Lutetium-177-labeled gastrin releasing peptide receptor binding analogs: a novel approach to radionuclide therapy

Q J Nucl Med Mol Imaging. 2006 Dec;50(4):310-21.

Abstract

Optimization of therapy for individual patients remains a goal of clinical practice. Radionuclide imaging can identify those patients who may benefit from subsequent targeted therapy by providing regional information on the distribution of the target. An ideal situation may be when the imaging and the therapeutic compounds are the same agent. Two antibodies ([ [90Y]ibritumomab, [131I]tositumomab) are now approved for the systemic radiotherapy of non-Hodgkin's lymphoma. The main hurdle is to deliver higher absorbed doses to the more refractory solid tumors paying particular regard to the bone marrow toxicity. The low dose is thought to be a result of the large size of antibodies slowing delivery to the target. Peptides having high affinity to receptors expressed on cancer cells are a promising alternative. They are usually rapidly excreted from the body through renal and/or hepatobiliary excretion thus creating a prolonged accumulation of the radioactivity in the kidneys, which represents a recognized issue for systemic radiotherapy. The first radiopeptide developed was a somatostatin analogue, which led to a major breakthrough in the field. Beside the kidney issue, somatostatin use remains limited to few cancers that express receptors in sufficiently large quantities, mainly neuroendocrine tumors. The gastrin releasing peptide (GRP) receptor is an attractive target for development of new radiopeptides with diagnostic and therapeutic potential. This is based upon the functional expression of GRP receptors in several of the more prevalent cancers including prostate, breast, and small cell lung cancer. This review covers the efforts currently underway to develop new and clinically promising GRP-receptor specific molecules labeled with imageable and therapeutic radionuclides.

Publication types

  • Review

MeSH terms

  • Antibodies, Monoclonal / pharmacokinetics
  • Antibodies, Monoclonal / therapeutic use
  • Drug Delivery Systems / methods
  • Gastrin-Releasing Peptide / analogs & derivatives*
  • Gastrin-Releasing Peptide / therapeutic use*
  • Humans
  • Lutetium / pharmacokinetics*
  • Lutetium / therapeutic use*
  • Neoplasms / diagnostic imaging
  • Neoplasms / metabolism*
  • Neoplasms / radiotherapy*
  • Radioisotopes / pharmacokinetics
  • Radioisotopes / therapeutic use
  • Radionuclide Imaging
  • Radiopharmaceuticals / pharmacokinetics
  • Radiopharmaceuticals / therapeutic use
  • Receptors, Bombesin / metabolism*

Substances

  • Antibodies, Monoclonal
  • Radioisotopes
  • Radiopharmaceuticals
  • Receptors, Bombesin
  • Lutetium
  • Gastrin-Releasing Peptide