CN110283120A - A kind of monitoring of CART cytokines and/or drug, preparation method and its application of outcome prediction - Google Patents
A kind of monitoring of CART cytokines and/or drug, preparation method and its application of outcome prediction Download PDFInfo
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- CN110283120A CN110283120A CN201910602155.5A CN201910602155A CN110283120A CN 110283120 A CN110283120 A CN 110283120A CN 201910602155 A CN201910602155 A CN 201910602155A CN 110283120 A CN110283120 A CN 110283120A
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- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07D—HETEROCYCLIC COMPOUNDS
- C07D215/00—Heterocyclic compounds containing quinoline or hydrogenated quinoline ring systems
- C07D215/02—Heterocyclic compounds containing quinoline or hydrogenated quinoline ring systems having no bond between the ring nitrogen atom and a non-ring member or having only hydrogen atoms or carbon atoms directly attached to the ring nitrogen atom
- C07D215/16—Heterocyclic compounds containing quinoline or hydrogenated quinoline ring systems having no bond between the ring nitrogen atom and a non-ring member or having only hydrogen atoms or carbon atoms directly attached to the ring nitrogen atom with hetero atoms or with carbon atoms having three bonds to hetero atoms with at the most one bond to halogen, e.g. ester or nitrile radicals, directly attached to ring carbon atoms
- C07D215/20—Oxygen atoms
- C07D215/24—Oxygen atoms attached in position 8
- C07D215/26—Alcohols; Ethers thereof
- C07D215/30—Metal salts; Chelates
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- G—PHYSICS
- G01—MEASURING; TESTING
- G01N—INVESTIGATING OR ANALYSING MATERIALS BY DETERMINING THEIR CHEMICAL OR PHYSICAL PROPERTIES
- G01N30/00—Investigating or analysing materials by separation into components using adsorption, absorption or similar phenomena or using ion-exchange, e.g. chromatography or field flow fractionation
- G01N30/02—Column chromatography
- G01N30/04—Preparation or injection of sample to be analysed
- G01N30/06—Preparation
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- G—PHYSICS
- G01—MEASURING; TESTING
- G01N—INVESTIGATING OR ANALYSING MATERIALS BY DETERMINING THEIR CHEMICAL OR PHYSICAL PROPERTIES
- G01N30/00—Investigating or analysing materials by separation into components using adsorption, absorption or similar phenomena or using ion-exchange, e.g. chromatography or field flow fractionation
- G01N30/90—Plate chromatography, e.g. thin layer or paper chromatography
Abstract
The invention discloses a kind of monitoring of CART cytokines and/or drug, preparation method and its application of outcome prediction, the present invention is used68CART cell is marked in Ga-oxine, develops the drug of the new CART cytokines monitoring of one kind and/or outcome prediction,68The irradiation to human normal tissue and CART cell can be greatly reduced in Ga-oxine, while realizing the early stage distribution for CAR-T, and outcome prediction, the research such as Visual retrieval is expected to the research and development for the cytotoxic drug that power-assisted precisely targets.
Description
Technical field
The invention belongs to oncotherapy technical field of pharmaceuticals, and in particular to a kind of monitoring of CART cytokines and/or treat
Imitate drug, preparation method and its application of prediction.
