Synthesis and Evaluation of Technetium-99m-Labeled Bioreductive Pharmacophores Conjugated with Amino Acids and Peptides for Tumor Imaging
IR@IICB: CSIR-Indian Institute of Chemical Biology, Kolkata
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| Title |
Synthesis and Evaluation of Technetium-99m-Labeled
Bioreductive Pharmacophores Conjugated with Amino Acids and Peptides for Tumor Imaging
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| Creator |
Baishya, Rinku
Nayak, Dipak K. Karmakar, Sanmoy Chattopadhyay, Sankha Sachdeva, Satbir S Sarkar, Bharat R Ganguly, Shantanu Debnath, Mita C |
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| Subject |
Infectious Diseases and Immunology
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| Description |
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�2M). 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 avb3 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 avb3-positive B16F10 mouse melanoma cell line. The
ligands caused only 8–13% of hemolysis toward rat
erythrocytes at concentrations as high as 100 lM.
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.
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| Date |
2015
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| Type |
Article
PeerReviewed |
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| Format |
application/pdf
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| Identifier |
http://www.eprints.iicb.res.in/2208/1/CHEMICAL_BIOLOGY_%26_DRUG_DESIGN__V._85__(_4)s_504%2D517;2015[36].pdf
Baishya, Rinku and Nayak, Dipak K. and Karmakar, Sanmoy and Chattopadhyay, Sankha and Sachdeva, Satbir S and Sarkar, Bharat R and Ganguly, Shantanu and Debnath, Mita C (2015) Synthesis and Evaluation of Technetium-99m-Labeled Bioreductive Pharmacophores Conjugated with Amino Acids and Peptides for Tumor Imaging. Chemical Biology & Drug Design, 85 (4). pp. 504-517. |
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| Relation |
http://www.eprints.iicb.res.in/2208/
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