Synthesis, biological and preclinical evaluation of (D-Phe6,Leu-NHEt13,des-Met14)bombesin(6-14) analogs modified with 1,4,8,11-tetraazaundecane derivatives and labeled with technetium-99m for application in oncology

摘要

In the present invention the synthesis of analogs of the bombesin (BBN) antagonist, (D-Phe<6>,Leu-NHEt<13>,des-Met<14>)BBN(6-14), is described, to which 1,4,8,11-tetraazaundecane derivatives have been coupled, in order to enable labeling with technetium-99m aiming at their application in the in vivo localization of BBN/GRP-positive neoplasms in the human applying SPECT (single photon emission computed tomography). In addition, the method of labeling of (D-Phe<6>,Leu-NHEt<13>,des-Met<14>)BBN(6-14) analogs, modified with 1,4,8,11-tetraazaundecane derivatives, with technetium-99m is described. This invention also includes the radiochemical evaluation of technetium-99m complexes deriving from the above steps: labeling yield, lipophilicity measurement and in vitro stability. Finally this invention describes also the preclinical evaluation of the analogs deriving from the above steps: In cell lines overesxpressing the BBN/GRP receptor in in vivo animal models and the study of their metabolism.l