Background technique
Currently, the treatment method of malignant tumour mainly has the multiple means such as operation, chemotherapy, radiotherapy, various treatment means are equal
Certain therapeutic effect can be obtained, but also all Shortcomings or disadvantage.Tumor immunology treatment is used as a kind of emerging therapy, has sent out
It transforms into as the 4th kind of tumor treatment model after operation, chemotherapy and radiation.Immunotherapy of tumors is quickly grown in recent years,
In that attract most attention is exactly U.S. immunologist James Ai Lisen (James P Alison) in 2018 and Japanese immunology
This multitudinous help (Tasuku Honjo) of family wins Nobel prize's soul to reward it what tumour immunity field was made and dash forward
It contributes out.According to different mechanism of action, immunotherapy of tumors drug is divided into six classes: targeting T-cells immunomodulator, other exempt from
Epidemic disease regulator, tumor vaccine, cell therapy, oncolytic virus, CD3 targeting bispecific antibody etc., from September, 2017 by 2018
September, cell therapy is the rapidest in immunotherapy of tumors field development speed, speedup 113%, wherein grinds in preclinical
The cytotoxic drug for studying carefully the stage increases to 448 by 179, and the cytotoxic drug in clinicalⅰstage conceptual phase increases to 176 by 112
A, the cytotoxic drug in clinical II phase conceptual phase increases to 227 by 109.The Chimeric antigen receptor T of immunotherapy of tumors
Cell (Chimeric Antigen Receptor T-Cell Immunotherapy, CAR-T) by extracellular antigen binding domain (by
Light chain (VL) and heavy chain (VH) from monoclonal antibody form, and centre is connected by the hinge area with toughness forms single-stranded resist
Body, trans-membrane region and intracellular signal transduction district's groups at).CAR-T therapy is the T lymphocyte using patient itself, by experiment
Room is transformed again, is had the receptor and costimulatory molecules of identification tumour antigen on loading, is fed back again after amplification in vitro into patient
In vivo, to identify and attack the tumour cell of itself.CART cell therapy is significant in efficacy for blood tumor, case the most well-known
Example is the Emily Whitehead moral (Emily Whitehead) with recurrent and refractory leukaemia being only six years old, 2012
Year becomes the child patient of first reception test CAR-T therapy, and internal cancer cell completely disappears after treatment, and is treating
7 years after still grow up healthy and sound.In view of the protrusion curative effect of CAR-T therapy, in August, 2017, the whole world it is first for treat 25 years old with
Lower recurrent and refractory B-lineage Acute Lymphocyte Leukemia (r/rB-ALL) targeting CD19 CAR-T drug (trade name:
Kymriah) ratified to list by U.S. Food and Drug Administration (FDA).Treat recurrent and refractory large B cell October in the same year
The CAR-T drug (trade name: Yescarta) of lymthoma (r/rLBCL) gets the Green Light listing.Both CAR-T therapy medicines
Listing indicates the arrival in cell therapy epoch.
Blood tumor treatment aspect, CART cell is significant in efficacy, but most tumor patients are solid tumor, due to lacking
The specific target spot only existed in tumour cell without expressing in health tissues, CAR-T treatment exist in treatment of solid tumors
Targeting is low and big wait of toxicity is challenged.Such as, Her2/ERBB2 is solid tumor monoclonal antibody medicine, the antibody coupling medicine by clinical verification
The target spot of object, the high expression in kinds of tumors tissue target the CAR-T of Her2 in first case clinical trial due to combining simultaneously
Killed the cell that Her2 expresses on a small quantity in lung, Pulmonary Function caused to be lost and then dead, thus real-time monitoring CAR-T cell into
Distribution and action target spot after entering in vivo etc. become critical issue urgently to be resolved.In vivo currently used for monitoring infused cells
Method includes the serum analysis of cell factor relevant to T cell activation, the direct counting of tumor specific T cells in peripheral blood
And tumor biopsies biopsy etc., but cannot achieve the internal distribution and the monitoring of dynamic metabolism of immunocyte.
Summary of the invention
The purpose of this section is to summarize some aspects of the embodiment of the present invention and briefly introduce some preferable implementations
Example.It may do a little simplified or be omitted to avoid our department is made in this section and the description of the application and the title of the invention
Point, the purpose of abstract of description and denomination of invention it is fuzzy, and this simplification or omit and cannot be used for limiting the scope of the invention.
In view of above-mentioned technological deficiency, the present invention is proposed.
Therefore, as one aspect of the present invention, the present invention overcomes the deficiencies in the prior art, provides one kind
The drug of the monitoring of CART cytokines and/or outcome prediction.
