title: Peptide receptor radionuclide therapy in vitro using [111In-DTPA0]octreotide.
abstract: Peptide receptor radionuclide therapy (PRRT) using [(111)In-DTPA(0)]octreotide (where DTPA is diethylenetriaminepentaacetic acid) is feasible because, besides gamma-radiation, (111)In emits both therapeutic Auger and internal conversion electrons having a tissue penetration of 0.02-10 and 200-500 micro m, respectively. The aim of this study was to investigate the therapeutic effects of [(111)In-DTPA(0)]octreotide in a single-cell model including the effects of incubation time, radiation dose, and specific activity of [(111)In-DTPA(0)]octreotide. Finally, we discriminated between the effects of the Auger electrons and internal conversion electrons in PRRT.
  
  
  METHODS
  An in vitro, colony-forming assay to study cell survival after PRRT using the sst subtype 2-positive rat pancreatic tumor cell line CA20948 was developed.
  
  
  RESULTS
  In this in vitro system [(111)In-DTPA(0)]octreotide can control tumor growth to 0% survival, and the effects were dependent on incubation time, radiation dose, and specific activity used. Similar concentrations of (111)In-DTPA, which is not internalized into sst-positive tumor cells like [(111)In-DTPA(0)]octreotide, did not influence tumor survival. Excess unlabeled octreotide (10(-6) mol/L) could decrease tumor cell survival to 60% of control; the addition of radiolabeled peptide ([(111)In-DTPA(0)]octreotide [10(-9) mol/L] + 10(-6) mol/L octreotide) did not further decrease survival.
  
  
  CONCLUSIONS
  These in vitro studies show that the therapeutic effect of (111)In is dependent on internalization, enabling the Auger electrons with their very short particle range to reach the nucleus. Our results also indicate that the PRRT effects were receptor mediated.
authors.affiliation: Department of Nuclear Medicine, Erasmus Medical Center, Rotterdam, The Netherlands. capello@nuge.azr.nl
authors.forename: Astrid
authors.initials: A
authors.lastname: Capello
authors.forename: Eric P
authors.initials: EP
authors.lastname: Krenning
authors.forename: Wout A P
authors.initials: WA
authors.lastname: Breeman
authors.forename: Bert F
authors.initials: BF
authors.lastname: Bernard
authors.forename: Marion
authors.initials: M
authors.lastname: de Jong
mesh_terms: D000818:Animals; D017209:Apoptosis / Q000528:radiation effects*; D004307:Dose-Response Relationship, Radiation; D004583:Electrons; D007205:Indium Radioisotopes / Q000627:therapeutic use*; D015282:Octreotide / Q000031:analogs & derivatives* / Q000627:therapeutic use*; D010190:Pancreatic Neoplasms / Q000532:radiotherapy*; D004369:Pentetic Acid / Q000031:analogs & derivatives* / Q000627:therapeutic use*; D019275:Radiopharmaceuticals / Q000627:therapeutic use*; D051381:Rats; D018000:Receptors, Peptide / Q000627:therapeutic use; D015203:Reproducibility of Results; D012680:Sensitivity and Specificity; D014407:Tumor Cells, Cultured
chemical_list: D007205:Indium Radioisotopes; D019275:Radiopharmaceuticals; D018000:Receptors, Peptide; C071632:SDZ 215-811; D004369:Pentetic Acid; D015282:Octreotide