CN102372771A - Tumor targeted molecule and application thereof - Google Patents
Tumor targeted molecule and application thereof Download PDFInfo
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- CN102372771A CN102372771A CN2010102634446A CN201010263444A CN102372771A CN 102372771 A CN102372771 A CN 102372771A CN 2010102634446 A CN2010102634446 A CN 2010102634446A CN 201010263444 A CN201010263444 A CN 201010263444A CN 102372771 A CN102372771 A CN 102372771A
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Abstract
The invention provides a tumor targeted molecule capable of specifically binding to a plurality of tumors, i.e., ferritin, and a contrast agent for diagnosis of tumor or a therapeutic drug containing the tumor targeted molecule. The contrast agent or the therapeutic drug has the characteristics of no or low toxicity, strong specificity, a small utilization amount, high stability in vivo, etc, and is especially applicable to targeted diagnosis or treatment of malignant tumor tissue, e.g., liver cancer tumor, melanin tumor, lung cancer tumor, breast cancer tumor, colonic/rectal cancer tumor, pancreas cancer tumor, stomach cancer tumor, ovarian cancer, head and neck cancer, neuroglioma, etc.
Description
Technical field
The invention belongs to the biological medicine technology field, particularly the invention provides a kind of novel tumor targeted molecular, it is the ferritin that is assembled by 24 protein protomer molecules, and this protein protomer molecule is the heavy chain and the light chain of people source ferritin.The cage shape cavity structure of 24 subunits that they can assemble by various molecular ratios wherein contains the heavy chain subunit at least.The present invention also provides this tumor targeted molecular ability specific recognition and combines the liver cancer tumour; The melanochrome tumour; The lung cancer tumour; Breast cancer tumour; Knot/rectum cancer tumour; Pancreatic tumour; The cancer of the stomach tumour; Ovarian cancer, malignant tumor tissues such as neurospongioma, the present invention also provides pharmaceutical composition, and it comprises said tumor targeted molecular; The present invention also provides the contrast medium of ultra sonic imaging diagnosis and magnetic resonance image-forming diagnose, and it comprises said tumor targeted molecular.
Background technology
Along with the growth of growth in the living standard and human mean lifetime, and the quickening of modern society's rhythm of life, the change of mode of life, many factors such as pollution of environment, cancer has become the healthy main killer of harm humans.China's malignant tumour incidence also demonstrates three significant variations trend, and the one, number of the infected increases obviously year by year, and sickness rate increased more than 1 times before 20 years, and this situation is on the rise relevant with the certain areas environmental pollution; The 2nd, patient crowd occur two extreme, promptly to suffer from the growth of cancer number the fastest for little crowd of age and elderly population; The 3rd, in all malignant tumours, knot/rectum cancer sickness rate in the crowd increases sharply, and the expert points out that this variation with public's dietary structure is relevant.
The targeting diagnosis of tumour and one of most important research direction of treating the diagnosis and treatment field that has become tumour; At present commonly used is aglucon or antibody that targeted molecular mainly is utilizes the tumor cell surface special molecular is as tumor targeted molecular; Through genetically engineered or chemically modified means aglucon or antibody and other functional moleculars are carried out coupling, thereby bring into play the diagnosis of its cancer target or treat function.Like RGD-4C (CDCRGDCFC) polypeptide; This polypeptide can the selectivity target be combined in the integrin molecule of up-regulated expression in the quick noble cells, utilizes the up-regulated expression of integrin in tumor neogenetic blood vessels, and the RGD-4C polypeptide just can be used as a cancer target aglucon; Many data reports; The RGD-4C polypeptide is coupled to little heat shock protein(HSP) or quantum dot, and perhaps coupling anti-tumor agent comprising salmosin all can show the specificity of tumour cell target and brings into play function.