In order to solve the above technical problems, the present invention provides the following technical scheme that a kind of CART cytokines monitoring and/or
The drug of outcome prediction, in which: the drug includes68Ga-oxine, structural formula are as follows:
As another aspect of the present invention, the present invention overcomes the deficiencies in the prior art, and it is thin to provide preparation CART
The method of the drug of born of the same parents' monitored in vivo and/or outcome prediction.
In order to solve the above technical problems, the present invention provides the following technical scheme that a kind of prepare the monitoring of CART cytokines
And/or the method for the drug of outcome prediction comprising,
ITG 740MBq is eluted with HCl68Ge/68Ga generator, takes leacheate；
The pH that NaAc solution adjusts leacheate is added；
Oxine solution is added to mix, react, obtains68Ga-oxine。
One kind of method as the drug of the present invention for preparing the monitoring of CART cytokines and/or outcome prediction is excellent
Select scheme: the HCl is the 0.05mol/L of 4mL.
One kind of method as the drug of the present invention for preparing the monitoring of CART cytokines and/or outcome prediction is excellent
Select scheme: it is described to take leacheate, for the 2~3mL of leacheate for taking elution crest segment.
One kind of method as the drug of the present invention for preparing the monitoring of CART cytokines and/or outcome prediction is excellent
Select scheme: the pH that NaAc solution is added and adjusts leacheate, wherein the solubility of the NaAc solution is 1mol/L.
One kind of method as the drug of the present invention for preparing the monitoring of CART cytokines and/or outcome prediction is excellent
Select scheme: the pH that NaAc solution is added and adjusts leacheate, wherein the pH for adjusting leacheate is 5~6.
One kind of method as the drug of the present invention for preparing the monitoring of CART cytokines and/or outcome prediction is excellent
Select scheme: the addition oxine solution mixes, and is that oxine powder is dissolved in 10% acetic acid solution, compound concentration is
The oxine solution of 1mg/mL.
One kind of method as the drug of the present invention for preparing the monitoring of CART cytokines and/or outcome prediction is excellent
Select scheme: the reaction is 37 DEG C of 10~60min of reaction.
As another aspect of the present invention, the present invention overcomes the deficiencies in the prior art, provides described68Ga-
Application of the oxine in the drug for preparing the monitoring of CART cytokines and/or outcome prediction.
In order to solve the above technical problems, the present invention provides the following technical scheme that described68Ga-oxine is in preparation CART
Application in the drug of cytokines monitoring and/or outcome prediction comprising, take 10~50 μ Ci68Ga-oxine solution and 106
A CART cell is incubated for 10min in room temperature PBS.
As of the present invention68Ga-oxine is in the drug for preparing the monitoring of CART cytokines and/or outcome prediction
Application preferred embodiment: it is described68Ga-oxine label CART Cell viability be greater than 90%, and68Ga-oxine is used for CART
Irradiation dose is low in body when cell early stage distribution monitoring, only89The 3-5% of Zr-oxine labeling method.
Beneficial effects of the present invention: the present invention uses68CART cell is marked in Ga-oxine, develops a kind of new
CART cell curative effect/forecast of distribution drug,68The irradiation to human normal tissue and CART cell can be greatly reduced in Ga-oxine,
Simultaneously realize for CAR-T early stage distribution, outcome prediction, Visual retrieval etc. research, be expected to power-assisted precisely target it is thin
The research and development of born of the same parents' class drug.
Detailed description of the invention
In order to illustrate the technical solution of the embodiments of the present invention more clearly, required use in being described below to embodiment
Attached drawing be briefly described, it should be apparent that, drawings in the following description are only some embodiments of the invention, for this
For the those of ordinary skill of field, without any creative labor, it can also be obtained according to these attached drawings other
Attached drawing.Wherein:
Fig. 1 is68Influence diagram of the pH value of leacheate to yield in the preparation process of Ga-oxine.
