title: Somatostatin-receptor-targeted alpha-emitting 213Bi is therapeutically more effective than beta(-)-emitting 177Lu in human pancreatic adenocarcinoma cells.
abstract: BACKGROUND
  Advance clinical cancer therapy studies of patients treated with somatostatin receptor (sstr)-targeted [DOTA(0)-Tyr(3)]octreotide (DOTATOC) labeled with low-linear-energy-transfer (LET) beta(-)-emitters have shown overall response rates in the range of 15-33%. In order to improve outcomes, we sought to compare the therapeutic effectiveness of sstr-targeted high-LET alpha-emitting (213)Bi to that of low-LET beta(-)-emitting (177)Lu by determining relative biological effectiveness (RBE) using the external gamma-beam of (137)Cs as reference radiation.
  
  
  METHODS
  Sstr-expressing human pancreatic adenocarcinoma Capan-2 cells and A549 control cells were used for this study. The effects of different radiation doses of (213)Bi and (177)Lu labeled to 1,4,7,10-tetraazacyclododecane-1,4,7,10-tetraacetic acid and sstr-targeted DOTATOC were investigated with a clonogenic cell survival assay. Apoptosis was measured using the Cell Death Detection ELISA(PLUS) 10x kit.
  
  
  RESULTS
  Using equimolar DOTATOC treatment with concurrent irradiation with a (137)Cs source as reference radiation, the calculated RBE of [(213)Bi]DOTATOC was 3.4, as compared to 1.0 for [(177)Lu]DOTATOC. As measured in terms of absorbance units, [(213)Bi]DOTATOC caused a 2.3-fold-greater release of apoptosis-specific mononucleosomes and oligonucleosomes than [(177)Lu]DOTATOC at the final treatment time of 96 h (P<.001) in sstr-expressing Capan-2 cells.
  
  
  CONCLUSIONS
  In conclusion, at the same absorbed dose, [(213)Bi]DOTATOC is therapeutically more effective in decreasing survival than is [(177)Lu]DOTATOC in human pancreatic adenocarcinoma cells due to its comparatively higher RBE.
authors.affiliation: Radiopharmaceutical Sciences Program, College of Pharmacy, University of New Mexico, Albuquerque, NM 87131-0001, USA.
authors.forename: Tapan K
authors.initials: TK
authors.lastname: Nayak
authors.forename: Jeffrey P
authors.initials: JP
authors.lastname: Norenberg
authors.forename: Tamara L
authors.initials: TL
authors.lastname: Anderson
authors.forename: Eric R
authors.initials: ER
authors.lastname: Prossnitz
authors.forename: Michael G
authors.initials: MG
authors.lastname: Stabin
authors.forename: Robert W
authors.initials: RW
authors.lastname: Atcher
mesh_terms: D000230:Adenocarcinoma / Q000473:pathology / Q000532:radiotherapy*; D000512:Alpha Particles / Q000627:therapeutic use; D001610:Beta Particles / Q000627:therapeutic use; D001729:Bismuth / Q000008:administration & dosage*; D045744:Cell Line, Tumor; D049109:Cell Proliferation / Q000528:radiation effects; D002470:Cell Survival / Q000528:radiation effects; D004307:Dose-Response Relationship, Radiation; D016503:Drug Delivery Systems / Q000379:methods*; D006801:Humans; D008187:Lutetium / Q000008:administration & dosage*; D010190:Pancreatic Neoplasms / Q000473:pathology / Q000532:radiotherapy*; D011868:Radioisotopes / Q000008:administration & dosage*; D019275:Radiopharmaceuticals / Q000008:administration & dosage; D011879:Radiotherapy Dosage; D017481:Receptors, Somatostatin / Q000037:antagonists & inhibitors*; D016896:Treatment Outcome
chemical_list: D011868:Radioisotopes; D019275:Radiopharmaceuticals; D017481:Receptors, Somatostatin; D008187:Lutetium; D001729:Bismuth