title: Radiation induces up-regulation of somatostatin receptors 1, 2, and 5 in small cell lung cancer in vitro also at low absorbed doses.
abstract: BACKGROUND
  Radiation can be used to up-regulate the expression of the somatostatin receptor (sstr) subtype 2 in small cell lung cancer (SCLC) cells at absorbed doses of 2-8 Gy. Increased sstr expression results in increased binding of radiolabeled somatostatin analogs to the tumor cell, which enhances the efficacy of systemic radionuclide therapy. The aim of this study was to determine if lower absorbed doses could up-regulate sstr2 expression, and possibly influence other sstr subtypes.
  
  
  METHODS
  Human H69 SCLC cells were irradiated with an absorbed dose of 0.12-6.0 Gy and the sstr mRNA expression 3 days after irradiation was measured by quantitative real-time polymerase chain reaction for sstr1-5. At the same time point was the binding of [(177)Lu]-DOTA(0)-Tyr(3)-octreotate to the cells measured after irradiation to an absorbed dose of 0.12-2.0 Gy and compared to the binding to nonirradiated cells.
  
  
  RESULTS
  mRNA expression of sstr1, sstr2, and sstr5 was increased by a factor of 1.5-2 in cells irradiated with absorbed doses≥4 Gy and the binding of [(177)Lu]-DOTA(0)-Tyr(3)-octreotate was, accordingly, 2-3 times higher to irradiated cells for all absorbed doses, except 0.25 Gy.
  
  
  CONCLUSIONS
  The binding of [(177)Lu]-DOTA(0)-Tyr(3)-octreotate was increased after radiation exposure. This increase was observed at low absorbed doses in parallel with up-regulation of sstr1, sstr2, and sstr5 mRNA.
authors: Department of Radiation Physics, University of Gothenburg, Sahlgrenska University Hospital, Gothenburg, Sweden. jenny.oddstig@skane.se
authors: Jenny
authors: J
authors: Oddstig
authors: Peter
authors: P
authors: Bernhardt
authors: Ola
authors: O
authors: Nilsson
authors: Håkan
authors: H
authors: Ahlman
authors: Eva
authors: E
authors: Forssell-Aronsson
mesh_terms: D045744:Cell Line, Tumor; D056831:Coordination Complexes / Q000494:pharmacology*; D006801:Humans; D008175:Lung Neoplasms / Q000235:genetics* / Q000378:metabolism / Q000532:radiotherapy*; D015282:Octreotide / Q000031:analogs & derivatives* / Q000494:pharmacology; D012333:RNA, Messenger / Q000096:biosynthesis / Q000235:genetics; D019275:Radiopharmaceuticals / Q000494:pharmacology; D011880:Radiotherapy Planning, Computer-Assisted / Q000379:methods; D017481:Receptors, Somatostatin / Q000096:biosynthesis / Q000235:genetics* / Q000378:metabolism; D055752:Small Cell Lung Carcinoma / Q000235:genetics* / Q000378:metabolism / Q000532:radiotherapy*; D015854:Up-Regulation / Q000528:radiation effects
chemical_list: C572954:111indium-DOTA, Tyr(3)-octreotate; C504257:177Lu-octreotide, DOTA(0)-Tyr(3)-; D056831:Coordination Complexes; D012333:RNA, Messenger; D019275:Radiopharmaceuticals; D017481:Receptors, Somatostatin; C101130:somatostatin receptor type 1; C094573:somatostatin receptor 5; C093733:somatostatin receptor 2; D015282:Octreotide