Fig. 2 is68Influence diagram of the reaction time to yield in the preparation process of Ga-oxine.
Fig. 3 is68Ga-oxine and89Zr-oxine marks CART cell infusion NOG mouse Micro-PET scanning figure.
Fig. 4 are as follows:68Ga-oxine and89Tendency chart is distributed and is metabolized in vivo after Zr-oxine label CART cell.
Specific embodiment
In order to make the foregoing objectives, features and advantages of the present invention clearer and more comprehensible, right combined with specific embodiments below
A specific embodiment of the invention is described in detail.
In the following description, numerous specific details are set forth in order to facilitate a full understanding of the present invention, but the present invention can be with
Implemented using other than the one described here other way, those skilled in the art can be without prejudice to intension of the present invention
In the case of do similar popularization, therefore the present invention is not limited by the specific embodiments disclosed below.
Secondly, " one embodiment " or " embodiment " referred to herein, which refers to, may be included at least one realization side of the invention
A particular feature, structure, or characteristic in formula." in one embodiment " that different places occur in the present specification not refers both to
The same embodiment, nor the individual or selective embodiment mutually exclusive with other embodiments.
Instrument and device:
Mini-Scan TLC thin layer radioactive scanning instrument: Bio SCAN company, the U.S.；3 type activity meter of Curiementor:
German PTW company；AC 210S type electronic balance: German Sartorius company；Agilengt5TC-C18 (2) chromatographic column: the U.S.
Agilent company；C18 column: Waters, US；MicroPET: German Simens company；Toy Anesthesia machine: SAR-
830/P type, CWE company, the U.S..
Main material and reagent:
The purchase of oxine:Sigma company；68Ga: Jiangsu Inst of Atomic Medical Sciences elution；Hydrochloric acid, methylene chloride, methanol,
Triethylamine: Sinopharm Chemical Reagent Co., Ltd.；Isoflurane: Shanghai Abbott GmbH. & Co. Kg.
Cell and experimental animal:
CAR-T cell: Shanghai You Kadi company provides；NOG mouse: 2, Shanghai You Kadi company provides, by Jiangsu Province
Atomic medicine research institute Experimental Animal Center Clean Facility IVC system is normally raised；Experimental animal uses credit number: SCXK
(Soviet Union) 2014-0023.
The drug of CART cytokines monitoring of the present invention and/or outcome prediction68The preparation method of Ga-oxine:
68The preparation of Ga-oxine: ITG 740MBq is eluted with the 0.05mol/L HCl of 4mL68Ge/68Ga generator, takes
2~3mL of crest segment of leacheate；It takes the leacheate that the NaAc solution of 1mol/L is added, adjusts the pH to 5~6 of leacheate；It will
Oxine powder is dissolved in 10% acetic acid solution, and compound concentration is the oxine solution of 1~2mg/mL, mixes concussion；By leacheate
It is mixed at room temperature with 10~20 μ L oxine solution, 37 DEG C of 10~60min of reaction.
TLC Quality Control: it prepares solvent (methylene chloride: methanol=9.5:0.5+1% triethylamine), carrier is glass fibre
Paper；It dries up after extracting reaction solution point sample, is unfolded with solvent, detect mark rate, same method using TLC thin layer radioactive scanning instrument
Monitor external 2h internal stability.
Embodiment 1:
68The preparation of Ga-oxine: ITG 740MBq is eluted with the 0.05mol/L HCl of 4mL68Ge/68Ga generator, takes
The crest segment 3mL of leacheate；It takes leacheate described in wherein 500 μ L that the NaAc solution of 1mol/L is added, adjusts the pH to 5 of leacheate；
Oxine powder is dissolved in 10% acetic acid solution, compound concentration is the oxine solution of 1mg/mL, mixes concussion；By leacheate with
10 μ L oxine solution mix at room temperature, 37 DEG C of reaction 10min.
