Synthesis, chemical, radiochemical and radiobiological evaluation of a new 99mTc-labelled bombesin-like peptide

Cancer Biother Radiopharm. 2002 Jun;17(3):317-26. doi: 10.1089/10849780260179288.

Abstract

A new pentadecapeptide bombesin analogue was prepared by Fmoc synthesis, purified by HPLC and identified by electron ionization mass spectrometry. The biological activity of the new peptide was tested on isolated human colonic muscle cells and compared to native bombesin. Labelling of the new biomolecule with Tc-99m yielded a single radioactive species which remained stable at room temperature for eight hours. In a binding assay, the radiolabelled peptide showed high affinity for oat-cell carcinoma (Kd = 9.8 nM) and colorectal adenocarcinoma (Kd = 27.2 nM). Biodistribution studies, performed in normal rodents, indicated uptake by organs that normally express bombesin receptors, such as liver, intestines and kidneys. Scintigraphic studies, performed in nude mice transplanted with small cell lung carcinoma and colon cancer cells, showed significant tumor uptake two hours p.i. The new synthetic pentadecapeptide appears to have promise for several malignancies, including oat-cell lung carcinoma, colorectal cancer and gastroenteropancreatic (GEP) tumors.

Publication types

  • Evaluation Study

MeSH terms

  • Animals
  • Bombesin* / chemical synthesis
  • Bombesin* / pharmacokinetics
  • Carcinoma, Small Cell / diagnostic imaging*
  • Carcinoma, Small Cell / metabolism
  • Colonic Neoplasms / diagnostic imaging*
  • Colonic Neoplasms / metabolism
  • Female
  • Humans
  • Isotope Labeling
  • Lung Neoplasms / diagnostic imaging*
  • Lung Neoplasms / metabolism
  • Mice
  • Mice, Inbred BALB C
  • Mice, Nude
  • Neoplasm Transplantation
  • Peptides* / chemical synthesis
  • Peptides* / pharmacokinetics
  • Radionuclide Imaging
  • Rats
  • Rats, Wistar
  • Receptors, Bombesin / metabolism
  • Sodium Pertechnetate Tc 99m*
  • Tissue Distribution
  • Tumor Cells, Cultured

Substances

  • Peptides
  • Receptors, Bombesin
  • Sodium Pertechnetate Tc 99m
  • Bombesin