Re-188 in vitro, in vivo treatment effect of SD-rat hepatoma

• Main Authors: SHIH, YING-HSIA, 施映霞
• Other Authors: CHEN, JIAN-CHYI
• Format: Others
• Language: zh-TW
• Published: 2009
• Online Access: http://ndltd.ncl.edu.tw/handle/59800698263910597607

碩士 === 南台科技大學 === 生物科技系 === 97 === Background/Aims Hepatoma is the second common cause of cancer death in Taiwan, and its treatment is still far from satisfactory. 188Rhenium (188Re) is a newly developed radioisotope that has short half life, high energy of β-ray and low amount of γ-ray. It can kill liver tumor cells and is convenient for scintigraphy. We inject 188Re into hepatomas in an animal model to evaluate the radioactivities and drug delivery system for the potential clinical applications. Materials and methods The first part of the study is to select N1-S1 cells that can be transplanted to Sprague-Dawley (SD) rats to form a stable hepatoma model. The second part is to evaluate the cancer response to 188Re ECD/lipiodol. After the injection, we check tissue reaction weekly by pathology studies, including hematoxylin and eosin staining, and TUNEL staining. The third part is the pharmacodynamics and pharmacokinetics of 188Re formulae. The fourth part is treatment evaluations on hepatoma transplanted SD-rat models using 188Re ECD/lipiodol, 188Re ECD/lipiodol in a hydrogel delivery system, or normal saline injections. The comparison is based on survival and tissue pathology studies. Results After primary selection, N1-S1 cells become more tumorigenic, as F2>F1>F0; while the tumorigenicity decrease if the cells are passed more than 20 generations, as some of transplanted tumors can disappear spontaneously. The apoptosis of cells were most abundant in 7 days; then, decreased gradually. Pharmacodynamic study shows that the tumor and liver have the highest levels of radioactivities, and 188Re is secreted mostly from urinary system. Survival analysis shows 188Re ECD/Lipiodol group compared with normal saline group have the most significance difference. The thermosensitive hydrogel has improved the delivery of radioactivities, but has some difficulty in injections, which results little improvement of treatment effects overall. Discussion/conclusions Primary selection of cancer cells can improve tumorigenicity, but too many passes of generation can decrease the stability of tumor model. 188Re ECD/lipiodol has good profile for local injection, as it stays well in the tumors. Our animal experiments also validate the potential usefulness of 188Re ECD/lipiodol to treat hepatoma, judging from survival curves and the pathology studies. We expect that 188Re can be used clinically in the near future.