Synthesis of metabolically stable ~(99m)Tc-labeled neurotensin(8-13)analogs for tumour diagnosis

摘要

Since pancreas carcinoma over express neurotensin(NT)receptors,the NT(8-13)sequence(Arg-Arg-Pro-Tyr-Ile-Leu)is an attractive targeting molecule for the development of radiopharmaceuticals for diagnosis and therapy of this type of carcinoma.The retro-(N~(alpha)-carboxymethyl histidine)moiety,short(N~(alpha)His)Ac,functions as an efficient chelator for the ~(99m)Tc(CO)_3 core which allows the labeling of peptides with very high specific activity.A series of metabolically stabilized NT(8-13)analogs has been developed using a strategy based on amide bond modifications and the use of bulky side chains.The present work reports the further improvement of the pharmacokinetic properties of ~(99m)Tc-NT(8-13)analogs.