TLC Quality Control: it prepares solvent (methylene chloride: methanol=9.5:0.5+1% triethylamine), carrier is glass fibre
Paper；It dries up after extracting reaction solution point sample, is unfolded with solvent, detect mark rate, same method using TLC thin layer radioactive scanning instrument
Monitor external 2h internal stability.
It measures68The yield 92% of Ga-oxine.
Embodiment 2:
68The preparation of Ga-oxine: ITG 740MBq is eluted with the 0.05mol/L HCl of 4mL68Ge/68Ga generator, takes
The crest segment 3mL of leacheate；It takes leacheate described in wherein 500 μ L that the NaAc solution of 1mol/L is added, adjusts the pH to 5 of leacheate；
1mg oxine powder is weighed using ten a ten thousandth balances, is dissolved in 10% acetic acid solution, compound concentration is 1mg/mL's
Oxine solution mixes concussion；Leacheate and 10 μ L oxine solution are mixed at room temperature, react 60min.
TLC Quality Control: it prepares solvent (methylene chloride: methanol=9.5:0.5+1% triethylamine), carrier is glass fibre
Paper；It dries up after extracting reaction solution point sample, is unfolded with solvent, detect mark rate, same method using TLC thin layer radioactive scanning instrument
Monitor external 2h internal stability.
It measures68The yield 98% of Ga-oxine.
Embodiment 3:
The present embodiment 1 the difference from embodiment 1 is that, the pH for adjusting leacheate is respectively 3~7, remaining condition and implement
Example 1 is identical.Experimental result as shown in Figure 1, pH value for68The high yield preparation of Ga-oxine has a significant impact, by leacheate
Yield obviously increases when pH is adjusted to 5, and pH below 4 or pH be greater than 6 when,68The yield of Ga-oxine significantly reduces.
Embodiment 4:
The present embodiment 1 the difference from embodiment 1 is that, adjusting reaction time is respectively 10~120min.Experimental result is such as
Shown in Fig. 2, the reaction time is significantly affected68The yield of Ga-oxine.When reaction time 10min,68Ga-oxine yield reaches
90% or more.
Embodiment 5:
It is produced by the present invention68Ga-oxine answering in the drug for preparing the monitoring of CART cytokines and/or outcome prediction
With: take 10~50 μ Ci68Ga-oxine solution and 106A CART cell is washed three times after being incubated for 10min in room temperature PBS with PBS,
Cell viability before and after full-automatic cell calculating instrument monitoring mark, γ calculating instrument/activity measurement supernatant and intracellular radioactivity.
The research of the invention finds that68Ga-oxine can stablize in PBS solution, and unstable in CART cell culture fluid
It is fixed, thus select PBS as incubation solution.
The experimental results showed that68Ga-oxine activity is within the scope of 10~50 μ Ci, and labeled Cell viability is all larger than
90%.Illustrate the present invention68Ga-oxine small toxicity, to cellular damage very little.
68Ga-oxine imaging:
Using toy Positron Emission Tomography radiography (Micro PET) to tail vein injection68Ga marks CAR-T cell
Later NOG mouse carries out imaging monitoring, and detection time point is 2,2.5,4,5,6,9h.
Data reconstruction and processing analysis:
Micro PET visualization data is rebuild using OSEM 3D iterative method, delineates lung, spleen, liver using ASIProVM software
Equal tissues are area-of-interest, and the percentage injection dose rate (%ID/g) of mouse per gram of tissue is calculated according to following equation.
%ID/g=chooses area-of-interest radioactive substance intake (μ Ci/g)/total injection dosage (μ Ci) × 100.It is quantitative
Each tissue uptake values are analyzed, draw tendency chart using Gaphpad software.
