RGD polypeptide radiopharmaceuticals and preparation method thereof

Abstract

The invention relates to an RGD polypeptide radiopharmaceutical and a preparation method thereof. The RGD polypeptide radiopharmaceutical includes an RGD polypeptide and a radionuclide<99m>Tc, wherein, the RGD polypeptide radiopharmaceutical is an RGD cyclopeptide dimmer, that is, E(L-cRGDxK)2 which is synthesized by dimerizing two RGD polypeptide monomers connected with coupling agent L. The radionuclide<99m>Tc serves to mark the RGD cyclopeptide dimmer through a bifunctional chelating agent HYNIC. A pharmacokinetics modified molecule PKM is further connected between the RGD cyclopeptide dimmer and the bifunctional chelating agent. The RGD polypeptide radiopharmaceutical is <99m>Tc-HYNIC-PKM-E(L-cRGDxK)2. The RGD polypeptide radiopharmaceutical is colorless and transparent liquid injection. The RGD polypeptide radiopharmaceutical provided by the invention has the advantages of further reinforcing the binding affinity and the ingestion of drugs by tumor, and achieving better diagnosis effect.

Description

technical field [0001] The present invention relates to tumor diagnostic radiopharmaceuticals, in particular to integrin α v beta 3 RGD polypeptide radiopharmaceutical for positive tumor diagnosis and its preparation method. Background technique [0002] A critical part of the tumor growth process is tumor angiogenesis. No new angiogenic tumors can no longer grow after reaching a size of a few centimeters. Tumor angiogenesis is regulated by various protein molecules, including integrin α v beta 3 . integrin alpha v beta 3 It is an extracellular matrix receptor, which is a heterodimeric transmembrane glycoprotein composed of α and β subunits. integrin alpha v beta 3 It is an important member of the integrin family. As one of the molecular markers related to neovascularization, it is highly expressed on the surface of neovascular endothelial cells and some tumor cells (neuroblastoma, osteosarcoma, glioblastoma , breast and prostate cancer, etc.), but no or very low ...

AI Technical Summary

Problems solved by technology

Currently reported RGD cyclic peptide dimer E[c(RGDxK)] 2 (E represents glutamic acid, c represents cyclization, R represents arginine, G represents glycine, D represents aspartic acid, x represents f or y, representing phenylalanine or tyrosine respectively), two of them The distance between RGD modules is 6 bonds, because the distance is not long enough, so E[c(RGDxK)] 2 It is difficult for the two RGD motifs of the cell surface to be adjacent to the two integrin α at the same time v beta 3 receptor binding (eg figure 1 shown)

Images