Polyaspartic acid grafted dopamine and ethanolamine polymer chelated iron oxide nanoparticles and their radionuclide labeling

Abstract

The invention discloses a polyaspartic acid-grafted dopamine and ethanolamine polymer chelated iron oxide nanoparticle and a nuclide marker thereof. The iron oxide nanoparticle uses a polyaspartic acid-dopamine / ethanolamine grafted polymer as a ligand, and Fe 2+ and Fe 3+ As an iron source precursor, it is synthesized in one step by a continuous flow device co-precipitation method and then used 64 Cu 2+ Radioactive labeling is performed to obtain a radionuclide marker, which can be used as a PET / MRI dual-mode contrast agent.

Description

Technical Field

[0001] The invention belongs to the technical field of medical diagnostic materials, and specifically relates to polyaspartic acid grafted dopamine and ethanolamine polymer chelated iron oxide nanoparticles and nuclide markers thereof. Background Art

[0002] So far, various medical imaging technologies have been widely developed, but each technology has certain limitations and cannot provide comprehensive information to achieve accurate diagnosis of diseases. In recent years, people have been promoting non-invasive imaging methods and multimodal imaging methods that can provide more detailed images. Although imaging technology continues to advance, its visualization of the human body is still limited.

[0003] PET / MRI dual-modality imaging is a technology that integrates anatomical, functional and metabolic imaging. It has the advantages of multimodality imaging, reduced radiation exposure, spatial and temporal alignment, complementary information, etc. The use of contrast agents can greatly improve the diagnostic sensitivity and efficiency of the examination technology. Therefore, PET / MRI dual-modality contrast agents are also extremely important.

[0004] The use of dual-modal contrast agents (DMCA) can greatly improve sensitivity and contrast, and increase diagnostic efficiency. With the development of nanotechnology, the inherent physical and chemical properties of magnetic nanoparticles, such as magnetic properties, small particle size, large specific surface area, and easy surface functionalization, can achieve long-term circulation and tumor accumulation in the body, making it widely studied to integrate imaging modes in nanomedicine systems to achieve accurate diagnosis. Iron oxide nanomaterials are considered to be an ideal MRI tracer due to their excellent magnetic properties and easy binding to targeting ligands. The surface modification of the magnetic core with hydrophilic materials makes the nanoparticles suitable for biological systems. Furthermore, iron oxide nanomaterials labeled with radionuclides have the potential to be used as nuclear medicine / magnetic resonance dual-modal molecular imaging probes.

[0005] In order to obtain the PET / MRI dual-mode contrast agent, stable and monodisperse iron oxide nanoparticles are first synthesized. Nanoparticles with good dispersion can be obtained by surface ligand chelation. Biocompatible organic polymer materials are widely used as stabilizers for nanoparticles, typically polyethylene glycol (PEG), polyacrylic acid (PAA), polylactic acid (PLA), chitosan, etc. 64 Cu 2+ The nanoparticles are labeled to obtain PET / MRI dual-modality contrast agents.

[0006] At present, there are various stabilizers for nanoparticles. CN111607094A discloses a polyaspartic acid-dopamine / polyethylene glycol polymer and its use in preparing contrast agents. The polymer is grafted with polyethylene glycol to improve material stability and biocompatibility. However, due to the large molecular weight of polyethylene glycol, it is easy to synthesize agglomerated iron oxide nanoparticles rather than monodisperse particles. r 1 Only 6.78mM -1 s -1 , obviously lower.

[0007] CN116217944A discloses an amphiphilic polymer of polyaspartic acid grafted with oleylamine and its application. The polymer is a polyaspartic acid-dopamine / oleylamine / polyethylene glycol grafted copolymer, which is an amphiphilic polymer of polyaspartic acid grafted with oleylamine. It can form common micelles to encapsulate hydrophobic iron oxide nanoparticles. The nanomicelles are of multiple encapsulation types (one nanoparticle contains multiple iron oxide nanocrystals). Its T2 relaxation is very high, up to 84.5mM at 3.0T. -1 s -1 , but its T1 relaxation effect is suppressed, so it can only be used as a T2 contrast agent.

