Assessment of antiangiogenic effect using 99mTc-EC-endostatin

David J. Yang, Kil Dong Kim, Naomi R. Schechter, Dong Fang Yu, Peng Wu, Ali Azhdarinia, Jennifer S. Roach, Saady K. Kalimi, Kaoru Ozaki, William E. Fogler, Jerry L. Bryant, Roy Herbst, James Abbruzzes, E. Edmund Kim, Donald A. Podoloff

Research output: Contribution to journalArticle

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Abstract

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.

Original languageEnglish (US)
Pages (from-to)233-246
Number of pages14
JournalCancer Biotherapy and Radiopharmaceuticals
Volume17
Issue number2
DOIs
StatePublished - 2002

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Endostatins
Neoplasms
In Situ Nick-End Labeling
Cell Survival
Sodium Pertechnetate Tc 99m

Keywords

  • Antiangiogenesis
  • Biodistribution
  • Imaging

ASJC Scopus subject areas

  • Oncology
  • Radiology Nuclear Medicine and imaging
  • Pharmacology
  • Cancer Research

Cite this

Yang, D. J., Kim, K. D., Schechter, N. R., Yu, D. F., Wu, P., Azhdarinia, A., ... Podoloff, D. A. (2002). Assessment of antiangiogenic effect using 99mTc-EC-endostatin. Cancer Biotherapy and Radiopharmaceuticals, 17(2), 233-246. https://doi.org/10.1089/108497802753773856

Assessment of antiangiogenic effect using 99mTc-EC-endostatin. / Yang, David J.; Kim, Kil Dong; Schechter, Naomi R.; Yu, Dong Fang; Wu, Peng; Azhdarinia, Ali; Roach, Jennifer S.; Kalimi, Saady K.; Ozaki, Kaoru; Fogler, William E.; Bryant, Jerry L.; Herbst, Roy; Abbruzzes, James; Kim, E. Edmund; Podoloff, Donald A.

In: Cancer Biotherapy and Radiopharmaceuticals, Vol. 17, No. 2, 2002, p. 233-246.

Research output: Contribution to journalArticle

Yang, DJ, Kim, KD, Schechter, NR, Yu, DF, Wu, P, Azhdarinia, A, Roach, JS, Kalimi, SK, Ozaki, K, Fogler, WE, Bryant, JL, Herbst, R, Abbruzzes, J, Kim, EE & Podoloff, DA 2002, 'Assessment of antiangiogenic effect using 99mTc-EC-endostatin', Cancer Biotherapy and Radiopharmaceuticals, vol. 17, no. 2, pp. 233-246. https://doi.org/10.1089/108497802753773856
Yang, David J. ; Kim, Kil Dong ; Schechter, Naomi R. ; Yu, Dong Fang ; Wu, Peng ; Azhdarinia, Ali ; Roach, Jennifer S. ; Kalimi, Saady K. ; Ozaki, Kaoru ; Fogler, William E. ; Bryant, Jerry L. ; Herbst, Roy ; Abbruzzes, James ; Kim, E. Edmund ; Podoloff, Donald A. / Assessment of antiangiogenic effect using 99mTc-EC-endostatin. In: Cancer Biotherapy and Radiopharmaceuticals. 2002 ; Vol. 17, No. 2. pp. 233-246.
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