Synthesis, radiolabelling and biological characteristics of a bombesin peptide analog as a tumor imaging agent

Anticancer Res. 2003 May-Jun;23(3B):2745-50.

Abstract

Background: Several human cancers, including small cell lung, prostate, breast, gastric, colon and pancreatic cancers, express receptors for bombesin-like peptides. Bombesin (BN) peptides that bind specifically to these receptors are useful for detection of bombesin receptor-expressing cancers in vivo. A new 99mTc-labelled-BN peptide for targeting bombesin receptor-expressing cancers was prepared and characterized.

Materials and methods: MAG3-coupled BN peptide (MAG3-BN) was prepared by solid-phase synthesis and radiolabelled with 99mTc by an exchange method. In vitro cell binding assays were conducted on human breast cancer cell lines, MDA-MB-231 and MCF-7. In vivo biodistribution studies were performed in normal and nude mice bearing bombesin receptor-positive tumors.

Results: Radiolabelling of MAG3-BN with 99mTc produces a single radioactive species (> 95%). In vitro cell-binding indicated the affinity and specificity of 99mTc-MAG3-BN towards bombesin receptors. In vivo biodistribution in mice demonstrated that 99mTc-MAG3-BN cleared rapidly from the blood and most non-targeted tissues and was excreted mainly via the kidneys. Uptake in bombesin receptor-positive tissues and in the tumor was low to moderate.

Conclusion: 99mTc-MAG3-BN displays good radiolabelling together with certain favorable biological characteristics and might be a useful peptide radiopharmaceutical in the detection of bombesin receptor-expressing cancers in vivo.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • 3T3 Cells
  • Amino Acid Sequence
  • Animals
  • Bombesin / analogs & derivatives*
  • Bombesin / chemical synthesis
  • Bombesin / pharmacokinetics
  • Breast Neoplasms / diagnostic imaging
  • Breast Neoplasms / metabolism
  • Cysteine / chemistry
  • Female
  • Humans
  • Isotope Labeling
  • Male
  • Mice
  • Molecular Sequence Data
  • Radionuclide Imaging
  • Radiopharmaceuticals / chemical synthesis*
  • Radiopharmaceuticals / pharmacokinetics*
  • Receptors, Bombesin / antagonists & inhibitors
  • Receptors, Bombesin / metabolism
  • Technetium Compounds / chemical synthesis*
  • Technetium Compounds / pharmacokinetics*
  • Technetium Tc 99m Mertiatide / analogs & derivatives
  • Technetium Tc 99m Mertiatide / chemical synthesis*
  • Technetium Tc 99m Mertiatide / pharmacokinetics*
  • Tissue Distribution
  • Tumor Cells, Cultured

Substances

  • 99mTc-MAG3-Pro3-BN
  • Radiopharmaceuticals
  • Receptors, Bombesin
  • Technetium Compounds
  • Technetium Tc 99m Mertiatide
  • Cysteine
  • Bombesin