[0008] Currently, the clinical application of T 1 Contrast agents are mainly gadolinium. In recent years, it has been found that gadolinium can cause nephrogenic systemic fibrosis and residual risks in the brain.

[0009] To date, a variety of radiolabeling methods have been developed, which can generally be divided into two categories: one is to bind the radionuclide into the lattice of the nanocrystal core (intrinsic radiolabeling), and the other is to couple the radionuclide to the particle surface through a secondary chelating part or a specific part of the surface cap ligand (extrinsic radiolabeling). CA3041931 (A1) discloses a method that does not require a chelating agent or complexing agent to bind the radionuclide. 64Cu, which is directly doped into the lattice of USPIO nanoparticles, has high radiolabeling stability. However, this labeling method usually requires long radiolabeling times and high reaction temperatures in order to complete radiolabeling or improve radiolabeling yields, which is not feasible when introducing radionuclides with short half-lives and bioactive molecules. In addition, since strict radiation protection is required throughout the synthesis and purification process, radiolabeling of USPIO by intrinsic radiolabeling becomes more complicated experimentally. In contrast, exogenous (external) radiolabeling can achieve rapid labeling under mild conditions through secondary chelating groups of ligands anchored on the surface of the particles. However, how to effectively avoid the shedding of radionuclides from nanoparticles, which can lead to inaccurate diagnostic results, therefore, it remains a challenge to obtain a stable iron oxide nanoparticle labeled with radionuclides. Summary of the invention

[0010] The purpose of the present invention is to provide a polyaspartic acid grafted dopamine and ethanolamine polymer chelated iron oxide nanoparticles and fast nuclides thereof 64 Cu 2+ Marker. The radionuclide marker is a radioactive magnetic nanoparticle used as an image-enhanced PET (positron emission tomography) / MRI (magnetic resonance imaging) dual-modality contrast agent.

[0011] To achieve the purpose of the present invention, the following technical solutions are provided.

[0012] In one embodiment, a polyaspartic acid grafted dopamine and ethanolamine polymer chelated iron oxide nanoparticles of the present invention has a structure shown in Formula I,

[0013]

[0014] Ⅰ

[0015] In formula I, x is 1 to 500, and y and z are independently 0 to 500.

[0016] In another embodiment, a radioactive magnetic nanoparticle of the present invention comprises a polyaspartic acid grafted dopamine and ethanolamine polymer as shown in Formula I, iron oxide nanoparticles, and a nuclide for labeling the nanoparticles. 64 Cu 2+ , the polymer represented by the formula I chelates the iron oxide nanoparticles, and then uses the nuclide 64 Cu 2+ Obtained by rapid radionuclide labeling on the surface of nanoparticles.

[0017] In another embodiment, the present invention provides a method for preparing polyaspartic acid grafted dopamine and ethanolamine polymer chelated iron oxide nanoparticles using continuous flow, comprising the following steps:

[0018] 1) The alkali and iron precursor solutions are pumped in with a high-pressure syringe and reacted in the first T-type mixer after preheating;

[0019] 2) After quenching, the reaction product is mixed with the pumped polyaspartic acid-dopamine / ethanolamine grafted polymer in the second T-type mixer for reaction;

[0020] 3) After aging, the outflow product solution is placed in a dialysis bag for dialyzation, and the solution in the dialysis bag is collected, filtered through a membrane, and concentrated by ultrafiltration to obtain uniform and stable polyaspartic acid-dopamine / ethanolamine grafted polymer chelated iron oxide nanoparticles (SPIO@PDAEA).

[0021] Preferably, in the above-mentioned method for grafting polymer to chelate iron oxide nanoparticles, in step 1), the alkali and iron precursor solution are pumped in at a flow rate of 5 ml / min, the alkali is tetraethylammonium hydroxide solution, and the iron precursor is Fe 2+ and Fe 3+ of mixed solution.

[0022] Preferably, in the above method of grafting polymer to chelate iron oxide nanoparticles, in step 1), the reaction temperature is 60° C. and the reaction time is 60 s.

