Synthesis and evaluation of technetium-99m-labeled bioreductive pharmacophores conjugated with amino acids and peptides for tumor imaging

Rinku Baishya, Dipak K. Nayak, Sanmoy Karmakar, Sankha Chattopadhyay, Satbir S. Sachdeva, Bharat R. Sarkar, Shantanu Ganguly, Mita C. Debnath

Research output: Contribution to journalArticlepeer-review

10 Scopus citations


Development of molecular imaging agents to target tumor has become a major trend in nuclear medicine. With the aim to develop new potential 99mTc-radiopharmaceuticals for targeting tumor, we have synthesized 5-nitroimidazolyl amino acids and RGD-coupled 2-nitroimidazoles. Technetium-99m radiolabeling with high radiochemical purity (>90%) was achieved for all the compounds. The radiolabeled complexes exhibited substantial in vitro stability in saline, serum, and histidine solution (10-2 m). Cell binding studies in EAC and B16F10 cell lines also revealed rapid and comparatively high cellular internalization. Among all the compounds studied, the binding of 99mTc(CO)3-5 to B16F10 cells was moderately inhibited by the competitive peptide c[RGDfV], suggesting specificity of the radioligand toward αvβ3 receptor. However, no significant displacement of bound radioligand was observed when the binding of the 99mTc-labeled complexes to above cells was challenged with excess competitive peptide. Fluorescent microscopy study provided direct evidence of intracellular localization of 5(6)-carboxyfluorescein-labeled 2-nitroimidazolyl-RGD-peptide in αvβ3-positive B16F10 mouse melanoma cell line. The ligands caused only 8-13% of hemolysis toward rat erythrocytes at concentrations as high as 100 μm. Imaging and biodistribution studies were performed in Swiss albino mice bearing induced tumor. 99mTc-1 and 99mTc(CO)3-5 demonstrated a very favorable in vivo profile. Selective uptake and retention in tumor with encouraging tumor/muscle and tumor/blood ratio and significant cellular uptake of fluorescence-labeled-2-nitroimidazolyl RGD indicate the great potentiality of the pharmacophore for further evaluation as potential molecular imaging agent in cancer diagnosis.

Original languageEnglish
Pages (from-to)504-517
Number of pages14
JournalChemical Biology and Drug Design
Issue number4
StatePublished - 1 Jan 2015
Externally publishedYes


  • amino acids and peptides
  • bioreductive pharmacophore
  • technetium-99m labeling
  • tumor imaging

ASJC Scopus subject areas

  • Biochemistry
  • Molecular Medicine
  • Pharmacology
  • Drug Discovery
  • Organic Chemistry


Dive into the research topics of 'Synthesis and evaluation of technetium-99m-labeled bioreductive pharmacophores conjugated with amino acids and peptides for tumor imaging'. Together they form a unique fingerprint.

Cite this