1. Assessment of Antiangiogenic Effect Using99mTc-EC-Endostatin
- Author
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Kaoru Ozaki, William E. Fogler, Jerry Bryant, Jennifer S. Roach, Ali Azhdarinia, James Abbruzzes, Dong Fang Yu, Kil Dong Kim, E. Edmund Kim, Donald A. Podoloff, Naomi R. Schechter, Roy S. Herbst, David J. Yang, Saady Kohanim Kalimi, and Peng Wu
- Subjects
Vascular Endothelial Growth Factor A ,Cancer Research ,Biodistribution ,Pathology ,medicine.medical_specialty ,Paclitaxel ,medicine.medical_treatment ,Angiogenesis Inhibitors ,Apoptosis ,Endothelial Growth Factors ,macromolecular substances ,Pharmacology ,chemistry.chemical_compound ,Antineoplastic Combined Chemotherapy Protocols ,In Situ Nick-End Labeling ,Tumor Cells, Cultured ,Animals ,Medicine ,Distribution (pharmacology) ,Radiology, Nuclear Medicine and imaging ,Cysteine ,Viability assay ,Radionuclide Imaging ,Lymphokines ,Chemotherapy ,TUNEL assay ,Neovascularization, Pathologic ,Vascular Endothelial Growth Factors ,business.industry ,Interleukin-8 ,Mammary Neoplasms, Experimental ,Technetium ,General Medicine ,Peptide Fragments ,Rats, Inbred F344 ,In vitro ,Endostatins ,Rats ,Oncology ,chemistry ,cardiovascular system ,Intercellular Signaling Peptides and Proteins ,Female ,Fibroblast Growth Factor 2 ,Collagen ,Endostatin ,business - Abstract
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.99mTc-EC-endostatin was prepared by conjugating ethylenedicysteine (EC) to endostatin, followed by adding pertechnetate and tin chloride. Radiochemical purity was95%. 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.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.The results indicate that it is feasible to use 99mTc-EC-endostatin to assess efficiency of anti-angiogenesis therapy.
- Published
- 2002