| 摘要 |
The present invention refers to a novel radiopharmaceutical of Technetium-99m-N2S2-Tat(49-57-c(RGDyK) with internalization into the core of cancer cells as a potential agent for the image and therapy of tumors expressing integrins a(v)ß(3) by techniques of molecular nuclear medicine. The Tat(49-57) peptide is conjugated to the amino acid sequence Gly-Gly-Cys(Acm)-Gly-Cys(Acm)-NH2 for producing a peptide of the Tat(49-57)-N2S2-type, (E1 N2S2 is the chelation site of the peptide for being complexed to 99mTc). On the other hand, the peptide c(RGDyK), specifically recognized by integrins a(v)ß(3) and a(v)ß(5), is conjugated to the MPA group and the site Lys-MPA being used as a bond position for forming thioether with the Cys12 of the chain of the penetrating peptide Tat(49-57)- spacer ûN2S2. This novel radiopharmaceutical is a hybrid since it comprises two peptides with different biological activity in a single radio marked molecule: a peptide (Tat(49-57) for internalizing the radionuclid e intended to emit the Auger electrons and gamma radiation (Technetium-99m) into the cellular core and other peptide (RGD) that specifically recognizes the integrins a(v)ß(3) over-expressed in the neovasculature of the tumor and in tumorous cells of osteosarcoma, neuroblastoma, glioblastoma, melanoma, lung carcinoma and breast cancer. There has no report of other radiopharmaceutical based on the RGD peptide which is internalized into the core of the cancer cells. |
