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Single photon emission computed tomography developer and preparation method thereof

A single-photon emission and tomographic imaging technology, which is applied in the preparation method of peptides, X-ray contrast agent preparation, chemical instruments and methods, etc., can solve the problems of high preparation difficulty, low cell uptake rate, and difficult targeting

Active Publication Date: 2014-09-24
UNIV OF SCI & TECH OF CHINA
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  • Summary
  • Abstract
  • Description
  • Claims
  • Application Information

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Problems solved by technology

[0003] The purpose of the present invention is to propose a single-photon emission computed tomography imaging agent and its preparation method, in order to obtain a radioactive nano-imaging agent capable of real-time controllable self-assembly, which overcomes the high difficulty of preparation of traditional nano-imaging agents and the low cell uptake rate. It can be used to study the activity of specific enzymes in tumor cells, so that it can implement non-invasive, intuitive and rapid early diagnosis of diseases

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  • Single photon emission computed tomography developer and preparation method thereof
  • Single photon emission computed tomography developer and preparation method thereof
  • Single photon emission computed tomography developer and preparation method thereof

Examples

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Embodiment 1

[0054] Tyrosine-cysteine-arginine-arginine-valine-arginine and valine-arginine-cysteine-arginine-tyrosine were firstly synthesized by solid-phase synthesis Amino acid-arginine two peptides were synthesized separately.

[0055] The second compound X in this example 2 The synthetic route of (Acetyl-Arg-Val-Arg-Arg-Cys(StBu)-Tyr(I-125)-CBT) is as follows:

[0056]

[0057] First, the tyrosine-cysteine-arginine-arginine-valine-arginine peptide was synthesized by solid-phase synthesis, and the specific steps were as follows: 0.33 mmoles of 2-chlorotrityl After the base chloride resin was swelled in 2 ml of N,N-dimethylformamide for five minutes, 0.66 mmol of the first amino acid was added to the reactor Add 0.66 mmol N,N-diisopropylethylamine, react for two hours, react with 30 microliters of methanol for 20 minutes, cut off the first amino acid protecting group, Kaiser test shows blue, add activated 0.55 Millimoles of the second amino acid cysteine ​​reacted for two hours, ...

Embodiment 2

[0080] Embodiment 2: in vitro verification experiment

[0081] What adopted in the in vitro experiment of this embodiment is the third kind of compound X 3 At a concentration of 100 μmol / L, in a concentration of 100 mmol / L 4-hydroxyethylpiperazineethanesulfonic acid buffer, 1 mmol / L trichloroethyl phosphate, 1 mmol / L calcium chloride, and 5 μL of furin, the total volume was In 50 μL of the solution, incubate at 30°C for 16 hours to condense into dimers and self-assemble into nanoparticles.

[0082] Figure 5 The third compound X in this example is given 3 Transmission electron microscopy characterization of in vitro condensation-formed nanoparticles; Image 6 It is the third compound X in this example 3 Dynamic light scattering analysis of in vitro condensation to form nanoparticles; Figure 7 It is the third compound X in Example 2 3 UV absorption at 500-700nm before and after in vitro digestion.

[0083] in Figure 5 It is a transmission electron microscope (TEM) cha...

Embodiment 3

[0084] Embodiment 3: cell uptake experiment

[0085] Firstly, the malignant breast cancer cell line MDA-MB-468 was cultivated, and the specific operation was as follows: the malignant breast cancer cell line MDA-MB-468 was cultured in DMEM medium containing 10% bovine serum albumin by volume concentration, and the cells were cultured in a volume concentration of 5% %CO 2 Cultured in a 37°C incubator in an air environment, and the medium was changed every other day.

[0086] Then do the cell uptake experiment, the specific operation is as follows: the malignant breast cancer cell line MDA-MB-468 is planted in a six-well plate, with about 1 million cells in each well, and the volume is 1mL. 5%CO 2 After six hours of incubation in a constant temperature incubator at 37°C in an air environment, three of the wells were replaced with the second compound X containing 1 μCi 2 of fresh medium and the other three wells were replaced with 1 μCi of the sixth compound Y 2 Then collect ...

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Abstract

The invention discloses a single photon emission computed tomography developer and a preparation method thereof. The method is characterized by respectively synthetising two peptides by the solid-phase synthesis to obtain corresponding initial products and final products, synthetising a single compound with a first kind feature structure (I) or a second kind feature structure (II) and forming the developer according to a needed dosage ratio. The imaging developer is micro-molecule, good in hydrophilicity and easy to prepare, and precursor micro-molecule of the developer has peptides specially recognized by specific enzyme, so that imaging areas can be targeted actively, and controlled self-assembly of radioactive nano-structures in living cells is realized to study activity of specific enzymes in tumor cells. Compared with conventional micro-nano systems used in early disease diagnosis, by the preparation method, micro-nano materials synthetised in vitro are not needed to be injected into living bodies for tumor diagnosis, problems of low intake and difficulty in targeting of conventional nano-materials are solved.

Description

technical field [0001] The invention belongs to the technical field of nano-imaging agents, and in particular relates to a nano-imaging agent for single-photon emission computed tomography and a preparation method thereof. Background technique [0002] British "Nature" magazine biotechnology sub-journal (Nat.Biotechnol., 2004, Vol.22 (8), P.969) discloses a quantum dot nano-imaging agent and its preparation method for biological imaging, although this The imaging agent has a good imaging effect and can resist photobleaching. However, to prepare the imaging agent, it is first necessary to synthesize semiconductor nano-quantum dots, and then not only modify the polyethylene glycol fragment to improve the metabolic cycle, but also modify the target-specific Therefore, it is more difficult to prepare antibodies that recognize sex, and because the heavy metals contained in this type of quantum dot itself can cause toxicity, it also limits the development of this type of nano-imag...

Claims

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Application Information

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Patent Type & Authority Patents(China)
IPC IPC(8): C07K7/06C07K1/06C07K1/04A61K49/04
Inventor 梁高林苗庆庆
Owner UNIV OF SCI & TECH OF CHINA
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