Catabolism of neurotensins - Implications for the design of radiolabeling strategies of peptides

A major impact in diagnosis and treatment of cancer with peptide based radi opharmaceuticals is expected. Among others neurotensin is considered to be a promising candidate. However, most neurotensin analogues, which bind to t he neurotensin receptor have a too short biological half live due to catabo lism. Therefore, stabilized fragments have been prepared and labeled with t he newly developed [Tc(CO)(3)](+)-moiety. A single histidine or a (N alpha- His)-Ac group coupled to the N-terminus of the neurotensin fragments were u sed as a bidentate or a tridentate ligand respectively, which coordinate th e metal carbonyl efficiently. Affinity and binding studies of the Tc-99m(I) radiolabeled neurotensin fragments revealed a behavior influenced by catab olism and properties of the metal complex.