The role of radioactive somatostatin and its analogues in the control of tumor growth

Recent Results Cancer Res. 2000:153:1-13. doi: 10.1007/978-3-642-59587-5_1.

Abstract

Peptide receptor scintigraphy with the radioactive somatostatin analogue [111In-DTPA-D-Phe1]octreotide is a sensitive and specific technique to show in vivo the presence and abundance of somatostatin receptors on various tumors. With this technique primary tumors and metastases of neuroendocrine cancers as well as of many other cancer types can be localized. This technique is currently used to assess the possibility of peptide receptor radionuclide therapy with repeated administration of high doses of [111In-DTPA-D-Phe1]octreotide. 111In emits Auger and conversion electrons, having a tissue penetration of 0.02-10 microns and 200-500 microns, respectively. Thirty end-stage patients with mostly neuroendocrine progressing tumors were treated with [111In-DTPA-D-Phe1]octreotide, up to a maximal cumulative patient dose of about 74 GBq, in a phase-I trial. There were no major clinical side effects after up to 2 years of treatment, except that in a few patients a transient decline in platelet counts and lymphocyte subsets occurred. Promising beneficial effects on clinical symptoms, hormone production, and tumor proliferation were found. Of the 21 patients who received a cumulative dose of more than 20 GBq, eight showed stabilization of disease and six others a reduction in tumor size. There is a tendency towards better results in patients whose tumors have a higher accumulation of the radioligand. Peptide receptor radionuclide therapy is also feasible with 111In as the radionuclide. Theoretically, depending on the homogeneity of distribution of tumor cells expressing peptide receptors and the size of the tumor, beta-emitting radionuclides, e.g., 90Y, labeled to DOTA-chelated peptides may be more effective than 111In for peptide receptor radionuclide therapy. The first peptide receptor radionuclide therapy trials with [90Y-DOTA-Tyr3]octreotide started recently.

Publication types

  • Clinical Trial
  • Clinical Trial, Phase I

MeSH terms

  • Cell Division / radiation effects
  • Dose-Response Relationship, Radiation
  • Female
  • Humans
  • Indium Radioisotopes / adverse effects
  • Indium Radioisotopes / therapeutic use*
  • Neuroendocrine Tumors / metabolism
  • Neuroendocrine Tumors / pathology
  • Neuroendocrine Tumors / radiotherapy*
  • Octreotide / adverse effects
  • Octreotide / analogs & derivatives*
  • Octreotide / pharmacokinetics
  • Octreotide / therapeutic use
  • Pentetic Acid* / analogs & derivatives*
  • Radiopharmaceuticals / adverse effects
  • Radiopharmaceuticals / pharmacokinetics
  • Radiopharmaceuticals / therapeutic use*
  • Radiotherapy Dosage

Substances

  • Indium Radioisotopes
  • Radiopharmaceuticals
  • SDZ 215-811
  • Pentetic Acid
  • Octreotide