We found a match
Your institution may have access to this item. Find your institution then sign in to continue.
- Title
Preparation and preliminary evaluation of a tris-metronidazole-<sup>99m</sup>Tc(CO)<sub>3</sub> complex for targeting tumor hypoxia.
- Authors
Mallia, Madhava B.; Mathur, Anupam; Sharma, Rohit; Kumar, Chandan; Sarma, H. D.; Banerjee, Sharmila; Dash, Ashutosh
- Abstract
Conventional 99mTc-radiopharmaceuticals for the detection of tumor hypoxia generally possess a single nitroimidazole moiety. Herein, we report the synthesis and evaluation of a 99mTc-complex with three-nitroimidazole moieties in an attempt to improve hypoxic cell detection. Isocyanide derivative of metronidazole (MetroNC) was synthesized and subsequently radiolabeled with [99mTc(CO)3(H2O)3]+ precursor complex, wherein the three labile water molecules were replaced with MetroNC ligand to form a pseudo-octahedral [99mTc(CO)3(MetroNC)3]+ complex. Analysis of corresponding Re(CO)3-analog prepared in macroscopic scale confirmed the formation of expected complex. Cyclic voltammetric studies of [Re(CO)3(MetroNC)3]+ complex showed no significant change in single-electron reduction potential (SERP) of MetroNC ligand (− 0.96 V) upon forming the [Re(CO)3(MetroNC)3]+ complex (− 0.90 V). In vitro studies in Chinese hamster ovary (CHO) cells showed three-fold preferential accumulation of [99mTc(CO)3(MetroNC)3]+ complex in hypoxic cells over normoxic cells. Biodistribution studies of [99mTc(CO)3(MetroNC)3]+ complex in Swiss mice bearing fibrosarcoma tumor showed tumor uptake and steady retention till 60 min post injection. Present study constitutes a novel design approach towards development of a 99mTc-radiopharmaceutical for hypoxia imaging application, which could be extended to other potential nitroimidazole ligands.
- Subjects
METRONIDAZOLE; ANTIPARASITIC agents; NITROIMIDAZOLES; RADIOPHARMACEUTICALS; MEDICAL radiology
- Publication
Journal of Radioanalytical & Nuclear Chemistry, 2018, Vol 317, Issue 3, p1203
- ISSN
0236-5731
- Publication type
Article
- DOI
10.1007/s10967-018-6012-0