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Tyr3-octreotide and Tyr3-octreotate radiolabeled with 177Lu or 90Y: peptide receptor radionuclide therapy results in vitro. | LitMetric

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) (Tyr 3-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 beta(-) 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 tyr3-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 (sst2)-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.

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http://dx.doi.org/10.1089/108497803770418300DOI Listing

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