title: 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) (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.
authors: Department of Nuclear Medicine, Erasmus MC, Rotterdam, The Netherlands. a.capello@erasmusmc.nl
authors: Astrid
authors: A
authors: Capello
authors: Eric P
authors: EP
authors: Krenning
authors: Wout A P
authors: WA
authors: Breeman
authors: Bert F
authors: BF
authors: Bernard
authors: Mark W
authors: MW
authors: Konijnenberg
authors: Marion
authors: M
authors: de Jong
mesh_terms: D000818:Animals; D045744:Cell Line, Tumor; D002470:Cell Survival / Q000187:drug effects; D004305:Dose-Response Relationship, Drug; D008187:Lutetium; D015282:Octreotide / Q000031:analogs & derivatives* / Q000494:pharmacology*; D010456:Peptides, Cyclic / Q000378:metabolism / Q000494:pharmacology*; D011868:Radioisotopes; D051381:Rats; D018000:Receptors, Peptide / Q000378:metabolism*; D015019:Yttrium
chemical_list: D010456:Peptides, Cyclic; D011868:Radioisotopes; D018000:Receptors, Peptide; C470036:octreotate, Tyr(3)-; C045210:3-Tyr-octreotide; D015019:Yttrium; D008187:Lutetium; D015282:Octreotide