NGR polypeptide radiopharmaceutical as well as preparation method and application thereof
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A technology of radiopharmaceuticals and synthetic methods, which is applied in the field of NGR polypeptide radiopharmaceuticals and its preparation, can solve the problems of unclear mechanism and unexplained position of the label, etc., and achieve the effect of low liver uptake
Active Publication Date: 2014-01-01
FOURTH MILITARY MEDICAL UNIVERSITY
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99m The method of Tc labeling NGR is direct labeling, the author did not explain the location of the labeling, and the mechanism is not clear
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Embodiment 1
[0060] Example 1: 68 Preparation of Ga-NOTA-Gly3-NGR polypeptide radiopharmaceutical:
[0061] (1) Preparation of NOTA-Gly3-NGR:
[0062] Will p -SCN-Bn-NOTA (3.42 mg, 6.1 μmol) was dissolved in 25 μL dimethyl sulfoxide (DMSO), and Gly3-NGR polypeptide monomer (GGGCNGRC, 4-8 two cysteines connected to form a ring) was added ( 4.0 mg, 5.55 μmol), dissolve 20 μL of N,N-diisopropylethylamine (DIPEA) in 200 μL of N,N-dimethylformamide (DMF) solution, after reacting for 1 h, add 20 μL of acetic acid The reaction was stopped by 500 μL of the aqueous solution, and the reaction was stopped by Luna C18 (5 μm, 250 × 10 mm) semi-preparative column HPLC method (Waters HPLC, equipped with 2 515 pumps, 2487 UV detector, wavelength 214 nm and 254 nm, gradient elution 27.5 min, mobile phase A is 0.1% TFA aqueous solution, mobile phase B is 0.1% TFA acetonitrile solution, starting with 95% A, 5% B, and ending with 40% A, 60% B.) Separation Purify, collect the fractions with a retention time of a...
Embodiment 2
[0067] Example 2: 68 Preparation of Ga-NOTA-E(Gly3-NGR)2 polypeptide radiopharmaceutical:
[0068] (1) Synthesis of Boc-E(Gly3-NGR)2:
[0069] Boc-protected glutamate activated ester Boc-E(OSu)2 (2.05 mg, 4.6 μmol), Gly3-NGR peptide monomer (GGGCNGRC, 4-8 two cysteines linked to form a ring) (10.0 mg, 14 μmol) mixed and dissolved in DMF, adjusted the pH to 8-9, stirred at room temperature for 8-12 h, separated and purified by Luna C18 (5 μm, 250 × 10 mm) semi-preparative column HPLC method (same as Example 1), and collected retention time About 13 min fractions, the collected liquids were combined and lyophilized to obtain 5.1 mg; the obtained product was analyzed by ESI-MS mass spectrometry and the result was m / z C 58 H 93 N 25 O 24 S 4 [M+H] + =1652.65, the theoretical value is 1652.57. Confirmed as the expected product Boc-E(Gly3-NGR)2,
[0070] (2) Synthesis of E(Gly3-NGR)2:
[0071] Boc-E(Gly3-NGR)2 was dissolved in 0.5 ml trifluoroacetic acid:triisopropylsilane:water=95:2.5...
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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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