Assessment of antiangiogenic effect using 99mTc-EC-endostatin

Cancer Biother Radiopharm. 2002 Apr;17(2):233-45. doi: 10.1089/108497802753773856.


Purpose: Tumor vascular density may provide a prognostic indicator of metastatic potential or survival. The purpose of this study was to develop 99mTc-ethylenedicysteine-endostatin (99mTc-EC-endostatin) for the evaluation of anti-angiogenesis therapy.

Method: 99mTc-EC-endostatin was prepared by conjugating ethylenedicysteine (EC) to endostatin, followed by adding pertechnetate and tin chloride. Radiochemical purity was > 95%. In vitro cell viability, affinity and TUNEL assays were performed. Tissue distribution and planar imaging of radiolabeled endostatin were determined in tumor-bearing rats. To assess anti-angiogenic treatment response, rats were treated with endostatin, paclitaxel and saline, followed by imaging with 99mTc-EC-endostatin. Tumor response to endostatin therapy in tumor-bearing animal models was assessed by correlating tumor uptake dose with microvessel density, VEGF, bFGF and IL-8 expression during endostatin therapy.

Results: In vitro cell viability and TUNEL assays indicated no marked difference between EC-endostatin and endostatin. Cellular uptake assay suggests that endostatin binds to endostatin receptor. Biodistribution of 99mTc-EC-endostatin in tumor-bearing rats showed increased tumor-to-tissue count density ratios as a function of time. Tumor uptake (%ID/g) of 99mTc-EC-endostatin was 0.2-0.5. Planar images confirmed that the tumors could be visualized clearly with 99mTc-EC-endostatin. The optimal time for imaging using radiolabeled endostatin was 2 hrs. 99mTc-EC-endostatin could assess treatment response. There was a correlation between tumor uptake and cellular targets expression.

Conclusion: The results indicate that it is feasible to use 99mTc-EC-endostatin to assess efficiency of anti-angiogenesis therapy.

Publication types

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

MeSH terms

  • Angiogenesis Inhibitors / pharmacokinetics
  • Angiogenesis Inhibitors / therapeutic use*
  • Animals
  • Antineoplastic Combined Chemotherapy Protocols / pharmacology
  • Apoptosis / drug effects
  • Apoptosis / radiation effects
  • Collagen / pharmacokinetics
  • Collagen / therapeutic use*
  • Cysteine / analogs & derivatives*
  • Cysteine / pharmacokinetics
  • Cysteine / therapeutic use*
  • Endostatins
  • Endothelial Growth Factors / metabolism
  • Female
  • Fibroblast Growth Factor 2 / metabolism
  • In Situ Nick-End Labeling
  • Intercellular Signaling Peptides and Proteins / metabolism
  • Interleukin-8 / metabolism
  • Lymphokines / metabolism
  • Mammary Neoplasms, Experimental / blood supply*
  • Mammary Neoplasms, Experimental / diagnostic imaging
  • Neovascularization, Pathologic / drug therapy*
  • Neovascularization, Pathologic / metabolism
  • Paclitaxel / pharmacology
  • Peptide Fragments / pharmacokinetics
  • Peptide Fragments / therapeutic use*
  • Radionuclide Imaging
  • Rats
  • Rats, Inbred F344
  • Technetium / pharmacokinetics
  • Technetium / therapeutic use
  • Tumor Cells, Cultured / drug effects
  • Tumor Cells, Cultured / metabolism
  • Tumor Cells, Cultured / radiation effects
  • Vascular Endothelial Growth Factor A
  • Vascular Endothelial Growth Factors


  • Angiogenesis Inhibitors
  • Endostatins
  • Endothelial Growth Factors
  • Intercellular Signaling Peptides and Proteins
  • Interleukin-8
  • Lymphokines
  • Peptide Fragments
  • Vascular Endothelial Growth Factor A
  • Vascular Endothelial Growth Factors
  • ethylene dicysteine
  • Fibroblast Growth Factor 2
  • Technetium
  • Collagen
  • Cysteine
  • Paclitaxel