Yu Guoqiang, Durduran Turgut, Zhou Chao, Wang Hsing-Wen, Putt Mary E, Saunders H Mark, Sehgal Chandra M, Glatstein Eli, Yodh Arjun G, Busch Theresa M
Department of Physics and Astronomy, School of Arts and Sciences, University of Pennsylvania, Philadelphia, Pennsylvania 19104, USA.
Clin Cancer Res. 2005 May 1;11(9):3543-52. doi: 10.1158/1078-0432.CCR-04-2582.
To monitor tumor blood flow noninvasively during photodynamic therapy (PDT) and to correlate flow responses with therapeutic efficacy.
Diffuse correlation spectroscopy (DCS) was used to measure blood flow continuously in radiation-induced fibrosarcoma murine tumors during Photofrin (5 mg/kg)/PDT (75 mW/cm2, 135 J/cm2). Relative blood flow (rBF; i.e., normalized to preillumination values) was compared with tumor perfusion as determined by power Doppler ultrasound and was correlated with treatment durability, defined as the time of tumor growth to a volume of 400 mm3. Broadband diffuse reflectance spectroscopy concurrently quantified tumor hemoglobin oxygen saturation (SO2).
DCS and power Doppler ultrasound measured similar flow decreases in animals treated with identical protocols. DCS measurement of rBF during PDT revealed a series of PDT-induced peaks and declines dominated by an initial steep increase (average +/- SE: 168.1 +/- 39.5%) and subsequent decrease (59.2 +/- 29.1%). The duration (interval time; range, 2.2-15.6 minutes) and slope (flow reduction rate; range, 4.4 -45.8% minute(-1)) of the decrease correlated significantly (P = 0.0001 and 0.0002, r2= 0.79 and 0.67, respectively) with treatment durability. A positive, significant (P = 0.016, r2= 0.50) association between interval time and time-to-400 mm3 was also detected in animals with depressed pre-PDT blood flow due to hydralazine administration. At 3 hours after PDT, rBF and SO2 were predictive (P < or = 0.015) of treatment durability.
These data suggest a role for DCS in real-time monitoring of PDT vascular response as an indicator of treatment efficacy.
在光动力疗法（PDT）期间无创监测肿瘤血流，并将血流反应与治疗效果相关联。
在使用Photofrin（5mg/kg）/PDT（75mW/cm²，135J/cm²）治疗期间，采用扩散相关光谱法（DCS）连续测量辐射诱导的纤维肉瘤小鼠肿瘤中的血流。将相对血流（rBF；即相对于光照前值进行归一化）与通过功率多普勒超声测定的肿瘤灌注进行比较，并与治疗持久性相关联，治疗持久性定义为肿瘤生长至400mm³体积的时间。宽带漫反射光谱法同时定量肿瘤血红蛋白氧饱和度（SO₂）。
在采用相同方案治疗的动物中，DCS和功率多普勒超声测量到相似的血流减少。PDT期间rBF的DCS测量显示出一系列由PDT诱导的峰值和下降，主要由最初的急剧增加（平均±标准误：168.1±39.5%）和随后的减少（59.2±29.1%）主导。下降的持续时间（间隔时间；范围，2.2 - 15.6分钟）和斜率（血流减少率；范围，4.4 - 45.8%分钟⁻¹）与治疗持久性显著相关（P = 0.0001和0.0002，r²分别为0.79和0.67）。在因服用肼苯哒嗪导致PDT前血流降低的动物中，还检测到间隔时间与达到400mm³的时间之间存在正的、显著的关联（P = 0.016，r² = 0.50）。在PDT后3小时，rBF和SO₂可预测（P≤0.015）治疗持久性。
这些数据表明DCS在实时监测PDT血管反应作为治疗效果指标方面具有作用。
