Radiopharmaceutical development of radiolabelled peptides

Eur J Nucl Med Mol Imaging. 2012 Feb:39 Suppl 1:S11-30. doi: 10.1007/s00259-011-2001-z.

Abstract

Receptor targeting with radiolabelled peptides has become very important in nuclear medicine and oncology in the past few years. The overexpression of many peptide receptors in numerous cancers, compared to their relatively low density in physiological organs, represents the molecular basis for in vivo imaging and targeted radionuclide therapy with radiolabelled peptide-based probes. The prototypes are analogs of somatostatin which are routinely used in the clinic. More recent developments include somatostatin analogs with a broader receptor subtype profile or with antagonistic properties. Many other peptide families such as bombesin, cholecystokinin/gastrin, glucagon-like peptide-1 (GLP-1)/exendin, arginine-glycine-aspartic acid (RGD) etc. have been explored during the last few years and quite a number of potential radiolabelled probes have been derived from them. On the other hand, a variety of strategies and optimized protocols for efficient labelling of peptides with clinically relevant radionuclides such as (99m)Tc, M(3+) radiometals ((111)In, (86/90)Y, (177)Lu, (67/68)Ga), (64/67)Cu, (18)F or radioisotopes of iodine have been developed. The labelling approaches include direct labelling, the use of bifunctional chelators or prosthetic groups. The choice of the labelling approach is driven by the nature and the chemical properties of the radionuclide. Additionally, chemical strategies, including modification of the amino acid sequence and introduction of linkers/spacers with different characteristics, have been explored for the improvement of the overall performance of the radiopeptides, e.g. metabolic stability and pharmacokinetics. Herein, we discuss the development of peptides as radiopharmaceuticals starting from the choice of the labelling method and the conditions to the design and optimization of the peptide probe, as well as some recent developments, focusing on a selected list of peptide families, including somatostatin, bombesin, cholecystokinin/gastrin, GLP-1/exendin and RGD.

Publication types

  • Review

MeSH terms

  • Drug Design*
  • Female
  • Humans
  • Isotope Labeling / methods*
  • Male
  • Neoplasms / diagnostic imaging
  • Neoplasms / radiotherapy
  • Peptides / chemistry
  • Peptides / isolation & purification*
  • Peptides / therapeutic use
  • Radionuclide Imaging
  • Radiopharmaceuticals / chemistry
  • Radiopharmaceuticals / isolation & purification*
  • Radiopharmaceuticals / therapeutic use
  • Receptors, Peptide / metabolism

Substances

  • Peptides
  • Radiopharmaceuticals
  • Receptors, Peptide