[0023] Preferably, in the above method for chelating iron oxide nanoparticles with a grafted polymer, in step 2), the flow rate of pumping the grafted polymer is 2.5 ml / min, the reaction temperature is 60° C., and the reaction time is 2 min.

[0024] In another aspect, the present invention provides a method for preparing radioactive magnetic nanoparticles, comprising the following steps:

[0025] 1) Dissolve the polyaspartic acid-dopamine / ethanolamine grafted polymer chelated iron oxide nanoparticles (SPIO@PDAEA) in sodium acetate solution and fully dissolve;

[0026] 2) Add an equal volume of 64 Cu(OAc) 2 solution, incubated under stirring and heating;

[0027] 3) After the reaction is completed, purification is performed to obtain polyaspartic acid-dopamine / ethanolamine grafted polymer chelated iron oxide nanoparticles. 64 Cu 2+ Radionuclide markers.

[0028] Preferably, in the preparation method of the radioactive magnetic nanoparticles of the present invention, the mass volume ratio of iron in the SPIO@PDAEA solid to the sodium acetate solution in step 1) is 1 mg: 250 ul.

[0029] Preferably, in the preparation method of the radioactive magnetic nanoparticles of the present invention, the nuclide in step 2) 64 Cu(OAc) 2 The activity mass ratio of iron in step 1) is 2mCi:1mg.

[0030] Preferably, in the preparation method of the radioactive magnetic nanoparticles of the present invention, in step 2), the heating temperature is 30°C-60°C, more preferably 60°C, and the incubation time is 10-30 min, more preferably 30 min.

[0031] The polyaspartic acid-dopamine / ethanolamine graft polymer of formula I of the present invention is:

[0032]

[0033] Ⅰ

[0034] In formula II, x is 1 to 500, and y and z are independently 0 to 500.

[0035] In one embodiment, a method for preparing a polyaspartic acid-dopamine / ethanolamine graft polymer of formula I comprises:

[0036] 1) Place polysuccinimide in a reaction bottle and add dimethyl sulfoxide to dissolve it;

[0037] 2) Dissolve dopamine hydrochloride with dimethyl sulfoxide and triethylamine, add the mixture into the reaction bottle under nitrogen protection and react for a period of time;

[0038] 3) Then add ethanolamine, dropwise add it into the reaction bottle under nitrogen protection, react for a period of time, and lyophilize the product after purification for later use.

[0039]

[0040] Ⅰ

[0041] In formula I, x is 1 to 500, and y and z are independently 0 to 500.

[0042] In another embodiment, the present invention provides a method for preparing a polyaspartic acid-dopamine / ethanolamine grafted polymer of formula I, comprising:

[0043] 1) Place polysuccinimide in a reaction bottle and add dimethyl sulfoxide to dissolve it;

[0044] 2) Dissolve dopamine hydrochloride with dimethyl sulfoxide and triethylamine, add to the reaction bottle under nitrogen protection, and react at 60°C for 24 hours;

[0045] 3) Then add ethanolamine and drip it into the reaction bottle under nitrogen protection, react at 40℃ for 12h, and freeze the product after purification.

[0046] In another embodiment, a method for preparing iron oxide nanoparticles coated with a graft polymer of formula I of the present invention comprises:

[0047] 1) A high-pressure syringe pumps the alkali and iron precursor solutions into the first T-type mixer;

[0048] 2) after a quenching time, rapidly mixing with the graft compound represented by formula I in a second T-type mixer;

[0049] 3) After a certain distance of aging, uniform and stable polyaspartic acid-dopamine / ethanolamine grafted polymer chelated iron oxide nanoparticles (SPIO@PDAEA) were obtained;

[0050] 4) Place the product solution in a dialysis bag for dialyzing, collect the solution in the dialysis bag, filter the membrane, concentrate by ultrafiltration, and store the solution for later use.

[0051] In one embodiment, the present invention is a superparamagnetic nanoparticle (SPIO@PDAEA) coated with a grafted polymer represented by Formula I. 64 Cu 2+ Radionuclide labeled.