The invention provides a kind of novel tumor targeted molecular, it is exactly ferritin (ferritin), definitely, is the ferritin that must contain the ferritin heavy chain subunit.In carrying out the carrier experimentation of ferritin as contrast medium; Patented claim person finds; Even the outside surface of ferritin does not have to modify the aglucon that carries cancer target; The ferritin that internal cavity contains magnetic iron oxide particle in the same old way rapidly target be enriched in tumor tissues, and can in the zeugmatography experiment, the tumor tissues blur-free imaging be come out.This explanation ferritin could be independently as tumor targeted molecular! This tumor targeted molecular can be used for the targeting diagnosis or the treatment of malignant tumor tissues such as liver cancer tumour, melanochrome tumour, lung cancer tumour, breast cancer tumour, knot/rectum cancer tumour, pancreatic tumour, cancer of the stomach tumour, ovarian cancer, head and neck cancer, neurospongioma.
Ferritin was come out by Laufberge separation and purification from the spleen of horse in nineteen thirty-seven, had the pH=2.1 of anti-diluted acid the, the pH=12.1 of anti-diluted alkaline the and 70～75 ℃ of characteristics such as unchangeability of anti-comparatively high temps.Ferritin is formed the cage shape cavity structure of high symmetry, its molecular mass 450kD, the about 2～2.5nm of thickness, external diameter 11～13nm, internal diameter 8～9nm by 24 subunits.Iron nuclear is positioned at the protein shell center, forms structure heterogeneous by thousands of ironic hydroxide molecules and hundreds of phosphate molecule, the about 7～8nm of diameter.Plant, prokaryotic organism and non-vertebra liver ferritin are made up of same subunit; And the Mammals ferritin is by heavy chain (heavy chain; H) and light chain (light chain, L) two kinds of subunits are formed in varing proportions, H subunit ferroxidase catalytic activity; It can be oxidized to Fe (III) by catalysis Fe (II), and the L chain does not have this catalytic activity.In ferritin,, cause red stone to be converted into insoluble Fe (III) nuclear because Fe (II) is oxidized to Fe (III).Animal ferritin major part is distributed in liver, spleen, marrow, Skelettmuskel and the intestines mucosa.One of major function of ferritin is to regulate the iron metabolism balance, and in addition, ferritin has vital role aspect the anti-oxidant murder by poisoning of coercing and eliminate part heavy metal and some toxic molecules.The utilization of biotechnology now; Ferritin is developed to the support agent that can carry various functional moleculars; Through the genetic engineering means, connect a RGD-4C polypeptide like Masaki Uchida etc., do not destroying on the cage shape cavity body architecture basics of ferritin at the ferritin outside surface; Ferritin can be under the guiding of RGD-4C polypeptide, the special tumor tissues that is positioned.
The invention provides a kind of novel type radiographic contrast, its outstanding characteristic is with people source ferritin, particularly by containing the people source ferritin that the heavy chain subunit assembles, as tumor targeted molecular; Owing to the cage shape cavity structure characteristics of people source ferritin, it can be as the carrier of contrast medium simultaneously, and with the contrast medium parcel wherein, and the target enrichment is to tumor tissues.The characteristics of this contrast medium are exactly that almost non-toxic property, low cost, particle are little, good water solubility, and high relaxation speed, strong, the long half time of target property, the body internal stability is good.This novel type radiographic contrast can be used for the liver cancer tumour; The melanochrome tumour; The lung cancer tumour; Breast cancer tumour; Knot/rectum cancer tumour; Pancreatic tumour; The cancer of the stomach tumour; Ovarian cancer, the zeugmatography diagnosis of malignant tumor tissues such as neurospongioma.
