(99m)Tc-EC-guanine: synthesis, biodistribution, and tumor imaging in animals

Pharm Res. 2005 Sep;22(9):1471-9. doi: 10.1007/s11095-005-6157-8. Epub 2005 Aug 24.


Purpose: DNA markers are useful in assessing cell proliferation. The purpose of this study was to synthesize (99m)Tc-ethylenedicysteine-guanine (EC-Guan) for evaluation of cell proliferation.

Methods: Tumor cells were incubated with (99m)Tc-EC-Guan for cell cycle analysis. Prostate tumor cells that were overexpressing the HSV thymidine kinase gene, or various tumor cells were incubated with (99m)Tc-EC-Guan at 0.5-2 h. Thymidine incorporation assays were performed in lung cancer cells incubated with EC-Guan at 0.1-1 mg/well. Tissue distribution, autoradiography, and planar scintigraphy of (99m)Tc-EC-Guan and (99m)Tc-EC (control) were determined in tumor-bearing rodents at 0.5-4 h.

Results: Cell culture assays indicated that EC-Guan was incorporated in DNA, and there was no significant uptake difference between HSVTK overexpressed and normal groups. Biodistribution and scintigraphic imaging studies of (99m)Tc-EC-Guan showed increased tumor/tissue count density ratios as a function of time.

Conclusions: Our results indicate that (99m)Tc-EC-Guan may be useful as a tumor proliferation imaging agent.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Autoradiography
  • Cell Cycle
  • Guanine / analogs & derivatives*
  • Guanine / chemical synthesis
  • Guanine / pharmacokinetics
  • Humans
  • Male
  • Organotechnetium Compounds / chemical synthesis*
  • Organotechnetium Compounds / pharmacokinetics*
  • Prostatic Neoplasms / diagnostic imaging
  • Prostatic Neoplasms / enzymology
  • Prostatic Neoplasms / metabolism*
  • Prostatic Neoplasms / pathology
  • Radionuclide Imaging
  • Radiopharmaceuticals / chemical synthesis*
  • Radiopharmaceuticals / pharmacokinetics*
  • Rats
  • Rats, Sprague-Dawley
  • Simplexvirus / enzymology
  • Thymidine Kinase / genetics
  • Thymidine Kinase / metabolism
  • Tissue Distribution
  • Tomography, Emission-Computed, Single-Photon
  • Tumor Cells, Cultured


  • Organotechnetium Compounds
  • Radiopharmaceuticals
  • technetium 99m ethylenedicysteine-9-(4-amino-3-(hydroxymethyl)butyl)guanine conjugate
  • Guanine
  • Thymidine Kinase