[0052] Specifically, the present invention provides a SPIO@PDAEA 64 Cu 2+ Marking methods include:

[0053] 1) SPIO@PDAEA is dissolved in sodium acetate solution and fully dissolved to obtain SPIO@PDAEA solution;

[0054] 2) Add an equal volume of 64 Cu(OAc) 2 , incubate at 60°C with stirring for 30 min;

[0055] 3) After the reaction is completed, purification is performed to obtain SPIO@PDAEA- 64 Cu 2+ .

[0056] The polyaspartic acid-dopamine / ethanolamine grafted polymer chelated iron oxide nanoparticles of the present invention: 64 Cu 2+Radionuclide markers are used as image-enhanced PET (positron emission tomography) / MRI (magnetic resonance imaging) dual-modality contrast agents.

[0057] The preparation method of the present invention comprises chelating iron oxide nanoparticles with polyaspartic acid-dopamine / ethanolamine grafted polymer, and then performing 64Cu 2+ Preparation of radioactive magnetic nanoparticles (SPIO@PDAEA- 64 Cu 2+ ), the magnetic nanoparticles are used as PET / MRI dual-modality contrast agents.

[0058] The radioactive magnetic nanoparticles (SPIO@PDAEA- 64 Cu 2+ ) has an r1 of 12.8mM-1s-1, which is nearly twice the r1 of the prior art CN111607094A. Furthermore, ethanolamine has good biocompatibility and is less irritating to the skin and mucous membranes, so it has a wider range of applications in the fields of medicine and cosmetics. Although polyethylene glycol is also used in medicine and cosmetics, it can cause allergic reactions in some people. Therefore, the SPIO@PDAEA- 64 Cu 2+ It not only shows obvious advantages in r1, but also has advantages over the prior art CN111607094A in terms of biocompatibility.

[0059] The polyaspartic acid-dopamine / ethanolamine grafted polymer chelated iron oxide nanoparticles of the present invention are single-encapsulation type (one iron oxide nanocrystal is encapsulated in one nanoparticle), and its relaxation efficiency is related to the particle size of the iron oxide nanocrystal. Its T1 and T2 relaxation rates are r 1 = 12.8 mM -1 s -1 , r 2 =36.5 mM -1 s -1 , r 2 / r 1 =2.85 (0.5T), it has good T1 and T2 enhancement effects under clinical 0.5T, 1.5T and 3.0T magnetic resonance, so it can be used as a T1-T2 dual-function contrast agent for magnetic resonance. The SPIO@PDAEA nanoparticles of the present invention can be used as T1-T2 dual-function contrast agents. Compared with the multi-encapsulated iron oxide nanoparticles of CN116217944A, which can only be used as T2 contrast agents, they have a wider range of uses in imaging and better imaging effects. On the other hand, SPIO@PDAEA is 64 Cu 2+Rapid labeling, with a labeling efficiency of up to 85% and a radiochemical purity of up to 95%, can be used as an excellent PET / MRI dual-modality contrast agent. BRIEF DESCRIPTION OF THE DRAWINGS

[0060] Figure 1 It is a schematic structural diagram of the polyaspartic acid-dopamine / ethanolamine grafted polymer chelated iron oxide nanoparticles of the present invention;

[0061] Figure 2 For the present invention 64 Cu 2+ Schematic diagram of the structure of radionuclide-labeled polyaspartic acid-dopamine / ethanolamine grafted polymer chelated iron oxide nanoparticles;

[0062] Figure 3 1H-NMR spectrum of the polyaspartic acid-dopamine / ethanolamine grafted polymer of Example 1;

[0063] Figure 4 It is a schematic diagram of continuous flow reaction equipment and process;

[0064] Figure 5 The dynamic light scattering particle size distribution of the polyaspartic acid grafted dopamine and ethanolamine polymer chelated iron oxide nanoparticles of Example 2;

[0065] Figure 6 is the zeta potential of the polyaspartic acid grafted dopamine and ethanolamine polymer chelated iron oxide nanoparticles of Example 2;

[0066] Figure 7 The XRD pattern of the polyaspartic acid grafted dopamine and ethanolamine polymer chelated iron oxide nanoparticles of Example 2;

[0067] Figure 8 is a transmission electron microscopy image of polyaspartic acid grafted dopamine and ethanolamine polymer chelated iron oxide nanoparticles of Example 2;

