CN104587493A - Detection reagents for fast and real-time dynamic monitoring and multimode imaging in early stage of cardio-cerebrovascular related diseases - Google Patents
Detection reagents for fast and real-time dynamic monitoring and multimode imaging in early stage of cardio-cerebrovascular related diseases Download PDFInfo
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Abstract
The invention discloses detection reagents for fast and real-time dynamic monitoring and multimode imaging in the early stage of cardio-cerebrovascular related diseases. The reagents consist of transition metal ions and precious metal ions with good biocompatibility and nano-cluster and porphyrin derivatives thereof; non-intrusive real-time dynamic high-sensitivity fast tracing and monitoring of cardio-cerebrovascular related diseases are realized through accurate targeted fast labeling and imaging of related focus parts; the detection reagents can be applied to accurate detection, imaging and real-time dynamic monitoring of the focus parts of the diseases such as stroke, atherosclerosis, myocardial infarction, cerebral ischemia and cardiac ischemia as well as reperfusion injury thereof; the treatment can be guided by use of related focus images without causing any biological toxic or side effects; and the detection method is simple and easy to implement.
Description
Technical field
The invention belongs to cardiovascular and cerebrovascular vessel technical field, be specifically related to be applied to cardiovascular and cerebrovascular vessel relevant disease early stage, fast, the detectable of real-time dynamic monitoring and multi-modality imaging.
Background technology
Cardiovascular and cerebrovascular disease relates to the disease of blood circulation, and blood circulation refers to hemophoric Organ and tissue in human body, and mainly comprise heart, blood vessel (tremulous pulse, vein, blood capillary) etc., can be subdivided into acute and chronic, be all generally relevant with arteriosclerosis.These diseases have the similar cause of disease, sick process and Therapeutic Method.But, up to the present, for the treatment of cardiovascular and relevant disease thereof, still without special effective ways.So early diagnosis becomes the important channel of improving cardiovascular and cerebrovascular vessel and related disorder patients's survival rate thereof.
Common cardiovascular and cerebrovascular vessel and relevant disease thereof mainly comprise apoplexy, atherosclerosis, myocardial infarction, cerebral ischemia and heart ischemia and reperfusion injury etc. thereof.
Apoplexy is also apoplexy, is the general designation of Chinese medicine to acute cerebrovascular disease.It is suddenly fainted, syncope, the distortion of commissure that occurs together, dysphonia and occur that hemiplegia is a class cerebral blood circulation obstacle disease of cardinal symptom.Because Apoplexy Morbidity is high, mortality rate is high, disability rate is high, relapse rate is high and complication is many, so medical circle is listed as one of three large diseases threatening human health its same coronary heart disease, cancer.
Hurried because falling ill, disease sees multiterminal, and change of illness state is rapid, similar to the benefaction of wind, number change feature, therefore named apoplexy, apoplexy.Primary disease often leaves sequela, and age of onset also tends to rejuvenation, therefore, is threaten human life and the great illness of quality of life.
Atherosclerosis is one group and is called the most common, most important one in arteriosclerotic angiopathy.Be characterized in ductus arteriosus wall thicken hardening, to follow the string and tube chamber reduces, because the lipid outward appearance gathered on endarterium is yellow medicated porridge sample, be therefore called atherosclerosis.Mainly involve big-and-middle-sized tremulous pulse, its clinical manifestation is mainly based on the symptom of afflicted organ.By the difference of artery site of getting involved, primary disease has: aorta and the classification such as Main Branches, coronary artery, carotid artery, cerebral arteries, renal artery, Mesenteric artery and artery of extremity be atherosis thereof.Generally show as and may occur mental and flag.
Myocardial infarction is myocardial infarction again, and myocardial infarction is coronary occlusion, blood flow ceases, makes part cardiac muscle, because of serious persistency ischemia, local necrosis occur.Have acutely and comparatively lasting retrosternal pain clinically, heating, leukocytosis, erythrocyte sedimentation rate are accelerated, and serum cardiac enzyme activity increases and Progressive symmetric erythrokeratodermia ECG Change, and arrhythmia, shock or heart failure can occur.
