Radiolabelled peptides for tumour therapy: current status and future directions. Plenary lecture at the EANM 2002

Eur J Nucl Med Mol Imaging. 2003 Mar;30(3):463-9. doi: 10.1007/s00259-002-1107-8. Epub 2003 Feb 5.

Abstract

On their plasma membranes, cells express receptor proteins with high affinity for regulatory peptides, such as somatostatin. Changes in the density of these receptors during disease, e.g. overexpression in many tumours, provide the basis for new imaging methods. The first peptide analogues successfully applied for visualisation of receptor-positive tumours were radiolabelled somatostatin analogues. The next step was to label these analogues with therapeutic radionuclides for peptide receptor radionuclide therapy (PRRT). Results from preclinical and clinical multicentre studies have already shown an effective therapeutic response when using radiolabelled somatostatin analogues to treat receptor-positive tumours. Infusion of positively charged amino acids reduces kidney uptake, enlarging the therapeutic window. For PRRT of CCK-B receptor-positive tumours, such as medullary thyroid carcinoma, radiolabelled minigastrin analogues are currently being successfully applied. The combination of different therapy modalities holds interest as a means of improving the clinical therapeutic effects of radiolabelled peptides. The combination of different radionuclides, such as (177)Lu- and (90)Y-labelled somatostatin analogues, to reach a wider tumour region of high curability, has been described. A variety of other peptide-based radioligands, such as bombesin and NPY(Y(1)) analogues, receptors for which are expressed on common cancers such as prostate and breast cancer, are currently under development and in different phases of (pre)clinical investigation. Multi-receptor tumour targeting using the combination of bombesin and NPY(Y(1)) analogues is promising for scintigraphy and PRRT of breast carcinomas and their lymph node metastases.

Publication types

  • Review

MeSH terms

  • Humans
  • Neoplasms / radiotherapy*
  • Peptides / therapeutic use*
  • Radioisotopes / therapeutic use*
  • Radiopharmaceuticals / therapeutic use
  • Radiotherapy / methods*
  • Radiotherapy / trends*

Substances

  • Peptides
  • Radioisotopes
  • Radiopharmaceuticals