[0068] Fig. 9 The T1 and T2 relaxation efficiencies of the polyaspartic acid grafted dopamine and ethanolamine polymer chelated iron oxide nanoparticles of Example 2 at 0.5, 1.5, and 3.0 T;

[0069] Fig.10 The T1 and T2 weighted imaging effects of different concentrations of aqueous solutions of polyaspartic acid grafted dopamine and ethanolamine polymer chelated iron oxide nanoparticles in Example 2 at 3.0T;

[0070] Fig.11 SPIO@PDAEA of Example 3 64 Cu 2+ TLC spectrum after radionuclide labeling. DETAILED DESCRIPTION

[0071] The following examples are merely representative and are used to further understand the spirit of the present invention, but are not intended to limit the scope of the present invention.

[0072] The polyaspartic acid-dopamine / ethanolamine grafted polymer chelated iron oxide nanoparticles and the 64 Cu 2+ The schematic diagram of the structure of the radionuclide marker is shown in Figure 1 and Figure 2 .

[0073] Example 1 Synthesis of polyaspartic acid-dopamine / ethanolamine grafted polymer

[0074] Preparation process:

[0075] 0.1mmol polysuccinimide was placed in a reaction bottle, and 6ml dimethyl sulfoxide was added to dissolve it; 2mmol dopamine hydrochloride was dissolved with 2ml dimethyl sulfoxide and 3mmol triethylamine, and added to the reaction bottle under nitrogen protection, and reacted at 60℃ for 24h; then 8mmol ethanolamine was added, and dripped into the reaction bottle under nitrogen protection, and reacted at 40℃ for 12h. The product was fully washed with ethanol, and dissolved in water. The solution was placed in a dialysis bag with a molecular weight cutoff of 1000Da-3500Da, and dialyzed for 24 hours. The solution in the dialysis bag was collected and lyophilized to obtain the target product. The reaction product was characterized by hydrogen nuclear magnetic resonance, such as Figure 3 The target product polyaspartic acid-dopamine / ethanolamine polymer has an average molecular weight of about 10,000 Da, which is much smaller than the polymer in the prior art CN111607094A, which has an average molecular weight of about 15,000 Da.

[0076] Example 2 Continuous batch synthesis of polyaspartic acid-dopamine / ethanolamine grafted polymer chelated iron oxide nanoparticles

[0077] Liquid continuous reaction device used for continuous flow reaction see Figure 4 .

[0078] Preparation process:

[0079] Use a fluid continuous reaction device with an inner diameter of 0.5 mm throughout the tube, and place the tube in a 60°C water bath;

[0080] A 0.5 M tetraethylammonium hydroxide solution and a 0.1 M mixed solution of ferrous sulfate heptahydrate and ferric chloride hexahydrate (Fe 2+ :Fe 3+The molar ratio was 1:2) and pumped in at a flow rate of 5 ml / min. After 60 seconds of preheating, it reached the first T-type mixer. After the reaction was completed, it was quenched for 2 seconds and quickly mixed with 0.14 M of the polymer (ligand) prepared in Example 1 in the second T-type mixer. The ligand was pumped in at a flow rate of 2.5 ml / min. After the reaction was completed, it was aged for 120 seconds to obtain a uniform and stable product SPIO@PDAEA.

[0081] SPIO@PDAEA structural characterization and property determination:

[0082] The product solution obtained in the previous step was placed in a 8k-14k Da dialysis bag, and the aqueous solution was dialyzed for 24 hours; the solution in the dialysis bag was collected, filtered through a membrane, and concentrated by ultrafiltration, and the solution was stored at 4°C.

[0083] The iron concentration in the solution was determined by atomic absorption, and the particle size and particle size distribution of the nanoparticles were determined by dynamic light scattering. Figure 5 Dynamic light scattering particle size distribution of nanoparticles, the average particle size is 22.4±6.1nm.

[0084] The ζ potential of the obtained polyaspartic acid-dopamine / ethanolamine grafted polymer chelated iron oxide SPIO@PDAEA nanoparticles was measured. The results are shown in Figure 6 .

