Assessment of antiangiogenic effect using 99mTc-EC-endostatin

• Published in: Cancer biotherapy & radiopharmaceuticals Vol. 17; no. 2; pp. 233 - 246
• Main Authors: YANG, David J, KIM, Kil-Dong, BRYANT, Jerry L, HERBST, Roy, ABBRUZZES, James, KIM, E. Edmund, PODOLOFF, Donald A, SCHECHTER, Naomi R, YU, Dong-Fang, PENG WU, AZHDARINIA, Ali, ROACH, Jennifer S, KALIMI, Saady K, OZAKI, Kaoru, FOGLER, William E
• Format: Journal Article
• Language: English
• Published: Larchmont, NY Liebert 01.04.2002; Mary Ann Liebert, Inc
• Subjects: Angiogenesis Inhibitors - pharmacokinetics; Angiogenesis Inhibitors - therapeutic use; Animals; Antineoplastic agents; Antineoplastic Combined Chemotherapy Protocols - pharmacology; Apoptosis - drug effects; Apoptosis - radiation effects; Biological and medical sciences; Chemotherapy; 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; Medical sciences; Neovascularization, Pathologic - drug therapy; Neovascularization, Pathologic - metabolism; Paclitaxel - pharmacology; Peptide Fragments - pharmacokinetics; Peptide Fragments - therapeutic use; Pharmacology. Drug treatments; 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; Antineoplastic agent; Intravenous administration; Rat; Treatment efficiency; Rodentia; Endostatin; Scintigraphy; Malignant tumor; Mammary gland diseases; Vertebrata; Chemotherapy; Mammalia; Treatment; Animal; Blood vessel; Distribution; Medical imagery; Mammary gland; Antiangiogenic agent; Conjugated compound
• ISSN: 1084-9785; 1557-8852
• DOI: 10.1089/108497802753773856

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 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. 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.