Cerebral ischemia and heart ischemia and reperfusion injury thereof, in recent years. along with the progress of shock treatment and artery bypass art, thrombolytic therapy, percutaneous intracavity Coronary angioplasty, department of cardiac surgery extracorporeal circulation, cardio-pulmonary-cerebral resuscitation, the foundation of the method such as the replantation of amputated limb and organ transplantation and applying, obtains blood reperfusion after making many histoorgan ischemias again.In most cases, postischemic reperfusion can make tissue organ function be restored, and the structure of damage is repaired, conditions of patients improvement rehabilitation; But postischemic reperfusion sometimes. tissue, organ dysfunction not only can not be made to recover, add re-organized, the dysfunction of organ and structural damage on the contrary.This on ischemia basis, recover blood flow after tissue injury increase the weight of on the contrary, the phenomenon that irreversible damage even occurs is called ischemical reperfusion injury.
Generally speaking, cardiovascular and cerebrovascular vessel and relevant disease thereof all bring huge society and financial burden for individual and entire society, along with the progress of science and technology, have had multiple Imaging Method and biomarker to be applied to Clinical detection.Existing being usually used in diagnoses the method for cardiovascular and cerebrovascular vessel and relevant disease thereof to have x-ray, electrocardiogram, conventional CT, nuclear magnetic resonance etc. multiple.But these methods all have certain limitation, find the early diagnosis of a kind of sensitivity Wicresoft's detection technique special again to cardiovascular and relevant disease thereof particularly important.Up to the present, the report that energy type carries out in early days cardiovascular and cerebrovascular vessel and relevant disease thereof, reagent that is quick, real-time, multi-modality imaging is relevant is had not yet to see.
Summary of the invention
Goal of the invention: for the defect of current existing detection technique, the invention discloses that to be applied to cardiovascular and cerebrovascular vessel relevant disease early stage, fast, the detectable of real-time dynamic monitoring and multi-modality imaging, by the image checking reagent of biology in situ fixed point effect to the accurate targeting Fast Labeling of relevant lesions position, realize the highly sensitive quick spike of Real-time and Dynamic and the monitoring of the cardiovascular and cerebrovascular vessel relevant disease of non-intrusion type, apoplexy can be applied to, atherosclerosis, myocardial infarction, the detection of cerebral ischemia and the relevant disease such as heart ischemia and reperfusion injury thereof, imaging and real-time dynamic monitoring, and the image-guided realization of relevant focus can be utilized accurately effectively to treat, inanimate object toxic and side effects, detection method is simple and easy to do.
Technical scheme: in order to solve the problems of the technologies described above, the invention provides be applied to cardiovascular and cerebrovascular vessel relevant disease early stage, fast, the detectable of real-time dynamic monitoring and multi-modality imaging, described detectable is made up of metal ion and nano-cluster reagent thereof and derivatives of porphyrin, and by the effect of biology in situ fixed point to the accurate targeting Fast Labeling of relevant lesions position and image checking.
Described metal ion is the mixture of a kind of in gold ion, silver ion, platinum ion, zinc ion etc. or any two kinds.
Described cardiovascular and cerebrovascular vessel relevant disease refers to the relevant disease of apoplexy, atherosclerosis, myocardial infarction, cerebral ischemia and heart ischemia and reperfusion injury thereof.
Described nano-cluster is the mixture of a kind of in gold nanoclusters, silver nanoclusters, platinum cluster or any two kinds.
Described derivatives of porphyrin is sulfonic group derivatives of porphyrin.
Described detectable is in the application of the early stage context of detection fast of cardiovascular and cerebrovascular vessel relevant disease.
Described application, comprise the following steps: when this detectable is used for apoplexy imaging, in the apoplexy model mouse body that metal ion and nano-cluster reagent thereof and derivatives of porphyrin are brought out to normal control model mouse and blood vessel injury by tail vein injection or local injection, metal ion and nano-cluster thereof and derivatives of porphyrin can fast in the hypoxic-ischemic lesions position enrichments of brain, be combined small animal living body phosphorimager, CT, ultrasonic and MRI image instrument carry out imaging to model mouse.