[0085] The prepared SPIO@PDAEA nanoparticles were tested by X-ray powder diffraction (Cu target), and the results are shown in Figure 7 .

[0086] Transmission electron microscopy of SPIO@PDAEA nanoparticles showed that they were monodispersed nanoparticles, such as Figure 8 As shown, it has better imaging applications compared with the prior art CN111607094A.

[0087] The SPIO@PDAEA nanoparticle solutions were prepared into solutions with different iron concentrations of 0.02489, 0.04978, 0.09957, 0.20052, 0.29732, and 0.40103 mM, respectively. The T values ​​of each sample were measured on a 0.5, 1.5, and 3.0 T magnetic resonance relaxation efficiency instrument. 1 and T 2 Relaxation time, calculate T 1 and T 2 Relaxation efficiency (r 1 and r 2 ),like Fig. 9 As shown, the relaxation efficiency of the nanoparticles at 0.5 T is: r 1 =12.8 mM -1 s -1 ,r 2 =36.5 mM -1 s -1 , r 2 / r 1 =2.85. Fig.10 The 3.0T in vitro imaging results shown in the figure show that the nanoparticles have good T 1 and T 2 Enhanced effect (T 1 Improve MRI signal in weighted imaging, T 2 The nanoparticles of the present invention can be used for magnetic resonance imaging (MRI). 1 -T 2 Dual-function contrast agent, compared with the currently used T 1 Compared with contrast agents (gadolinium agents): ① There is no risk of nephrogenic systemic fibrosis and residual gadolinium in the body; ② The materials used are iron oxide nanocrystals, polyaspartic acid, dopamine and polyethylene glycol, all of which are biocompatible materials with high biosafety; ③ High T 1 Relaxation efficiency, and as a nano-contrast agent, it has a longer blood half-life and imaging time window; ④T 1 -T 2 Dual-functional nanocontrast agents can provide more complete multimodal cross-corroboration information in magnetic resonance imaging.

[0088] Example 3 Polyaspartic acid-dopamine / ethanolamine grafted polymer chelated iron oxide nanoparticles 64 Cu 2+ Nuclide labeling

[0089] Preparation method:

[0090] SPIO@PDAEA containing 1 mg Fe was dissolved in 250 ul sodium acetate solution and fully dissolved; an equal volume of 2 mCi 64 Cu(OAc) 2 , incubated at 60°C with stirring for 30 min; after the reaction, purified with a PD-10 desalting column, and analyzed for radiochemical purity by thin layer chromatography. Fig.11 The results show that SPIO@PDAEA can achieve rapid 64 Cu 2+ The labeling efficiency is as high as 85%, and the TLC results show that its radiochemical purity is as high as 95%. The radioactive magnetic nanoparticles finally obtained can be used as excellent PET / MRI dual-modality contrast agents and have clinical application potential.

[0091] The above embodiments are only typical, and any simple modifications and adaptations made within the spirit and essence of the present invention fall within the protection scope of the present invention.

