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Bi-modal tumor targeted nano particle photographic developer and method for preparing same

A nanoparticle, tumor targeting technology, applied in the fields of radiopharmaceutical chemistry and clinical nuclear medicine, can solve the problems of low tumor uptake, small molecular weight, difficult long-term continuous imaging, etc., achieve clear tumor imaging, reduce phagocytosis, and increase blood flow. The effect of retention time

Active Publication Date: 2014-01-01
BEIJING CANCER HOSPITAL PEKING UNIV CANCER HOSPITAL
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  • Summary
  • Abstract
  • Description
  • Claims
  • Application Information

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Problems solved by technology

However, since RGD is a cyclic tripeptide with a small molecular weight, it can be cleared quickly in the body, and the tumor uptake is relatively low, so it is difficult for long-term continuous imaging

Method used

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  • Bi-modal tumor targeted nano particle photographic developer and method for preparing same
  • Bi-modal tumor targeted nano particle photographic developer and method for preparing same
  • Bi-modal tumor targeted nano particle photographic developer and method for preparing same

Examples

Experimental program
Comparison scheme
Effect test

Embodiment 1

[0029] Example 1 Bimodal tumor targeting nanoparticle imaging agent and preparation method thereof

[0030] Bimodal tumor-targeted nanoparticle imaging agent ( 111 In-NIRF-CCPM-RGD) preparation includes the following steps:

[0031] (1) According to the molar ratio of amino groups on the surface of NIRF-CCPM to NCS-Bz-DTPA at 1:1, react for 24 hours in the dark to obtain DTPA-NIRF-CCPM; then according to the molar ratio of NIRF-CCPM nanoparticles to GMBS as 1:1 3 Mix and react for 2 hours in the dark to obtain DTPA-NIRF-CCPM-GMBS; after the reaction is completed, separate with PD-10 column. The PD-10 column is rinsed with 0.01M PBS buffer (pH 7.4) that has been demetalized and ionized before use.

[0032] (2) According to the molar ratio of DTPA-NIRF-CCPM-RGD nanoparticles and RGD-SH of 1:10, the mixture is separated by PD-10 column after the reaction is completed to obtain the tumor imaging marker precursor. Divide the nanoparticles, with N 2 After protection, seal it, distribute ...

Embodiment 2

[0035] Example 2 Bimodal tumor targeting nanoparticle imaging agent and preparation method thereof

[0036] The same preparation as in Example 1, except that the molar ratio of amino groups on the surface of NIRF-CCPM to NCS-Bz-DTPA in step (1) was changed to 1:3, and the molar ratio of NIRF-CCPM nanoparticles to GMBS was changed to 1:8. (2) The molar ratio of DTPA-NIRF-CCPM-RGD nanoparticles to RGD-SH was changed to 1:50, and the rest of the reaction conditions were the same.

[0037] The labeling rate and radiochemical purity were measured, and the results showed that the labeling rate and radiochemical purity were greater than 95%.

Embodiment 3

[0038] Example 3 Bimodal tumor targeting nanoparticle imaging agent and preparation method thereof

[0039] The same preparation as in Example 1, except that in step (1), the molar ratio of amino groups on the surface of NIRF-CCPM to NCS-Bz-DTPA was changed to 1:2, and the molar ratio of NIRF-CCPM nanoparticles to GMBS was changed to 1:4. (2) The molar ratio of DTPA-NIRF-CCPM-RGD nanoparticles to RGD-SH was changed to 1:25, and the rest of the reaction conditions were the same.

[0040] The labeling rate and radiochemical purity were measured, and the results showed that the labeling rate and radiochemical purity were greater than 95%.

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Abstract

The invention provides a bi-modal tumor targeted nano particle photographic developer and a method for preparing the bi-modal tumor targeted nano particle photographic developer. Near-Infrared fluorescence core-cross-linked polymeric micelles (NIRF-CCPM) with good biological performance serve as a carrier, coupling of polypeptide RGD (arginine-glycine-aspartic acid) with tumor targeting and nano particles is carried out to obtain a novel tumor targeting nano molecular imaging probe NIRF-CCPM-RGD, labeling is conducted on the NIRF-CCPM-RGD through a radionuclide 111In to obtain 111In-NIRF-CCPM-RGD, specific binding can be conducted on the 111In-NIRF-CCPM-RGD and an antigen alpha v beta 3 of a tumor neoangiogenesis endothelial cell, a tissue with high expression through the alpha v beta 3 is accurately positioned respectively through an infrared mode and a nuclear medicine mode to achieve tumor targeting molecule image diagnoses, and researches of a plurality of molecule image probes are conducted on the same molecule to achieve tumor early detection, early diagnosing and early treatment targets.

Description

Technical field [0001] The invention relates to the technical fields of radiopharmaceutical chemistry and clinical nuclear medicine, in particular to a bimodal tumor targeting nanoparticle imaging agent and a preparation method thereof. Background technique [0002] In the fields of radiopharmaceutical chemistry and clinical nuclear medicine technology, the continuous growth, invasion and metastasis of malignant tumors are closely related to tumor angiogenesis. In this process, integrin α v β 3 play an important role. α v β 3 It mainly works by combining with some ligands containing RGD (Arg-Gly-Asp) in the extracellular matrix (ECM). Studies have confirmed that it is highly expressed in neovascular endothelial cells, but it is rarely expressed or lacking in normal cells. Radiolabeled RGD peptide is used as a highly specific marker for nuclear medicine imaging of malignant tumors, which can achieve the purpose of early diagnosis and treatment. However, because RGD is a cyclic tr...

Claims

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Application Information

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IPC IPC(8): A61K51/08A61K49/00A61K103/20
Inventor 杨志朱华林新峰洪业
Owner BEIJING CANCER HOSPITAL PEKING UNIV CANCER HOSPITAL
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