Diagnostic method of tumors mainly comprises enzyme labeled compound assay, immunologic test, splanchnoscopy at present; Imaging examination etc.; Wherein imaging examination comprises X line perspective again, takes the photograph sheet, zeugmatography, tomoscan, ultrasound investigation, radionuclide scanning and selective angiography or the like; These methods respectively have superiority, and complement one another.Nucleus magnetic resonance (MR I) be nmr imaging technique again, is the another major progress of Medical Imaging behind CT.Since using the eighties in 20th century, it is developed at a terrific speed.Its ultimate principle is: place special magnetic field with hydrogen nuclei in the radio frequency pulse excitation human body human body, cause hydrogen nuclei resonance, and absorb energy.After stopping wave packet, hydrogen nuclei sends the radio signal by CF, and the energy that absorbs is discharged, and is included by external susceptor, handles obtaining image through robot calculator, and this just is called zeugmatography.Early stage in MRI development it is generally acknowledged to need not to use contrast medium can accomplish MRI inspection diagnosis.Along with the widespread use of MRI clinically, people hope that it can improve the resolving power to soft tissue, with the pathology that shows that some are less, a part of difficult disease are become to make a definite diagnosis.This just needs contrast medium further to improve the contrast gradient of nuclear magnetic resonance image.When clinical examination,, make every effort to select suitable spike train and time parameter on the one hand, with actual size, degree and the characteristics of lesion that reflects pathological tissues better in order to improve the resolving power and the contrast gradient of MR I image; Then be devoted to change the MR characteristic parameter of tissue on the other hand, the effort of this respect mainly concentrates on through using relaxation reagent to shorten relaxation time T1 and T2, accelerated relaxation speed (r).This type relaxation reagent is exactly a contrast medium, and the relaxation rate that it can change water proton in the interior local organization of body improves the image contrast of normal position and disease sites, thereby shows the functional status of intracorporeal organ.
Since nineteen eighty-three uses Gd2DTPA to carry out clinical trial, for improving the sensitivity and the target property of contrast medium, reduce its toxicity, people have carried out a large amount of research and development to the MRI contrast medium.The MRI contrast medium of clinical application must satisfy the basic demand of following several respects: (1) low toxicity.Paramagnetic ion gadolinium, manganese, iron etc. such as rare earth of selecting for use as the MRI contrast medium at present and transition metal in it can change the concentration range of nuclear magnetic relaxation speed, all have certain toxicity (2) high relaxation usefulness.(3) target property is strong.(4) good water solubility generally should be greater than 0.5M, osmotic pressure and viscosity etc. should be as far as possible close with blood plasma, so the exploitation of non-ionic contrast agent and application have very important significance.(5) stable in vivo, be easy to excrete.Can excrete in the certain hour after using contrast medium, be unlikely in human body, to accumulate.According to the difference at magnetic center, the MRI contrast medium can be divided into paramagnetic substance, superparamagnetism material and ferromagnetic material three major types.Molecular size according to magnetic is different with particle shape, is divided into several types of small molecules paramagnetic contrast medium, macromolecular paramagnetic contrast medium, particles with superparamagnetism and ferromagnetic particles, nanostructure contrast medium etc. again.
The contrast medium of clinical application at present exists mainly that dosage is big, tumor-targeting is low, and certain problems such as toxic side effect are arranged.Along with the new imaging technique of MR (like MR angiography, perfusion MR, diffusion weighted mri etc.) develop rapidly and in clinical diagnosis, use popularize, the contrast medium that is used for diagnosing tumor also more and more comes into one's own.The contrast medium that development hypotoxicity, low cost, high relaxation speed, target property are by force, the body internal stability is good is a development in future trend.
Novel tumor targeted contrast agent provided by the invention is to utilize ferritin not only as tumor targeted molecular but also as the carrier of contrast medium, can effectively overcome the deficiency of above various contrast medium.Do not introduce under the situation of other polypeptide or inhuman source protein, there be not biocompatibility issues with it in people source ferritin as contrast medium as the naturally occurring albumen of human body, almost non-toxic property; Ferritin can be attached to tumor tissues by target, makes that the consumption of contrast medium is considerably less; Ferritin is at the intravital long half time of people, good stability simultaneously; Because the ferritin good water solubility, particle size is little and even, do not reunite, and the unit protein molecular can contain the magnetic oxygenated iron molecule up to 3000-5000, and relaxation rate is high, and the radiography reinforced effects is good.
