TRICARBONYL TECHNETIUM-99m OR RHENIUM-188 LABELED CYCLIC RGD DERIVATIVES, A PREPARATION METHOD THEREOF, AND A PHARMACEUTICAL COMPOSITION CONTAINING THE DERIVATIVES AS AN ACTIVE INGREDIENT FOR USE IN THE DIAGNOSIS OR TREATMENT OF ANGIOGENESIS-RELATED DISEASES

摘要

The present invention relates to tricarbonyl technetium-99m or rhenium-188 labeled cyclic RGD derivatives, a preparation method thereof, and a pharmaceutical composition containing the derivative as an active ingredient for use in the diagnosis or treatment (radiotherapy) of angiogenesis-related diseases. The tricarbonyl technetium-99m or rhenium-188 labeled cyclic RGD derivatives of the present invention has a high subnanomolar affinity to integrin α_vβ₃ (also called as a vitronectin receptor) that is activated in an angiogenic action induced by a tumor, reflects a high tumor image of the tricatvonyl technetium-99m labeled cyclic RGD derivative after initial intake in an animal in which cancer cells are transplanted, and acts exclusively upon cancer cells having selectively activated integrin α_vβ₃ because of a substantially low intake into the liver and intestines, compared to existing known radioactive isotope labeled cyclic RGD derivatives. These results show that the rhenium-188 labeled derivative, a therapeutic nuclide using the same precursor as used in the technetium-99m labeling, effectively inhibits the growth of a tumor and demonstrates therapeutic efficacy when administered via tail vein injection to an animal model bearing tumor, compared to a case where only saline has been injected, thereby making it useful as a medicine for the diagnosis or treatment of angiogenesis-related diseases.