Utility of apoptotic imaging to evaluate sensitivity of anti-tumoral drugs

2001 Fiscal Year Final Research Report Summary

• Project/Area Number: 12670896
• Research Category: Grant-in-Aid for Scientific Research (C)
• Allocation Type: Single-year Grants
• Section: 一般
• Research Field: Radiation science
• Research Institution: Kyoto Prefectural University of Medicine (KPUM)
• Principal Investigator: USHIJIMA Yo Kyoto Prefectural University of Medicine, Radiology, Assistant professor, 医学部, 助手 (20275209)
• Co-Investigator(Kenkyū-buntansha): NISHIMURA Tsunehiko Kyoto Prefectural University of Medicine, Radiology, professor, 医学部, 教授 (70237733) ; OHTSUKI Katsuichi Kyoto Prefectural University of Medicine, Medicine, Assistant professor, 医学部, 助手 (90254325)
• Project Period (FY): 2000 – 2001
• Keywords: Apoptosis / ^<99 m>Tc-AnnexinV / Tumor

Research Abstract

1. Anti-mouse Fas monoclonal antibody (10 mg/mouse) was administered to normal BALB/e mice and followed by 99mTe-hydrazinonicotinamide (HYNIC) - Annexin V-(HAV) (100 mCi/mouse) administration 2.5 hours later. Gamma camera imaging was performed one hour after 99mTc-HAV administration. The anti-Fas antibody-injected mice showed an approximately four times higher % injected dose (%ID) than the anti-Fas antibody-uninjected controls, and gamma camera imaging also showed marked accumulation in the liver. However, the anti-Fas antibody-injected mice showed a reduction in accumulation of 99mTc-HAV in the kidney to approximately one third the level in the controls.
2. We examined the ability of 99mTc-HAV to detect dexamethasone (DEX)-induced apoptosis in mouse thymocytes. The reduced viability and the DNA ladder formation indicated that DEX-treated mice had a markedly reduced %ID uptake of 99mTOHAV in spite of the presence of apoptosis, suggesting that 99mTC-HAV cannot be used to image mild apoptosis, such as DEX-induced thymocyte apoptosis.
3. To examine the antitumor effect of vindesine (VDS), we administered YDS intraperitoneally, estimated tumor weight by caliper measurement, and calculated the inhibition rate. While tumor weight had increased 12 hour or more after administration in the control group (saline-treated group), tumor weight remained constant till 72 hours after administration and a tended to increase later in the VDS group. Electrophoresis of DNA isolated from the tumor cells at 12, 24, and 48 hours demonstrated the typical ladder pattern in the VDS group, whereas no ladder pattern was observed at any time in the controls. Assessment of the occurrence of apoptosis in the tumor by terminal deoxynucleotidyl transferase-mediated deoxyuridine triphosphate nick end-labeling (TUNEL) assay at 24 and 48 hours after administration of VDS revealed approximately 5 % TUNEL-positive cells at 24 hours and about 30 % at 48 hours.