The present invention also provides a kind of tumor-targeting drug, and its outstanding characteristic is with people source ferritin, particularly by containing the people source ferritin that the heavy chain subunit assembles, as tumor targeted molecular; Owing to the cage shape cavity structure characteristics of people source ferritin, it can be as the carrier of antitumor drug simultaneously, and with the medicine parcel wherein, and the target enrichment is brought into play the antineoplaston effect to tumor tissues.The characteristics of this tumor-targeting drug are that tumor-targeting is good, and consumption is few, do not have or low spinoff, and the body internal stability is good etc.This tumor-targeting drug can be used for the liver cancer tumour; The melanochrome tumour; The lung cancer tumour; Breast cancer tumour; Knot/rectum cancer tumour; Pancreatic tumour; The cancer of the stomach tumour; Ovarian cancer, the targeted therapy of malignant tumor tissues such as neurospongioma.
Obviously; Ferritin is present in nearly all species; The ferritin of many species (like most of Mammalss) is very close with the sequence of people source ferritin; The ferritin in these sources as the molecule of target tumor and be assembled into aforementioned contrast medium or medicine, also may be had people source ferritin the same or similar function or use range, as long as the cancer target ability of ferritin also exists; And the tumor-targeting function of this ferritin is actually utilized in the practice, and that all is the categories of containing of patent of the present invention.
Obviously; Utilize conventional genetic engineering means; Can express H and the L subunit of producing people source ferritin respectively; And can use independent H or L subunit to be assembled into the complete ferritin that contains 24 subunits, also can H and L subunit be assembled into the complete ferritin that contains 24 subunits by arbitrary proportion.Important feature of the present invention is that the ferritin of these assemblings all possesses the cancer target ability, all can be used as tumor targeted molecular; And along with the content of heavy chain subunit in the ferritin of assembling is high more, tumor-targeting is good more.This type ferritin all can be used in makes tumor target direction contrast agent or tumor-targeting drug, as long as the cancer target ability of ferritin also exists, and the tumor-targeting function of this ferritin is actually utilized in the practice, and that all is the categories of containing of patent of the present invention.
Obviously, utilize genetic engineering means, like point mutation, other amino acid or polypeptide or the like are expressed in brachymemma or connection, all can transform the H and the L subunit of ferritin, make ferritin can carry different types of contrast agent molecule or antibumor molecules.But as long as the agent structure of ferritin also exists, its cancer target ability also exists, and the tumor-targeting function of the ferritin of this transformation is actually utilized in the practice, and that all is the categories of containing of patent of the present invention.
Obviously; Utilize means such as some biological chemistries can aforesaid various forms of ferritins be carried out the modification or the transformation of multi-form means of different, as carry out PEG parcel etc., its purpose can be to reduce immunogenicity; Also can be to improve its transformation period in vivo; Also can be to carry various reagent or the medicines that can be used for tumor imaging or oncotherapy, no matter why, as long as the cancer target ability of the ferritin of those forms also exists; And the tumor-targeting function of this modification or improved ferritin is actually utilized in the practice, and that all is the categories of containing of patent of the present invention.
In addition, along with going deep into of scientific research, the mechanism of ferritin target tumor cell or tissue will progressively be illustrated; The most possible mechanism is that tumour cell shows the receptor protein that has special ferritin; Also possibly be the existence of other non-receptor proteins or molecule, cause ferritin can specific combination at tumour cell or tissue, can predict; The receptor protein of this specific combination ferritin or non-receptor protein; Also possibly become the target spot molecule of diagnosis and treatment tumour as a tumor-marker molecule fully, upgrade better tumor target direction contrast agent or antitumor drug thereby design.
