Antitumor and antiangiogenic effects of somatostatin receptor-targeted in situ radiation with (111)In-DTPA-JIC 2DL

J Surg Res. 2001 May 15;97(2):131-7. doi: 10.1006/jsre.2001.6149.

Abstract

Introduction: Expression of somatostatin receptor subtype 2 (sst 2) in angiogenic tumor vessels appears to be homogeneous, while tumor cell expression of this receptor is often heterogeneous. We have developed a novel in vitro three-dimensional tumor angiogenesis model to study the antitumor and the antiangiogenic effects of radiolabeled somatostatin analogs. We hypothesized that targeted in situ radiation with an Auger electron-emitting radiolabeled somatostatin analog would produce receptor-specific cytotoxicity in sst 2-expressing cells.

Materials and methods: IMR-32 human neuroblastoma (sst 2-positive) and MDA MB-231 human breast cancer (sst 2-negative) xenografts were created in nude mice from monolayer cell cultures. Fragments of these tumors were embedded in three-dimensional fibrin gels supplemented with endothelial growth media and incubated for a period of 14 days. Tumor fragments were treated with 50 microCi/ml of (111)In-JIC 2DL, a sst 2-preferring somatostatin analog, or medium on Day 1. Initial angiogenic activity was determined at 48 h and the mean angiogenic score and tumoricidal responses were assessed on Day 14.

Results and conclusion: Tumoricidal effects of (111)In-JIC 2DL were seen only in sst 2-positive IMR-32 tumors. However, the angiogenic response was inhibited in both IMR-32 and MDA MB-231 tumors independent of the tumor cells' sst 2 status. Somatostatin receptor-mediated in situ radiation therapy has profound cytotoxic effects on angiogenic blood vessels and sst 2-expressing tumor cells.

MeSH terms

  • Adenocarcinoma
  • Amino Acid Sequence
  • Animals
  • Breast Neoplasms
  • Contrast Media / pharmacology*
  • Female
  • Humans
  • In Vitro Techniques
  • Indium Radioisotopes / pharmacology*
  • Mice
  • Mice, Nude
  • Molecular Sequence Data
  • Neoplasm Transplantation
  • Neovascularization, Pathologic / radiotherapy*
  • Neuroblastoma
  • Octreotide / chemistry
  • Octreotide / pharmacology
  • Pentetic Acid / analogs & derivatives
  • Pentetic Acid / pharmacology*
  • Receptors, Somatostatin / metabolism*
  • Tumor Cells, Cultured

Substances

  • Contrast Media
  • Indium Radioisotopes
  • Receptors, Somatostatin
  • Pentetic Acid
  • somatostatin receptor 2
  • Octreotide