Tyr3-Octreotide and Tyr3-Octreotate Radiolabeled with 177Lu or 90Y: Peptide Receptor Radionuclide Therapy Results In Vitro

Abstract

Somatostatin analogs promising for peptide receptor scintigraphy (PRS) and peptide receptor radionuclide therapy (PRRT) are D-Phe-c(Cys-Tyr-D-Trp-Lys-Thr-Cys)-Thr(ol) (Tyr3-octreotide) and D-Phe-c(Cys-Tyr-D-Trp-Lys-Thr-Cys)-Thr (Tyr3-octreotate). For radiotherapeutic applications these peptides are being labeled with the β- particle emitters 177Lu or 90Y. We evaluated the therapeutic effects of these analogs chelated with tetra-azacyclododecatatro-acetic acid (DOTA) and labeled with 90Y or 177Lu in an in vitro colony-forming assay using the rat pancreatic tumor cell line CA20948. Furthermore, we investigated the effects of incubation time, radiation dose, and specific activity of [ 177Lu-DOTA]-D-Phe1-c (Cys-Tyr-D-Trp-Lys-Thr-Cys)-Thr (177Lu-octreotate). 177Lu-octreotate could reduce tumor growth to 100% cell kill and effects were dependent on radiation dose, incubation time, and specific activity used. Similar concentrations of 177Lu-DOTA, which is not bound to the cells, had a less pronounced effect on the tumor cell survival. Both Tyr3-octreotide and Tyr 3-octreotate labeled with either 177Lu or 90Y, using DOTA as chelator, were able to control tumor growth in a dose-dependent manner. In all concentrations used radiolabeled Tyr3-octreotate had a higher tumor kill compared to radiolabeled Tyr3-octreotide, labeled with 177Lu or 90Y. This is in accordance with the higher affinity of Tyr3-octreotate for the subtype 2 (sst 2)-receptor compared to Tyr3-octreotide, leading to a higher amount of cell-associated radioactivity, resulting in a significantly higher tumor radiation dose. In conclusion, Tyr3-octreotate labeled with 177Lu or 90Y is the most promising analog for PRRT.