Described application, its concrete steps are:
1) blood vessel injury is utilized to bring out animal models such as building apoplexy model mouse;
2) by concentration aseptic for 0.1 ~ 0.5 mL be the metal ion of 0.1 ~ 100 mmol/L and nano-cluster thereof and derivatives of porphyrin reagent solution, be expelled in normal control model mouse and apoplexy model mouse body, through highly sensitive quick spike and the monitoring of the Real-time and Dynamic of the non-intrusion type of 1 ~ 72 hour, observation body-internal-circulation realizes the specific enrichment of medicine at diseased region and the accurate targeting Fast Labeling imaging of relevant lesions position on apoplexy model mouse;
3) carry out imaging with living body fluorescent imager, CT and MRI image instrument and it is carried out qualitative and quantitative analysis
Beneficial effect: the present invention is compared with art methods, have the following advantages and effect: the reagent that the present invention adopts is by the excellent transition metal ions of biocompatibility, the nano-cluster of precious metal ion and biology in situ thereof and derivatives of porphyrin form, the accurate targeting labelling of relevant lesions position is realized and fast imaging detects by the specificity microenvironment such as hypoxic-ischemic in biology in situ fixed point effect targeting body, realize the highly sensitive quick spike of Real-time and Dynamic and the monitoring of the cardiovascular and cerebrovascular vessel relevant disease of non-intrusion type, apoplexy can be applied to, atherosclerosis, myocardial infarction, the detection of cerebral ischemia and the relevant disease such as heart ischemia and reperfusion injury thereof, imaging and real-time dynamic monitoring, and the image-guided realization of relevant focus can be utilized accurately effectively to treat, inanimate object toxic and side effects, detection method is simple and easy to do, effectively prevent the bio-toxicity that the chemical reagent introduced in Conventional nano material synthesis processes and nano material stabilizing agent cause organism, avoid simultaneously and to be eliminated after Conventional nano material is easily caught by reticuloendothelial system thus the shortcoming of lesion tissue can not be arrived, to realize the analysis of live body targeted imaging.Result shows: by the image checking such as CT, ultrasonic, fluorescence and MRI can fast model of cognition Mus cardiovascular morbidity position and be enriched in this region, realize the accurate labelling of targeting lesions position.These results suggest that such reagent can realize early stage, quick, real-time, multi-modal (as CT, ultrasonic, fluorescence and the MRI etc.) image checking to cardiovascular related diseases.This invention can realize the imaging of cardiovascular and cerebrovascular vessel relevant disease lesions position of not damaged, original position, Real-time and Dynamic targeting, carries out polymorphic with multi-modal synchronous diagnosis and accurately targeting location and treatment, has wide medical application prospect.
Accompanying drawing explanation
Fig. 1 apoplexy model mouse tail vein injection, different time points head focal zone fluorescence intensity change figure.
Detailed description of the invention
The following description is only exemplary and be not to limit the disclosure, application or purposes in essence.
embodiment 1be applied to the metal ion of early stage, quick, real-time, the multi-modal detection of apoplexy and the detectable of nano-cluster and derivatives of porphyrin thereof
First prepare the excellent metal ion of biocompatibility and nano-cluster thereof and derivatives of porphyrin reagent, concrete steps are: metal ion and nano-cluster thereof and derivatives of porphyrin reagent are dissolved in ultra-pure water respectively, and being all mixed with concentration is 0.1 ~ 100 mmol/L.Described metal ion is the mixture of a kind of in gold ion, silver ion, platinum ion, zinc ion etc. or any two kinds.Described nano-cluster is the mixture of a kind of in gold nanoclusters, silver nanoclusters, platinum cluster or any two kinds; Described porphyrin is sulfonic group derivatives of porphyrin.
When this reagent is used for apoplexy imaging, in the animal bodies such as the apoplexy model mouse that metal ion and nano-cluster reagent thereof and derivatives of porphyrin reagent are brought out to normal control model mouse and blood vessel injury by tail vein injection or local injection, metal ion and nano-cluster thereof and derivatives of porphyrin reagent can fast in the lesions position enrichments such as hypoxic-ischemic of brain, are combined the image instruments such as small animal living body phosphorimager, CT, ultrasonic and MRI and carry out imaging to animals such as model mouses.Relevant concrete steps comprise:
1) utilize blood vessel injury to bring out and build apoplexy model mouse;
2) by concentration aseptic for 0.1 ~ 0.5 mL be the metal ion of 0.1 ~ 100 mmol/L and nano-cluster thereof and derivatives of porphyrin reagent solution, be expelled on normal control model mouse and apoplexy model mouse, through highly sensitive quick spike and the monitoring of the Real-time and Dynamic of the non-intrusion type of 1 ~ 72 hour, observation body-internal-circulation realizes the specific enrichment of medicine at diseased region and the accurate targeting Fast Labeling imaging of relevant lesions position on apoplexy model mouse;
3) with image instruments such as living body fluorescent imager, CT, ultrasonic and MRI, living animal and brain thereof are carried out imaging and carried out qualitative and quantitative analysis to it.