Micro PET images (Fig. 3):68Ga-oxine and89The label CAR T cell dynamic living body Micro of Zr-oxine
PET imaging results show that after vein gives radiolabeled CART cell, radionuclide is initially concentrated mainly on lung
Portion, 10min after injection, lung's radioactive substance %ID/g uptake values be respectively as follows: 57.14 (89Zr label) and 40.26 (68Ga mark
Note)；Then gradually visible radioactive substance is dense poly- at liver and spleen, in the 6h of dynamic monitoring, pulmonary metabolism and spleen
Homing phenomena result is almost the same, 6h after injection, lungs radioactive substance intake %ID/g value be respectively as follows: 22.02 (89Zr label)
With 22.64 (68Ga label), spleen radioactive substance intake %ID/g value be respectively as follows: 7.16 (89Zr label) and 7.33 (68Ga mark
Note).
68Ga and89It is distributed in vivo after Zr label CART cell and is metabolized tendency chart and see Fig. 4.68Ga-oxine marks CART thin
Born of the same parents carry out monitored in vivo and greatly reduce the irradiation to human normal tissue and CART cell, utilize OLINDA (version number
2.1) it calculates,89It is 1.29mSv/MBq that Zr-oxine, which marks CART to carry out tracer bring internal dose,；And it utilizes68Ga-
It is only 0.05mSv/MBq that oxine, which marks CART cell to carry out monitored in vivo bring internal dose,.Simultaneously68Ga-oxine mark
Note can also realize for CAR-T early stage distribution, outcome prediction, Visual retrieval etc. research, be expected to power-assisted precisely target it is thin
The research and development of born of the same parents' class drug.
The experimental results showed that being used in the case where guaranteeing same cell motility rate > 90%68Ga-oxine is compared to adopting
With89High ten times of specific activity or more of Zr-oxine utilize68Ga marks 10^6 CART cell that 10-20 μ Ci (370- can be obtained
Radioactive activity 740KBq), and utilize89Zr 10^6 CART cell of label only obtains the radioactivity of 1-2 μ Ci (37-74KBq)
Activity.And due to89The specific activity of Zr-oxine is lower, and radioactively labelled substance can not carry out clinical conversion after being diluted.
Embodiment 6:
89The synthesis of Zr-oxine:
It is free89Zr solution 0.1M Herpes solution and sodium carbonate liquor adjust pH to 7.It is same to prepare oxine solution methods
Embodiment 1 will mix up pH's89Zr and 20 μ L oxine solution mix, and react at room temperature 15min.
The Quality Control of TLC method is the same as embodiment 1.
What 100 μ Ci were now marked89Zr-oxine solution and 106Cell washes three with PBS after room temperature PBS system is incubated for 10min
It is secondary.Full-automatic cell calculating instrument mark note front and back Cell viability.γ calculating instrument/activity measurement supernatant and intracellular radioactivity.
89Zr half-life period is 78.4h,89Zr mark CART cell infusion body in after, radioactive substance for a long time lung, liver and
The normal tissues such as spleen are dense poly-, can bring damage to tissue and CART cell,89Zr marks CAR-T cell in the feelings of high specific activity
Under condition, when being such as higher than 370-740KBq/10^6 cell, Cell viability can be significantly reduced, and can be lower than 80%.
89Zr-oxine imaging:
It is imaged using Micro PET to tail vein injection89The later NOG mouse of Zr label CAR-T cell carries out imaging prison
It surveys, detection time point is 1,4,6,17,25,30,41,51,65,75h.
Data reconstruction and processing analysis method are same as Example 5.
The present invention uses68CART cell is marked in Ga-oxine, develops a kind of new CART cytokines monitoring
And/or the drug of outcome prediction,68The irradiation to human normal tissue and CART cell can be greatly reduced in Ga-oxine, while real
The early stage distribution for CAR-T, outcome prediction are showed, the research such as Visual retrieval is expected to the cell class medicine that power-assisted precisely targets
The research and development of object.
