Somatostatin-receptor-targeted α-emitting 213Bi is therapeutically more effective than β-emitting 177Lu in human pancreatic adenocarcinoma cells

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 Bi-213 to that of low-LET emitting Lu-177 by determining relative biological effectiveness (RBE) using the external gamma-beam of Cs-137 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 Bi-213 and Lu-177 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 10 x kit. Results: Using equimolar DOTATOC treatment with concurrent irradiation with a Cs-137 source as reference radiation, the calculated RBE of [Bi-213]DOTATOC was 3.4, as compared to 1.0 for [Lu-177]DOTATOC. As measured in terms of absorbance units, [Bi-213]DOTATOC caused a 2.3-fold-greater release of apoptosis-specific mononucleosomes and oligonucleosomes than [Lu-177]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, [Bi-213]DOTATOC is therapeutically more effective in decreasing survival than is [Lu-177]DOTATOC in human pancreatic adenocarcinoma cells due to its comparatively higher RBE. (c) 2007 Elsevier Inc. All rights reserved.