Increased Cell Death After Therapy with an Arg-Gly-Asp-Linked Somatostatin Analog

Journal of Nuclear Medicine

Bert F. Bernard¹  Eric P. Krenning¹  Astrid Capello¹  Wout A.P. Breeman¹  Martin P. van Hagen¹  Marion de Jong¹ 

关键词: apoptosis;    caspase-3;    octreotate;    radionuclide therapy;    Arg-Gly-Asp;   

DOI  :  

学科分类：医学（综合）

来源: Society of Nuclear Medicine

【 摘 要 】

Receptor-targeted scintigraphy and radionuclide therapy with radiolabeled somatostatin analogs are successfully applied for somatostatin receptor-positive tumors. The synergistic effects of an apoptosis-inducing factor, for example, the Arg-Gly-Asp (RGD) motif, can increase the radiotherapeutic efficacy of these peptides. Hence, the tumoricidal effects of the hybrid peptide RGD-diethylaminetriaminepentaacetic acid (DTPA)-Tyr3-octreotate (cyclic[c](Arg-Gly-Asp-d-Tyr-Asp)-Lys(DTPA)-d-Phe-c(Cys-Tyr-d-Trp-Lys-Thr-Cys)-Thr), hereafter referred to as RGD-DTPA-octreotate, were evaluated in comparison with those of RGD (c(Arg-Gly-Asp-d-Tyr-Asp)) and Tyr3-octreotate (d-Phe-c(Cys-Tyr-d-Trp-Lys-Thr-Cys)-Thr). Methods: The therapeutic effects of RGD-111In-DTPA-octreotate, 111In-DTPA-RGD, and 111In-DTPA-Tyr3-octreotate were investigated with various cell lines by use of a colony-forming assay, and caspase-3 activity was also determined. Results: Tumoricidal effects were found with 111In-DTPA-RGD, 111In-DTPA-Tyr3-octreotate, and RGD-111In-DTPA-octreotate, in order from least effective to most effective. Also, the largest increase in caspase-3 levels was found with RGD-111In-DTPA-octreotate. Conclusion: RGD-111In-DTPA-octreotate has more pronounced tumoricidal effects than 111In-DTPA-RGD and 111In-DTPA-Tyr3-octreotate, because of increased apoptosis, as indicated by increased caspase-3 activity.

【 授权许可】

Unknown