Such as, when utilizing the imaging of living body fluorescent imager, choose 1 hour respectively, the different time points such as 4 hours, 8 hours, 12 hours, 24 hours, 48 hours, then this experimental model Mus 5% isoflurane is carried out gas anesthesia, be placed on small animal living body imager operating platform, select 420nm and 480nm equiwavelength to excite the image collecting living animal brain lesions region.
Result shows, normal control model mouse head unstressed configuration produces, and the fluorescence intensity of lesion region presents the change first increasing and weaken afterwards along with the time on apoplexy model mouse, illustrate that the preparation such as ion or nano-cluster in reagent can fixed point effect specifically or be enriched in the lesion region such as hypoxic-ischemic, then metabolism gradually again.Apoplexy model mouse tail vein injection, different time points head focal zone fluorescence intensity change is see Fig. 1.
Embodiment 2 is applied to the metal ion of early stage, quick, real-time, the multi-modal detection of atherosclerosis and nano-cluster thereof and derivatives of porphyrin reagent.
When this reagent is used for atherosclerosis imaging, by metal ion and the reagent solution such as nano-cluster reagent and derivatives of porphyrin thereof by tail vein injection or local injection in the animal bodies such as normal control model mouse and Atherosclerosis Model Mus, metal ion and nano-cluster thereof and derivatives of porphyrin reagent can fast in endovascular lesions position enrichments, use the image instrument such as small animal living body phosphorimager, CT, ultrasonic and MRI to carry out imaging to model mouse.Relevant concrete steps comprise:
1) animal models such as Atherosclerosis Model Mus are built;
2) by concentration aseptic for 0.3 mL be metal ion and the reagent solution such as nano-cluster and derivatives of porphyrin thereof of 50 mmol/L, be expelled on the animal model such as normal control model mouse and Atherosclerosis Model Mus, through highly sensitive quick spike and the monitoring of the Real-time and Dynamic of the non-intrusion type of 1 ~ 72 hour, observation body-internal-circulation realizes the specific enrichment of medicine at diseased region and the accurate targeting fast imaging labelling of relevant lesions position on Atherosclerosis Model animal;
3) with image instruments such as living body fluorescent imager, CT, ultrasonic and MRI, lesion region with it living animal is carried out imaging and carried out qualitative and quantitative analysis to it.
Such as, when utilizing the imaging of living body fluorescent imager, choose 1 hour respectively, the different time points such as 4 hours, 8 hours, 12 hours, 24 hours, 48 hours, then this experimental model Mus 5% isoflurane is carried out gas anesthesia, be placed on small animal living body imager operating platform, select 420nm and 480nm equiwavelength to excite to collect the image of living animal lesion region with it.
Result shows, normal control model mouse with it unstressed configuration produces, and the fluorescence of Atherosclerosis Model Mus visible plaques shape with it, illustrate that the preparation such as ion or nano-cluster in reagent can fixed point effect specifically or be enriched in the lesion region such as hypoxic-ischemic.
Step 2) described metal ion is the mixture of gold ion, zinc ion; Described nano-cluster is gold nanoclusters; Described porphyrin is sulfonic group derivatives of porphyrin.
Embodiment 3
Identical with embodiment 2, the metal ion platinum ion of difference to be the aseptic concentration of 0.1mL adopted be 100 mmol/L; Described nano-cluster is silver nanoclusters; Described derivatives of porphyrin is sulfonic group derivatives of porphyrin.Result is identical with embodiment 2.
Embodiment 4
Identical with embodiment 2, the metal ion of difference to be the aseptic concentration of 0.5 mL adopted be 0.1 mmol/L.Described metal ion is the mixture of silver ion, zinc ion; Described nano-cluster is platinum cluster; Derivatives of porphyrin is sulfonic group derivatives of porphyrin.Result is identical with embodiment 2.