It should be noted that the above examples are only used to illustrate the technical scheme of the present invention and are not limiting, although referring to preferable
Embodiment describes the invention in detail, those skilled in the art should understand that, it can be to technology of the invention
Scheme is modified or replaced equivalently, and without departing from the spirit and scope of the technical solution of the present invention, should all be covered in this hair
In bright scope of the claims.
Claims (10)
1. the drug of a kind of monitoring of CART cytokines and/or outcome prediction, it is characterised in that: the drug includes68Ga-
Oxine, structural formula are as follows:
2. a kind of method for the drug for preparing the monitoring of CART cytokines and/or outcome prediction, it is characterised in that: including,
740 MBq of ITG is eluted with HCl68Ge/68Ga generator, takes leacheate；
The pH that NaAc solution adjusts leacheate is added；
Oxine solution is added to mix, react, obtains68Ga-oxine。
3. the method for preparing the drug of the monitoring of CART cytokines and/or outcome prediction as claimed in claim 2, feature exist
In: the HCl is the 0.05mol/L of 4mL.
4. the method for preparing the drug of the monitoring of CART cytokines and/or outcome prediction as claimed in claim 2 or claim 3, special
Sign is: it is described to take leacheate, for the 2~3mL of leacheate for taking elution crest segment.
5. the method for preparing the drug of the monitoring of CART cytokines and/or outcome prediction as claimed in claim 2 or claim 3, special
Sign is: the pH that NaAc solution is added and adjusts leacheate, wherein the concentration of the NaAc solution is 1mol/L.
6. the method for preparing the drug of the monitoring of CART cytokines and/or outcome prediction as claimed in claim 2 or claim 3, special
Sign is: the pH that NaAc solution is added and adjusts leacheate, wherein the pH for adjusting leacheate is 5~6.
7. the method for preparing the drug of the monitoring of CART cytokines and/or outcome prediction as claimed in claim 2 or claim 3, special
Sign is: the addition oxine solution mixes, and is that oxine powder is dissolved in 10% acetic acid solution, compound concentration is
The oxine solution of 1mg/mL.
8. the method for preparing the drug of the monitoring of CART cytokines and/or outcome prediction as claimed in claim 2 or claim 3, special
Sign is: the reaction, is 37 DEG C of 10~60min of reaction.
9. according to any one of claims 1 to 868Ga-oxine is in the monitoring of preparation CART cytokines and/or outcome prediction
Drug in application, it is characterised in that: including taking 10~50 μ Ci68Ga-oxine solution and 106A CART cell is in room temperature
10min is incubated in PBS.
10. as claimed in claim 968Ga-oxine is in the drug for preparing the monitoring of CART cytokines and/or outcome prediction
Application, it is characterised in that: it is described68The CART Cell viability of Ga-oxine label is greater than 90%, for CART cell early stage point
Irradiation dose is low in body when cloth monitors, and is89The 3-5% of Zr-oxine label.
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| Application Number | Priority Date | Filing Date | Title |
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| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| CN201910602155.5A CN110283120B (en) | 2019-07-05 | 2019-07-05 | Medicine for monitoring CART cell living body and/or predicting curative effect, preparation method and application thereof |
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Cited By (1)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| CN114107191A (en) * | 2021-12-09 | 2022-03-01 | 益诺思生物技术南通有限公司 | A kind of89Method for labeling human umbilical cord mesenchymal stem cells by Zr |
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2019
- 2019-07-05 CN CN201910602155.5A patent/CN110283120B/en active Active
Cited By (2)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| CN114107191A (en) * | 2021-12-09 | 2022-03-01 | 益诺思生物技术南通有限公司 | A kind of89Method for labeling human umbilical cord mesenchymal stem cells by Zr |
| CN114107191B (en) * | 2021-12-09 | 2024-03-12 | 益诺思生物技术南通有限公司 | The method comprises the following steps of 89 Method for marking human umbilical cord mesenchymal stem cells by Zr |
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