Tricarbonyl Tc-99m or Re-188 labeled cyclic RGD derivatives or pharmaceutically acceptable salts thereof, preparation method thereof, and pharmaceutical composition for the diagnosis or treatment of angiogenesis-related disease containing the same as an active ingredient

摘要

The present invention relates to a tricarbonyl technetium-99m or rhenium-188 label ring RGD derivative, a preparation method thereof, and a pharmaceutical composition containing the derivative as an active ingredient for use in the diagnosis or treatment of angiogenesis-related diseases. The tricarbonyl technetium-99m or rhenium-188 label ring RGD derivative of the present invention has a high subnanomolar affinity to avss3 integrin (also called as a vitronectin receptor that is activated in an angiogenic action induced by a tumor, reflects a high tumor image after an animal in which cancer cells are transplanted received an initial intake of the tricarbonyl technetium-99m label ring RGD derivative, and acts exclusively upon cancer cells having selectively activated avss3 integrin because of a substantially low intake into the liver and intestines,; compared to existing known radioactive isotope label ring RGD derivatives. These results show that the rhenium-188 label derivative, a therapeutic nuclide using the same precursor as used in the technetium-99m label, effectively inhibits the growth of a tumor and demonstrates therapeutic efficacy when administered via tail vein injection to an animal model of a 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.