Chemistry & Biology
Volume 13, Issue 10, October 2006, Pages 1081-1090
Journal home page for Chemistry & Biology

Article
Design, Synthesis, and Biological Evaluation of Somatostatin-Based Radiopeptides

https://doi.org/10.1016/j.chembiol.2006.08.012Get rights and content
Under an Elsevier user license
open archive

Summary

The prototypes for tumor targeting with radiolabeled peptides are derivatives of somatostatin. Usually, they primarily have high affinity for somatostatin receptor subtype 2 (sst2), and they have moderate affinity for sst5. We aimed at developing analogs that recognize different somatostatin receptor subtypes for internal radiotherapy in order to extend the present range of accessible tumors. We synthesized DOTA-octapeptides based on octreotide by replacing Phe3 mainly with unnatural amino acids. The affinity profile was determined by using cell lines transfected with sst1–5. Internalization was determined by using AR42J, HEK-sst3, and HEK-sst5 cell lines, and biodistribution was studied in rat tumor models. Two of the derivatives thus obtained showed an improved binding affinity profile, enhanced internalization into cells expressing sst2 and sst3, respectively, and better tumor:kidney ratios in animals.

CHEMBIO
CELLCYCLE

Cited by (0)