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Coligand effects on the solution stability, biodistribution and metabolism of the (99m)Tc-labeled cyclic RGDfK tetramer.

Abstract
In this study, we present the evaluation of two new ternary ligand (99m)Tc complexes [(99m)Tc(HYNIC tetramer)(tricine)(L)] [L=isonicotinic acid (ISONIC) and 2,5-pyridinedicarboxylic acid (PDA)] as potential radiotracers for tumor imaging. Athymic nude mice bearing MDA-MB-435 human breast cancer xenografts were used to evaluate their biodistribution and metabolic properties. Solution stability data showed that [(99m)Tc(HYNIC tetramer)(tricine)(L)] (L=ISONIC and PDA) had significant decomposition (14% and 35%, respectively) at 6 h in the absence of excess ISONIC or PDA coligand. Biodistribution data clearly showed that [(99m)Tc(HYNIC tetramer)(tricine)(PDA)] had a much lower uptake in most organs of interest than [(99m)Tc(HYNIC tetramer)(tricine)(ISONIC)] during the 2-h study period. Results from metabolism studies revealed that approximately 50% of [(99m)Tc(HYNIC tetramer)(tricine)(ISONIC)] remained intact in fecal samples at 120 min postinjection, whereas only 10% of [(99m)Tc(HYNIC tetramer)(tricine)(PDA)] remained intact in fecal samples. The extent of metabolism correlated well with radiotracer solution stability. The results from this and our previous studies clearly demonstrated that coligands [trisodium triphenylphosphine-3,3',3''-trisulfonate (TPPTS), ISONIC and PDA] have a significant impact on the tumor uptake, excretion kinetics and metabolism of the (99m)Tc-labeled cyclic RGDfK tetramer. Among the three radiotracers evaluated in this tumor-bearing animal model, [(99m)Tc(HYNIC tetramer)(tricine)(TPPTS)] remained the best with respect to blood clearance, tumor uptake and target/background ratios.
AuthorsShuang Liu, Young-Seung Kim, Wen-Yuan Hsieh, Subramanya Gupta Sreerama
JournalNuclear medicine and biology (Nucl Med Biol) Vol. 35 Issue 1 Pg. 111-21 (Jan 2008) ISSN: 0969-8051 [Print] United States
PMID18158950 (Publication Type: Journal Article, Research Support, N.I.H., Extramural, Research Support, Non-U.S. Gov't)
Chemical References
  • Ligands
  • Organotechnetium Compounds
  • Peptides, Cyclic
  • Radiopharmaceuticals
  • cyclic arginine-glycine-aspartic acid peptide
Topics
  • Animals
  • Chromatography, High Pressure Liquid
  • Female
  • Humans
  • Ligands
  • Mice
  • Neoplasm Transplantation
  • Neoplasms, Experimental (diagnostic imaging, metabolism)
  • Organotechnetium Compounds
  • Peptides, Cyclic (metabolism)
  • Radionuclide Imaging
  • Radiopharmaceuticals (metabolism)
  • Tissue Distribution
  • Transplantation, Heterologous

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