分次放射治疗的生物学基础PPT.ppt

放射敏感性: 氧效应 放射敏感性 和 氧分压 1.0 2.0 3.0 0 20 40 60 80 155 760 2280 Air 100% O2 HBO (3 ATA) Venous Blood Relative Radiosensitivity Oxygen tension (mmHg) (Rockwell et al.) Half maximum sensitivity = 3 mmHg or 0.5% O2 Kirkpatrick JP, et al. Intl. J. Rad. Oncol. Biol. Phys. 59:822, 2004 CHO Cells Relative Radiosensitivity 肿瘤乏氧生物学 Hypoxic Region Blood Vessel O2 / Drug Concentration Gene/Protein Regulation Increased Glycolysis Increased Angiogenesis Increased Genomic Instability Selection of Apoptosis Resistance Chemo/Radio-therapy Resistance 肿瘤中的乏氧细胞 Evans and Koch, 01 乏氧 (EF5, Red) 和 增殖 (Ki67, Green) 氧增强比Oxygen Enhancement Ratio (OER) The ratio of HYPOXIC to AEROBIC IR doses needed to achieve the SAME biological effects. OER = D0 (hypoxic) D0 (aerobic) 细胞敏感性与OER Resistant Cells High OER Sensitive Cells Low OER 射线质与OER X-rays neutrons a-particles LET = 2.0 LET and OER 60 氧效应是时间依赖性的 1. O2 needs not to be present DURING radiation 2. O2 has to be present WITHIN milliseconds after radiation Radiation Ion pairs Free Radicals T = 10-10 sec T = 10-5 sec (0.01 msec) Time delay is determined by lifetime of free radicals 细胞周期中OER变化小 S phase (OER = 2.8-2.9) G2/M phase (OER = 2.3-2.4) G1 phase OER remains unchanged for ALL dose levels in a given phase of cell cycle. 氧效应-小结 Presence of Oxygen dramatically influences biological effect OER (dose ratio with/without oxygen for same effect) for x-rays ~2 at 50 Rad and increases to ~3 at 200 Rad OER decreases with increasing LET, reaching 1 for high LET Oxygen must be present during exposure for an effect Oxygen “fixes”(makes permanent) otherwise reparable indirect action damage ( no Oxygen effect for direct action damage). Small quantities (0.5%) sufficient for sensitivity midway between hypoxia and full oxygenation) Reoxygenation: cells hypoxic during irradiation become oxygenated afterwards. Amount and speed of reoxygenation varies widely for different tumors 相对生物效应Retalive Biological Effection (RBE) RBE – Re