In a word, the invention provides a kind of novel tumor targeted molecular, it is exactly a ferritin, particularly people source ferritin.The characteristics of this tumor targeted molecular are that tumour-specific is high, are applicable to kinds of tumors wide spectrum.The present invention simultaneously also provides diagnosing tumor contrast medium or the medicine that contains this tumor targeted molecular; Characteristics such as this contrast medium or medicine have that nothing or hypotoxicity, tumor-targeting are good, high specificity, consumption are few, body internal stability height are specially adapted to the targeting diagnosis or the treatment of malignant tumor tissues such as liver cancer tumour, melanochrome tumour, lung cancer tumour, breast cancer tumour, knot/rectum cancer tumour, pancreatic tumour, cancer of the stomach tumour, ovarian cancer, head and neck cancer, neurospongioma.
Summary of the invention
The purpose of this invention is to provide a kind of tumor targeted molecular; Said tumor targeted molecular can combine with tumour cell or tissue specificity, thereby can be used to prepare the contrast medium of diagnoses and treatment tumour and the medicine of treatment tumour, particularly; It is following that the present invention provides: 1. tumor targeted molecular; It is characterized in that it is the ferritin of the cage shape cavity structure that is assembled into by 24 protein protomers, this ferritin can be incorporated into tumour cell or tumor tissues by special target; Its binding specificity is high, and speed is fast.
2. as 1 described tumor targeted molecular, it is characterized in that described protein protomer is the genetically engineered remodeling molecule of heavy chain of heavy chain or the people source ferritin of people source ferritin.
3. as 1 described tumor targeted molecular, it is characterized in that described monomeric protein is the genetically engineered remodeling molecule of light chain of light chain or the people source ferritin of people source ferritin.
4. as the described tumor targeted molecular of above 1-3, it is characterized in that described ferritin is the people source ferritin that the light chain of heavy chain and the people source ferritin of people source ferritin assembles by quantitative proportion proportioning arbitrarily.
5. like the described tumor targeted molecular of above 1-4, it is characterized in that described ferritin is a people source ferritin; The heavy chain of described ferritin is the heavy chain of people source ferritin; The light chain of described ferritin is the light chain of people source ferritin.
6. the image-forming contrast medium of a tumour is characterized in that, it contains the described tumor targeted molecular of above 1-4 item; And pharmaceutically acceptable contrast medium or damping fluid or additive or vehicle, and be used for the liver cancer tumour; The melanochrome tumour; The lung cancer tumour; Breast cancer tumour; Knot/rectum cancer tumour; Pancreatic tumour; The cancer of the stomach tumour; Ovarian cancer, the ultra sonic imaging diagnosis of malignant tumor tissues such as neurospongioma and zeugmatography diagnosis.
7. a pharmaceutical composition is characterized in that, it contains the described tumor targeted molecular of above 1-4 item; And pharmaceutically acceptable antitumor drug or damping fluid or additive or vehicle, and being applied to treat various tumours, these tumours comprise: the liver cancer tumour; The melanochrome tumour; The lung cancer tumour; Breast cancer tumour; Knot/rectum cancer tumour; Pancreatic tumour; The cancer of the stomach tumour; Ovarian cancer, malignant tumours such as neurospongioma.
Pcr amplification product 1% agarose gel electrophoresis of accompanying drawing table explanatory view 1. people source ferritin heavy chain cDNA is identified: Lane1 is a molecular weight standard; Lane2 and 3 is HFn cDNA Fig. 2 of 580bp. the 12%SDS-PAGE of the people source ferritin heavy chain of purifying detects: lane1 is the molecular weight of albumen standard; Lane2-4 is the HFn albumen that the purified molecular weight that obtains is 21kDa; Its applied sample amount is respectively 1.25ug, 2.5ug and 5ug.
