HOMEPRODUCTSCOMPANYCONTACTFAQResearchDictionaryPharmaSign Up FREE or Login

A study on nitroimidazole-99mTc(CO)3 complexes as hypoxia marker: some observations towards possible improvement in in vivo efficacy.

AbstractINTRODUCTION:
Hypoxia plays a negative role in the clinical management of cancer. Detection of hypoxic status of a cancer is important for selecting patients for hypoxia directed therapy. Though [(18)F]fluoromisonidazole ([(18)F]FMISO), a PET radiopharmaceutical, is presently being used in the clinic for the detection of hypoxia, considering the logistical advantages of (99m)Tc and wider availability of SPECT scanners, a radiopharmaceutical based on this isotope may find wider applicability.
METHODS:
Nine nitroimidazole (2-, 4- and 5-nitroimidazole) ligands were synthesized and radiolabeled using [(99m)Tc(CO)3(H2O)3](+) precursor to obtain a group of complexes possessing different single electron reduction potential (SERP), overall charge and lipophilicity, the three attributes which decide the efficacy of the complex to detect hypoxic cells in vivo. The nitroimidazole-(99m)Tc(CO)3 complexes as well as [(18)F]FMISO were evaluated in fibrosarcoma tumor bearing mice.
RESULTS:
The (99m)Tc(CO)3 complexes of nitroimidazole iminodiacetic acid (IDA) showed better tumor uptake and retention than nitroimidazole diethylenetriamine (DETA) and nitroimidazole aminoethylglycine (AEG) complexes. Tumor uptake observed with [(18)F]FMISO was higher than any of the nitroimidazole-IDA- (99m)Tc(CO)3 complexes. However, [(18)F]FMISO clearance from tumor was found to be faster compared to 2-nitroimidazole-IDA-(99m)Tc(CO)3 complex. Observed tumor uptake and retention of the radiotracers evaluated could be correlated to its blood clearance pattern and SERP.
CONCLUSIONS:
Results of the present study indicated that uptake of the radiotracer in tumor is closely associated with its rate of clearance from blood. The study also indicated that along with SERP, clearance of radiotracer from blood (net effect of charge and lipophilicity) is a critical factor which decides the in vivo efficacy of the hypoxia detecting radiopharmaceutical.
AuthorsMadhava B Mallia, Suresh Subramanian, Anupam Mathur, H D Sarma, Sharmila Banerjee
JournalNuclear medicine and biology (Nucl Med Biol) Vol. 41 Issue 7 Pg. 600-10 (Aug 2014) ISSN: 1872-9614 [Electronic] United States
PMID24856280 (Publication Type: Journal Article)
CopyrightCopyright © 2014 Elsevier Inc. All rights reserved.
Chemical References
  • Biomarkers, Tumor
  • Nitroimidazoles
  • Organotechnetium Compounds
  • 4-nitroimidazole
Topics
  • Animals
  • Biological Transport
  • Biomarkers, Tumor (chemistry, metabolism, pharmacokinetics)
  • Cell Hypoxia
  • Fibrosarcoma (pathology)
  • Humans
  • Hydrophobic and Hydrophilic Interactions
  • Mice
  • Nitroimidazoles (chemistry)
  • Organotechnetium Compounds (chemistry, metabolism, pharmacokinetics)
  • Radiochemistry
  • Tissue Distribution

Join CureHunter, for free Research Interface BASIC access!

Take advantage of free CureHunter research engine access to explore the best drug and treatment options for any disease. Find out why thousands of doctors, pharma researchers and patient activists around the world use CureHunter every day.
Realize the full power of the drug-disease research graph!


Choose Username:
Email:
Password:
Verify Password:
Enter Code Shown: