08-28 | 2014-03-12 | 北京化工大学 | Preparation method for changing length-diameter ratio of gold nanorods and reducing cytotoxicity of gold nanorods |
-
2014
- 2014-07-30 CN CN201410370072.5A patent/CN104117075B/en not_active Expired - Fee Related
Patent Citations (3)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| US20130225901A1 (en) * | 2010-04-05 | 2013-08-29 | Nanospectra Biosciences, Inc. | Enhancement of radiation therapy by targeted high-z nanoparticles |
| CN102488493A (en) * | 2011-11-15 | 2012-06-13 | 西安电子科技大学 | Small animal living body multi-mode molecule imaging system and imaging method |
| CN103624266A (en) * | 2012-08-28 | 2014-03-12 | 北京化工大学 | Preparation method for changing length-diameter ratio of gold nanorods and reducing cytotoxicity of gold nanorods |
Non-Patent Citations (3)
| Title |
|---|
| Integrin αvβ3-targeted gold nanoshells augment tumor vasculature-specific imaging and therapy;Hua Xie .et al;《International Journal of Nanomedicine》;20110126;第260-265页 * |
| 在体小动物切伦科夫发光断层成像研究;胡振华;《中国博士学位论文全文数据库》;20130215;第2页第2段 * |
| 核素切伦科夫光学显像基础研究;马晓伟;《中国优秀硕士学位论文全文数据库医药卫生科技辑》;20140215;第7页第2段 * |
Also Published As
| Publication number | Publication date |
|---|---|
| CN104117075A (en) | 2014-10-29 |
Similar Documents
| Publication | Publication Date | Title |
|---|---|---|
| Weissleder | Scaling down imaging: molecular mapping of cancer in mice | |
| CN104117075B (en) | Gold nanorod multifunctional probe-based nuclide-cerenkov luminescence-CT multi-mode imaging method | |
| Joshi et al. | Exogenous molecular probes for targeted imaging in cancer: focus on multi-modal imaging | |
| Padmanabhan et al. | Nanoparticles in practice for molecular-imaging applications: an overview | |
| Reuveni et al. | Targeted gold nanoparticles enable molecular CT imaging of cancer: an in vivo study | |
| Chen et al. | Dual-modality optical and positron emission tomography imaging of vascular endothelial growth factor receptor on tumor vasculature using quantum dots | |
| Yang et al. | Affibody modified and radiolabeled gold–iron oxide hetero-nanostructures for tumor PET, optical and MR imaging | |
| Lee et al. | RGD peptide–conjugated multimodal NaGdF4: Yb3+/Er3+ nanophosphors for upconversion luminescence, MR, and PET imaging of tumor angiogenesis | |
| Kim et al. | Development and in vivo imaging of a PET/MRI nanoprobe with enhanced NIR fluorescence by dye encapsulation | |
| Yigit et al. | In vivo and ex vivo applications of gold nanoparticles for biomedical SERS imagingi | |
| Hu et al. | In vivo cancer dual-targeting and dual-modality imaging with functionalized quantum dots | |
| Zhang et al. | Affibody-functionalized Ag 2 S quantum dots for photoacoustic imaging of epidermal growth factor receptor overexpressed tumors | |
| Heidt et al. | Multimodal iron oxide nanoparticles for hybrid biomedical imaging | |
| CN109475279A (en) | The imaging system and method for driven for particle, Knowledge based engineering and predictive cancer radiation genomics | |
| Su et al. | Peptide and protein modified metal clusters for cancer diagnostics | |
| Zhu et al. | Dynamic PET and optical imaging and compartment modeling using a dual-labeled cyclic RGD peptide probe | |
| Cai et al. | In a “nutshell”: intrinsically radio-labeled quantum dots | |
| Chen et al. | Multifunctional gold nanocomposites designed for targeted CT/MR/optical trimodal imaging of human non-small cell lung cancer cells | |
| CN106075469A (en) | Gd3+induction gold nano cluster is self-assembled into method and the application of gold nano grain | |
| CN106692993A (en) | Specific targeted magnetic resonance-optical dual-mode imaging probe and preparation method thereof | |
| Jarockyte et al. | Biodistribution of multimodal gold nanoclusters designed for photoluminescence-SPECT/CT imaging and diagnostic | |
| Chen et al. | Highly sensitive electron paramagnetic resonance nanoradicals for quantitative intracellular tumor oxymetric images | |
| Wang et al. | Engineering of 177Lu-labeled gold encapsulated into dendrimeric nanomaterials for the treatment of lung cancer | |
| CN108434469A (en) | A kind of HER2 affinities body68Ga markers and preparation method thereof, application | |
| CN103143037B (en) | Method for synthesizing rare earth metal compound nano cluster and application thereof |
Legal Events
| Date | Code | Title | Description |
|---|---|---|---|
| C06 | Publication | ||
| PB01 | Publication | ||
| C10 | Entry into substantive examination | ||
| SE01 | Entry into force of request for substantive examination | ||
| C14 | Grant of patent or utility model | ||
| GR01 | Patent grant | ||
| CF01 | Termination of patent right due to non-payment of annual fee | ||
| CF01 | Termination of patent right due to non-payment of annual fee |
Granted publication date: 20170118 Termination date: 20170730 |