Preparation and evaluation of a ⁹⁹mTcN-PNP complex of sanazole analogue for detecting tumor hypoxia.

A sanazole derivative, having a favorable single electron reduction potential (SERP) value compared to that of misonidazole, was synthesized and radiolabeled with [(99m)TcN(PNP)] precursor to evaluate its potential as a hypoxia imaging agent. The complex, which was lipophilic, could be prepared in good yields and challenging studies with cysteine showed stability of the complex against trans-chelation. However, despite being lipophilic as well as possessing favorable SERP value, biodistribution studies of this complex in fibrosarcoma tumor bearing Swiss mice showed low uptake in tumor. This observation is possibly attributed to fast clearance of the complex from blood, whereby the complex spends insufficient time in tumor to get reduced and trapped. Though uptake in tumor was low, slow clearance of activity from tumor suggests reduction and trapping of the complex in hypoxic cells. The present (99m)Tc-complex demonstrated acceptable values of tumor to blood (TBR) and tumor to muscle (TMR) ratios. However, low uptake in tumor which may not be indicative of the actual hypoxic status of the tumor, limit the utility of the complex to detect tumor hypoxia.
AuthorsAnupam Mathur, Madhava B Mallia, Sharmila Banerjee, H D Sarma, M R A Pillai
JournalBioorganic & medicinal chemistry letters (Bioorg Med Chem Lett) Vol. 23 Issue 5 Pg. 1394-7 (Mar 1 2013) ISSN: 1464-3405 [Electronic] England
PMID23375795 (Publication Type: Journal Article)
CopyrightCopyright © 2013 Elsevier Ltd. All rights reserved.
Chemical References
  • Organotechnetium Compounds
  • Radiopharmaceuticals
  • Triazoles
  • AK 2123
  • Animals
  • Cell Hypoxia (physiology)
  • Fibrosarcoma (metabolism, radionuclide imaging)
  • Mice
  • Organotechnetium Compounds (chemical synthesis, chemistry, pharmacokinetics)
  • Radiopharmaceuticals (chemical synthesis, chemistry, pharmacokinetics)
  • Triazoles (chemical synthesis, chemistry, pharmacokinetics)

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