Claims

1. A radioactive magnetic nanoparticle comprising a polyaspartic acid-dopamine / ethanolamine grafted polymer as shown in formula I, iron oxide nanoparticles, and iron oxide nanoparticles chelated by a polyaspartic acid-dopamine / ethanolamine grafted polymer as shown in formula I, and then 64 Cu 2+ Rapid radionuclide labeling of nanoparticles. Ⅰ In formula I, x is 1 to 500, y and z are independently 0 to 500, The specific preparation method comprises the following steps: Step A: preparing polyaspartic acid-dopamine / ethanolamine grafted polymer chelated iron oxide nanoparticles shown in formula I by continuous flow, comprising the following steps: 1) The alkali and iron precursor solutions are pumped in with a high-pressure syringe and reacted in the first T-type mixer after preheating; 2) After quenching, the reaction product is mixed with the pumped polyaspartic acid-dopamine / ethanolamine grafted polymer in the second T-type mixer for reaction; 3) After aging, the outflow product solution is placed in a dialysis bag for dialysis, the solution in the dialysis bag is collected, filtered through a membrane, and ultrafiltered and concentrated to obtain uniform and stable polyaspartic acid-dopamine / ethanolamine grafted polymer chelated iron oxide nanoparticles SPIO@PDAEA. Wherein, in step 1), the pumping flow rate of the alkali and iron precursor solution is 5 ml / min, and in step 2), the pumping flow rate of the polyaspartic acid-dopamine / ethanolamine grafted polymer is 2.5 ml / min; Step B: Preparation of radioactive magnetic nanoparticles, comprising the following steps: 1) dissolving the polyaspartic acid-dopamine / ethanolamine grafted polymer chelated iron oxide nanoparticles SPIO@PDAEA prepared in step A in a sodium acetate solution and fully dissolving; 2) Add an equal volume of 64 Cu(OAc)2 solution, incubated under stirring and heating; 3) After the reaction is completed, purification is performed to obtain polyaspartic acid-dopamine / ethanolamine grafted polymer chelated iron oxide nanoparticles. 64 Cu 2+ Radionuclide markers, Wherein, the preparation method of the polyaspartic acid-dopamine / ethanolamine grafted polymer shown in formula I comprises the following steps: 1) Place polysuccinimide in a reaction bottle and add dimethyl sulfoxide to dissolve it; 2) Dissolve dopamine hydrochloride with dimethyl sulfoxide and triethylamine, add the mixture into the reaction bottle under nitrogen protection and react for a period of time; 3) Then add ethanolamine, dropwise add it into the reaction bottle under nitrogen protection, react for a period of time, and lyophilize the product after purification for later use.

2. The radioactive magnetic nanoparticles according to claim 1, wherein in step A 1), the base is tetraethylammonium hydroxide solution, and the iron precursor is Fe 2+ and Fe 3+ of mixed solution.

3. The radioactive magnetic nanoparticles as claimed in claim 1, wherein in step A 1), the reaction temperature is 60°C and the reaction time is 60 seconds.

4. The radioactive magnetic nanoparticles as claimed in claim 1, wherein in step A 2), the reaction temperature is 60°C and the reaction time is 2 min.

5. The radioactive magnetic nanoparticles as claimed in claim 1, wherein the mass volume ratio of iron in the SPIO@PDAEA solid to the sodium acetate solution in step B 1) is 1 mg: (200-250 μl).

6. The radioactive magnetic nanoparticles as claimed in claim 1, wherein the nuclide in step B 2) 64 The activity mass ratio of Cu(OAc)2 to the iron in step B 1) is 2 mCi:1 mg.

7. The radioactive magnetic nanoparticles as claimed in claim 1, wherein in step B 2), the heating temperature is 30°C-60°C and the incubation time is 10-30 min.

8. The radioactive magnetic nanoparticles according to claim 7, wherein the heating temperature is 60°C and the incubation time is 30 minutes.

9. A method for preparing polyaspartic acid-dopamine / ethanolamine grafted polymer chelated iron oxide nanoparticles using continuous flow, comprising the following steps: 1) The alkali and iron precursor solutions are pumped in with a high-pressure syringe and reacted in the first T-type mixer after preheating; 2) After quenching, the reaction product is mixed with the pumped polyaspartic acid-dopamine / ethanolamine grafted polymer in the second T-type mixer for reaction; 3) After aging, the outflow product solution is placed in a dialysis bag for dialysis, the solution in the dialysis bag is collected, filtered through a membrane, and ultrafiltered and concentrated to obtain uniform and stable polyaspartic acid-dopamine / ethanolamine grafted polymer chelated iron oxide nanoparticles SPIO@PDAEA. in, In step 1), the alkali and iron precursor solution are pumped in at a flow rate of 5 ml / min, the alkali is tetraethylammonium hydroxide solution, and the iron precursor is Fe 2+ and Fe 3+ The reaction temperature is 60°C and the reaction time is 60s. In step 2), the flow rate of pumping in the polyaspartic acid-dopamine / ethanolamine grafted polymer is 2.5 ml / min, the reaction temperature is 60° C., and the reaction time is 2 min.

10. Use of the radioactive magnetic nanoparticles of claim 1 in the manufacture of a PET / MRI dual-modality contrast agent for image enhancement.

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