Synthesis and Evaluation of Technetium‐99m‐Labeled Bioreductive Pharmacophores Conjugated with Amino Acids and Peptides for Tumor Imaging. (25th October 2014) - Baishya, Rinku
Abstract : Development of molecular imaging agents to target tumor has become a major trend in nuclear medicine. With the aim to develop new potential 99m Tc‐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 99m Tc(CO)3 ‐5 to B16F10 cells was moderately inhibited by the competitive peptide c[RGDfV], suggesting specificity of the radioligand toward α v β 3 receptor. However, no significant displacement of bound radioligand was observed when the binding of the 99m Tc‐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 α v β 3 ‐positive B16F10 mouse melanoma cell line. The ligands caused only 8–13% of hemolysis toward rat erythrocytes at concentrations as high as 100 μ m . Imaging and biodistribution studies were performed in Swiss albino mice bearing induced tumor. 99m Tc‐1 and 99m Tc(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. Abstract : Technetium‐99m‐labeled 5‐nitroimidazolyl amino acids and RGD‐coupled 2‐nitroimidazoles have been synthesized and reported for molecular imaging agent in cancer diagnosis. Cell binding studies in EAC and B16F10 cell lines also revealed rapid and comparatively high cellular internalization. Scintigraphy and fluorescent microscopy suggest the great potentiality of the pharmacophore as tumor imaging agent.