NGR polypeptide radiopharmaceutical as well as preparation method and application thereof

Abstract

The invention relates to an NGR (asparagine-glycine-arginine) polypeptide radiopharmaceutical as well as a preparation method and application thereof. The currently reported radionuclide-labeled NGR-containing sequence has a higher liver uptake rate. The NGR polypeptide radiopharmaceutical is formed with the preparation method comprising the steps as follows: monomers and dimmers of an NGR cyclopeptide are connected with a chelating agent NOTA to form a coordination compound, and the coordination compound finally forms the radiopharmaceutical through chelation of the NOTA (disodium edta) and radionuclides; the targeting action of the NGR polypeptide enables the radiopharmaceutical to be concentrated to a tumor part, and the nuclear medicine positron emission computerized tomography technology is utilized to image the CD13 positive tumor, so as to achieve the purpose of specific diagnosis. According to the invention, since the NOTA is used as a bifunctional chelator to be chelated with the radionuclides, and the p-SCN-Bn is used as a coupling agent to enable the NGR to be directly connected to a carbon skeleton of the NOTA, the situation that the coordination of the carboxyl oxygen atoms and the radionuclides is influenced by connection of the coupling agent and the NOTA carboxyl is avoided; seen from the metabolism in vivo, the radiopharmaceutical can be quickly metabolized through the kidney after being injected into the body, and the liver uptake rate is lower.

Description

technical field

[0001] The invention relates to a radiopharmaceutical for tumor diagnosis, in particular to an NGR polypeptide radiopharmaceutical and its preparation method and application. Background technique

[0002] Tumor growth and metastasis depend on the formation of new blood vessels, and without the vasculature to provide oxygen and nutrients, solid tumors will not grow beyond 1 mm 3 , blocking the formation of new blood vessels can inhibit tumor growth, resulting in tumor shrinkage and regression, using markers specifically expressed on the surface of new blood vessels such as α v beta 3 、α v beta 5 Integrin, vascular endothelial growth factor receptor VEGFR, aminopeptidase N (CD13) as targets to develop tumor-targeted therapeutic drugs is an important strategy for tumor-targeted therapy. Effective monitoring of tumor angiogenesis, screening of relevant drug-sensitive populations, and early objective evaluation of drug efficacy are clinical problems to be sol...

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