INTRODUCTION: 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.
INTRODUCTION: 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 humanpancreatic 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 humanpancreatic adenocarcinoma cells due to its comparatively higher RBE.
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Authors: Giuseppe Lo Russo; Sara Pusceddu; Natalie Prinzi; Martina Imbimbo; Claudia Proto; Diego Signorelli; Milena Vitali; Monica Ganzinelli; Marco Maccauro; Roberto Buzzoni; Ettore Seregni; Filippo de Braud; Marina Chiara Garassino Journal: Tumour Biol Date: 2016-07-27
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