Feldman Lisa A, Fabre Marie-Sophie, Grasso Carole, Reid Dana, Broaddus William C, Lanza Gregory M, Spiess Bruce D, Garbow Joel R, McConnell Melanie J, Herst Patries M
Department of Neurosurgery, Virginia Commonwealth University, Richmond, VA United States of America.
Malaghan Institute of Medical Research, Wellington, New Zealand.
PLoS One. 2017 Sep 5;12(9):e0184250. doi: 10.1371/journal.pone.0184250. eCollection 2017.
Tumour hypoxia limits the effectiveness of radiation therapy. Delivering normobaric or hyperbaric oxygen therapy elevates pO2 in both tumour and normal brain tissue. However, pO2 levels return to baseline within 15 minutes of stopping therapy.
To investigate the effect of perfluorocarbon (PFC) emulsions on hypoxia in subcutaneous and intracranial mouse gliomas and their radiosensitising effect in orthotopic gliomas in mice breathing carbogen (95%O2 and 5%CO2).
PFC emulsions completely abrogated hypoxia in both subcutaneous and intracranial GL261 models and conferred a significant survival advantage orthotopically (Mantel Cox: p = 0.048) in carbogen breathing mice injected intravenously (IV) with PFC emulsions before radiation versus mice receiving radiation alone. Carbogen alone decreased hypoxia levels substantially and conferred a smaller but not statistically significant survival advantage over and above radiation alone.
IV injections of PFC emulsions followed by 1h carbogen breathing, radiosensitises GL261 intracranial tumors.
肿瘤缺氧限制了放射治疗的效果。给予常压或高压氧治疗可提高肿瘤组织和正常脑组织中的氧分压(pO2)。然而,停止治疗后15分钟内,pO2水平会恢复到基线。
研究全氟碳(PFC)乳剂对皮下和颅内小鼠胶质瘤缺氧的影响及其对吸入卡波金(95%氧气和5%二氧化碳)的小鼠原位胶质瘤的放射增敏作用。
PFC乳剂完全消除了皮下和颅内GL261模型中的缺氧情况,并且在放射前经静脉注射(IV)PFC乳剂的吸入卡波金的小鼠中,与单纯接受放射治疗的小鼠相比,原位肿瘤具有显著的生存优势(Mantel Cox检验:p = 0.048)。单独使用卡波金可大幅降低缺氧水平,且与单纯放射治疗相比,具有较小但无统计学意义的生存优势。
静脉注射PFC乳剂后进行1小时的卡波金吸入,可使GL261颅内肿瘤产生放射增敏作用。