Assessment of therapeutic tumor response using 99mtc-ethylenedicysteine-glucosamine

Cancer Biother Radiopharm. 2004 Aug;19(4):443-56. doi: 10.1089/cbr.2004.19.443.

Abstract

Purpose: The aim of this study was to evaluate 99mTc-ethylenedicysteine-glucosamine (EC-DG) for the assessment of tumor growth.

Method: To evaluate whether 99mTc-EC-DG is involved in cell nuclei activity, in vitro thymidine incorporation, and cell-cycle assays of EC-DG were conducted using lung and breast cancer cells. Biodistribution of 99mTc-EC-DG in lung tumor-bearing mice (0.5-4 hours, 1 Ci/mouse, i. v.) was used to estimate the radiation-absorbed dose. Autoradiograms of 99mTc-EC-DG and 18F-FDG were compared in nude mice bearing uterine sarcoma. Rabbits inoculated with VX-2 cells were imaged with 99mTc-EC-DG and 99mTc-EC. For therapeutic assessment studies, scintigraphic imaging studies with 99mTc-EC-DG in mammary tumor-bearing rats were conducted at various days after treatment with paclitaxel and cisplatin. The imaging findings were correlated immunohistochemical assays (mRNA expression, apoptosis, and cell-cycle changes in tumor), and flow cytometry analysis was performed.

Results: In vitro cellular uptake assays indicated that cell nuclei activity could be assessed by 99mTc-EC-DG. Scintigraphy and autoradiograms in animal models demonstrated that the tumor could be clearly visualized by 99mTc-EC-DG. The efficacy of paclitaxel and cisplatin treatment in rodent models could be assessed using tumor/muscle ratios. Immunohistochemical staining indicated a reduced expression of bFGF and an increased apoptosis and cell-cycle changes after paclitaxel and cisplatin treatment.

Conclusion: 99mTc-EC-DG is involved in cell nuclei activity and could assess the therapeutic tumor response.

Publication types

  • Research Support, Non-U.S. Gov't
  • Research Support, U.S. Gov't, P.H.S.

MeSH terms

  • Animals
  • Apoptosis / drug effects
  • Autoradiography
  • Cell Cycle / drug effects
  • Cell Division / drug effects
  • Cysteine / analogs & derivatives*
  • Cysteine / metabolism*
  • Female
  • Glucosamine / metabolism*
  • Glucose / metabolism
  • Mice
  • Neoplasms, Experimental / drug therapy*
  • Neoplasms, Experimental / metabolism
  • Neoplasms, Experimental / pathology
  • Organotechnetium Compounds*
  • Rabbits
  • Radiometry
  • Radiopharmaceuticals*
  • Thymidine / metabolism

Substances

  • Organotechnetium Compounds
  • Radiopharmaceuticals
  • ethylene dicysteine
  • Glucose
  • Cysteine
  • Glucosamine
  • Thymidine