Radiation Induces Up-Regulation of Somatostatin Receptors 1, 2, and 5 in Small Cell Lung Cancer In Vitro Also at Low Absorbed Doses

Abstract

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. 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. 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. 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.