Specific embodiment
In order more fully to understand and to use the present invention; The following example is provided, need to prove, embodiment just illustrates part characteristic of the present invention; Rather than intention restriction scope of the present invention, and claim of the present invention comprises embodiment but be not limited to embodiment:
Embodiment one, recombinant human heavy chain ferritin (Human H chain Ferritin, preparation HFn)The preparation method of recombination human source ferritin mainly is reference (Masaki U., Michelle L.F., Mark A., Deborah A.W.; Bridgid E.C., Susan B., Ann F.W.; Larissa J., Mark J., Mark J.Y.and TrevorD.; J.AM.Chem.Soc.2006,128,16626) described method is carried out.Practical implementation is following, and the design primer obtains people source ferritin heavy chain gene with the PCR method amplification from normal people's Skelettmuskel cDNA, and upstream primer is: 5 '-A GTC GCC CATATG ACG ACC GCG TCC; Is downstream primer: 5? GCC GGATCC TTA GCTTTC ATT ATC AC.The purpose PCR fragment of size is connected on same pET39b carrier (Novagen) fragment after the NdeI/BamHI double digestion reclaims after the NdeI/BamHI double digestion reclaims near the 550-600bp that amplification obtains, and the HFn gene is accredited as correctly through order-checking.Resulting expression vector is transformed in the e. coli bl21 (DE3).
The picking positive monoclonal is to the fresh LB liquid of 100m (containing the 50ug/ml kantlex) from the LB-agar plate that contains kantlex, 37 ℃ of shaking table overnight cultures; Get overnight culture and contain in the fresh LB substratum of 50ug/ml kantlex to 1L by 1: 20 dilution proportion, 37 ℃ are continued to be cultured to OD value 0.8; The adding final concentration is that the IPTG of 0.5mM induces the recombination high efficiency of HFn to express, and 37 ℃ of abduction deliverings are after 4 hours; The centrifugal collection bacterial precipitation of 4000rpm.
The bacterial precipitation of collecting with the 45ml lysis buffer (100mM Hepes, 50mM NaCl, pH8) resuspended; Add final concentration and be respectively 50ug/ml, the N,O-Diacetylmuramidase of 60ug/ml and 100ug/ml, DNAse and RNAse, after room temperature is placed half a hour, the ultrasonication bacterium, 20000rpm removed deposition in centrifugal 30 minutes; Supernatant was in 72 ℃ of heating 10 minutes, and 20000rpm removed deposition in centrifugal 30 minutes; The gained supernatant carries out separation and purification with superose 6 molecular sieves and obtains highly purified HFn albumen, and the HFn auto-folder is assembled into the ferritin of 24 aggressiveness.280nm measures protein concentration, and-80 ℃ of preservations are subsequent use after the packing.
Embodiment two, contain the preparation of the people source ferritin of red stone nuclearThis preparation process is in N all the time
2Carry out in the environment.The solution adding N that the 8ml of degassing processing is contained 100mM NaCl
2In the encloses container of protection, adding 2ml concentration again is the common 2mg sample (being dissolved in equally in the solution of 100mM NaCl) of HFn of 1mg/ml, keeps under 65 ℃ of envrionment temperatures at recirculated water, and using 50mM NaOH is 8.5 with system pH titration; The mol ratio adding concentration that contains 3000 iron atoms by a cage shape albumen cavity is 12.5mM (NH4)
2Fe (SO4)
2, press H simultaneously
2O
2: Fe (II) is that 1: 3 mol ratio adding concentration is the degassing H of the prepared fresh of 4.17mM
2O
2Fe (II) and H
2O
2The speed of pressing fixed 31.3ul/min adds in the reaction system, with 50mM NaOH system pH titration is stabilized in 8.5 at any time simultaneously.Reaction finishes the unnecessary iron ion freely of 300mM Trisodium Citrate chelating that the back adds 200ul, obtains containing the people source ferritin that red stone is examined with superose 6 molecular sieving, preserves subsequent use.
Embodiment three, tumor target direction contrast agent form images at the NMRS of lotus people knurl nude mice modelWith human lung carcinoma cell line SPCA1 inoculation nude mice subcutaneous (10
7Cell/only), make totally 10 of lotus people lung cancer nude mice models.Be divided into two groups, 5 every group, be respectively observation group and control group.Grow to 1-1.5cm when size when tumour and all nude mices are carried out respectively MRI is flat to be swept; Measuring tumor focus MRI strength of signal is 278; Observation group's nude mice tail vein contains the people HFn ferritin that red stone is examined in the ratio injection of 5mg Fe/kg body weight, and nude mice of control group tail vein is the Fe of 50nm in the ratio injection diameter of 5mgFe/kg body weight
3O
4Magnetic nano particle carries out the MRI enhanced ct scans after half a hour, measuring the tumor focus MRI of observation group strength of signal is 451, and control group tumor focus MRI strength of signal is 325.