More than show and describe ultimate principle of the present invention and principal character and advantage of the present invention.The technical staff of the industry should understand; the present invention is not restricted to the described embodiments; what describe in above-described embodiment and description just illustrates principle of the present invention; without departing from the spirit and scope of the present invention; the present invention also has various changes and modifications, and these changes and improvements all fall in the claimed scope of the invention.Application claims protection domain is defined by appending claims and equivalent thereof.
Claims (8)
1. be applied to cardiovascular and cerebrovascular vessel relevant disease early stage, fast, the detectable of real-time dynamic monitoring and multi-modality imaging, it is characterized in that, described detectable is made up of metal ion and nano-cluster reagent thereof and derivatives of porphyrin, and by the effect of biology in situ fixed point to the accurate targeting Fast Labeling of relevant lesions position and image checking.
2. according to claim 1 be applied to cardiovascular and cerebrovascular vessel relevant disease early stage, fast, the detectable of real-time dynamic monitoring and multi-modality imaging, it is characterized in that, described metal ion is the mixture of a kind of in gold ion, silver ion, platinum ion, zinc ion or any two kinds.
3. according to claim 1 be applied to cardiovascular and cerebrovascular vessel relevant disease early stage, fast, the detectable of real-time dynamic monitoring and multi-modality imaging, it is characterized in that, described cardiovascular and cerebrovascular vessel relevant disease refers to the relevant disease of apoplexy, atherosclerosis, myocardial infarction, cerebral ischemia and heart ischemia and reperfusion injury thereof.
4. according to claim 1 be applied to cardiovascular and cerebrovascular vessel relevant disease early stage, fast, the detectable of real-time dynamic monitoring and multi-modality imaging, it is characterized in that, described nano-cluster is the mixture of a kind of in gold nanoclusters, silver nanoclusters, platinum cluster or any two kinds.
5. according to claim 1 be applied to cardiovascular and cerebrovascular vessel relevant disease early stage, fast, the detectable of real-time dynamic monitoring and multi-modality imaging, it is characterized in that, described derivatives of porphyrin is sulfonic group derivatives of porphyrin.
6. detectable according to claim 1 is in the application of the early stage context of detection fast of cardiovascular and cerebrovascular vessel relevant disease.
7. application according to claim 6, it is characterized in that, comprise the following steps: when this detectable is used for apoplexy imaging, in the apoplexy model mouse body that metal ion and nano-cluster reagent thereof and derivatives of porphyrin are brought out to normal control model mouse and blood vessel injury by tail vein injection or local injection, metal ion and nano-cluster thereof and derivatives of porphyrin can fast in the hypoxic-ischemic lesions position enrichments of brain, be combined small animal living body phosphorimager, CT, ultrasonic and MRI image instrument carry out imaging to model mouse.
8. the application described in claim 6 or 7, is characterized in that, its concrete steps are:
1) utilize blood vessel injury to bring out and build apoplexy model mouse;
2) by concentration aseptic for 0.1 ~ 0.5 mL be the metal ion of 0.1 ~ 100 mmol/L and nano-cluster thereof and derivatives of porphyrin reagent solution, be expelled in normal control model mouse and apoplexy model mouse body, through highly sensitive quick spike and the monitoring of the Real-time and Dynamic of the non-intrusion type of 1 ~ 72 hour, observation body-internal-circulation realizes the specific enrichment of medicine at diseased region and the accurate targeting Fast Labeling imaging of relevant lesions position on apoplexy model mouse;
3) with living body fluorescent imager, CT and MRI image instrument imaging is carried out to brain and it is carried out qualitative and quantitative analysis.
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| PCT/CN2015/074688 WO2016123841A1 (en) | 2015-02-03 | 2015-03-20 | Multimodality imaging preparation used for detecting senile dementia and cardio-cerebrovascular diseases and application thereof |
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| WO2020029098A1 (en) * | 2018-08-07 | 2020-02-13 | 苏州大学张家港工业技术研究院 | Platinum sulfide protein nanoparticle having near-infrared photothermal effect and multi-modal imaging function, preparation method therefor and application thereof |
| CN116628457A (en) * | 2023-07-26 | 2023-08-22 | 武汉华康世纪医疗股份有限公司 | Harmful gas detection method and device in operation of magnetic resonance equipment |
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| CN105214103A (en) * | 2015-10-14 | 2016-01-06 | 东南大学 | Detect fast in early days for malignant tumor and cardiovascular and cerebrovascular vessel relevant disease and the metal ion reagent of multi-modality imaging and image preparation |
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