Radiolabeled RGD-DTPA-Tyr3-octreotate for receptor-targeted radionuclide therapy

Cancer Biother Radiopharm. 2004 Apr;19(2):173-80. doi: 10.1089/108497804323071940.

Abstract

The aim of this study was to develop and investigate a radiopeptide for the treatment of cancers which overexpress cell surface somatostatin receptors. The new radiopharmaceutical is composed of a somatostatin receptor-targeting peptide, a chelator (DTPA) to enable radiolabeling, and an apoptosis-inducing RGD (arginine-glycine-aspartate) peptide moiety. The receptor-targeting peptide portion of the molecule, Tyr3-octreotate, is specific for the somatostatin subtype-2 cell surface receptor (sst2), which is overexpressed on many tumor cells. Because of the rapid endocytosis of the somatostatin receptor, the entire molecule can thus be internalized, allowing the RGD portion to activate intracellular caspases, which in turn promotes apoptosis. In this paper, we present the synthesis and the in vitro and in vivo tumor binding and internalization characteristics of this hybrid peptide. In vitro internalization into sst2-positive tumor cells of the radiolabeled hybrid peptide appeared to be a rapid process and could be blocked by an excess of unlabeled octreotide, indicating an sst2-specific process. Tumor uptake in vivo in rats of radiolabeled RGD-DTPA-Tyr3-octreotate was in agreein vitro data and similar to that of radiolabeled DOTA-Tyr3-octreotate. The combined molecule is expected to significantly enhance the therapeutic efficacy of the somatostatin-based agent.

MeSH terms

  • Animals
  • Cell Line, Tumor
  • Indium Radioisotopes / metabolism
  • Indium Radioisotopes / pharmacokinetics
  • Indium Radioisotopes / therapeutic use*
  • Neoplasms / radiotherapy*
  • Oligopeptides / chemistry
  • Oligopeptides / metabolism
  • Oligopeptides / pharmacokinetics
  • Oligopeptides / therapeutic use*
  • Pentetic Acid / chemistry*
  • Pentetic Acid / pharmacokinetics
  • Peptides, Cyclic / chemistry
  • Peptides, Cyclic / metabolism*
  • Peptides, Cyclic / pharmacokinetics
  • Rats
  • Receptors, Somatostatin / metabolism*
  • Sensitivity and Specificity
  • Tissue Distribution

Substances

  • Indium Radioisotopes
  • Oligopeptides
  • Peptides, Cyclic
  • Receptors, Somatostatin
  • octreotate, Tyr(3)-
  • arginyl-glycyl-aspartic acid
  • Pentetic Acid
  • somatostatin receptor 2