With human hepatoma cell strain hep3b inoculation nude mice subcutaneous (107 cells/only), make totally 10 of lotus people liver cancer nude mice models.Be divided into two groups, 5 every group, be respectively observation group and control group.Grow to 1-1.5cm when size when tumour and all nude mices are carried out respectively MRI is flat to be swept; Measuring tumor focus MRI strength of signal is 269; Observation group's nude mice tail vein contains the people HFn ferritin of red stone nuclear in the ratio injection of 5mg Fe/kg body weight; Nude mice of control group tail vein is the Fe3O4 nano particle of 50nm in the ratio injection diameter of 5mgFe/kg body weight; Carry out the MRI enhanced ct scans after half a hour, measuring the tumor focus MRI of observation group strength of signal is 468, and control group tumor focus MRI strength of signal is 372.
Claims (7)
1. tumor targeted molecular is characterized in that: it is the ferritin of the cage shape cavity structure that is assembled into by 24 protein protomers, and this ferritin can be incorporated into tumour cell or tumor tissues by special target.
2. like claims 1 described tumor targeted molecular, it is characterized in that described protein protomer is the genetically engineered remodeling molecule of heavy chain of heavy chain or the ferritin of ferritin.
3. like claims 1 described tumor targeted molecular, it is characterized in that described monomeric protein is the genetically engineered remodeling molecule of light chain of light chain or the ferritin of ferritin.
4. like claims 1 described tumor targeted molecular, it is characterized in that described ferritin is the ferritin that is assembled by quantitative proportion proportioning arbitrarily by the light chain of the heavy chain of claims 2 described ferritins and claims 3 described ferritins.
5. like the described tumor targeted molecular of claims 1-4, it is characterized in that described ferritin is a people source ferritin; The heavy chain of described ferritin is the heavy chain of people source ferritin; The light chain of described ferritin is the light chain of people source ferritin.
6. the image-forming contrast medium of a tumour is characterized in that, it contains the described tumor targeted molecular just like claims 1-4; And pharmaceutically acceptable contrast medium or damping fluid or additive or vehicle, and be used for ultra sonic imaging diagnosis and the zeugmatography diagnosis of malignant tumor tissues such as liver cancer tumour, melanochrome tumour, lung cancer tumour, gland cancer tumour, knot/rectum cancer tumour, pancreatic tumour, cancer of the stomach tumour, ovarian cancer, head and neck cancer, neurospongioma.
7. a pharmaceutical composition is characterized in that, it contains the described tumor targeted molecular just like claims 1-4; And pharmaceutically acceptable antitumor drug or damping fluid or additive or vehicle, and being applied to treat various tumours, these tumours comprise: the liver cancer tumour; The melanochrome tumour; The lung cancer tumour; Breast cancer tumour; Knot/rectum cancer tumour; Pancreatic tumour; The cancer of the stomach tumour; Ovarian cancer, malignant tumours such as neurospongioma.
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Cited By (2)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| CN108027412A (en) * | 2015-07-07 | 2018-05-11 | Q生物公司 | The constant Quantitative MRI Measurement characteristic indication in field |
| CN109982721A (en) * | 2016-10-26 | 2019-07-05 | 西尔欧集团 | It targets and combines malignant tumour rather than carcinoid detectable molecule |
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2010
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Cited By (2)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| CN108027412A (en) * | 2015-07-07 | 2018-05-11 | Q生物公司 | The constant Quantitative MRI Measurement characteristic indication in field |
| CN109982721A (en) * | 2016-10-26 | 2019-07-05 | 西尔欧集团 | It targets and combines malignant tumour rather than carcinoid detectable molecule |
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Application publication date: 20120314 |