Wang Ken Kang-Hsin, Cottrell William J, Mitra Soumya, Oseroff Allan R, Foster Thomas H
Department of Physics and Astronomy, University of Rochester, Rochester, New York 14627, USA.
Lasers Surg Med. 2009 Nov;41(9):686-96. doi: 10.1002/lsm.20847.
In a recently completed pilot clinical study at Roswell Park Cancer Institute, patients with superficial basal cell carcinoma (sBCC) received topical application of 20% 5-aminolevulinic acid (ALA) and were irradiated with 633 nm light at 10-150 mW cm(-2). Protoporphyrin IX (PpIX) photobleaching in the lesion and the adjacent perilesion normal margin was monitored by fluorescence spectroscopy. In most cases, the rate of bleaching slowed as treatment progressed, leaving a fraction of the PpIX unbleached despite sustained irradiation. To account for this feature, we hypothesized a decrease in blood flow during ALA-photodynamic therapy (PDT) that reduced the rate of oxygen transported to the tissue and therefore attenuated the photobleaching process. We have performed a detailed analysis of this hypothesis.
STUDY DESIGN/MATERIALS AND METHODS: We used a comprehensive, previously published mathematical model to simulate the effects of therapy-induced blood flow reduction on the measured PpIX photobleaching. This mathematical model of PDT in vivo incorporates a singlet-oxygen-mediated photobleaching mechanism, dynamic unloading of oxygen from hemoglobin, and provides for blood flow velocity changes. It permits simulation of the in vivo photobleaching of PpIX in this patient population over the full range of irradiances and fluences.
The results suggest that the physiological equivalent of discrete blood flow reductions is necessary to simulate successfully the features of the bleaching data over the entire treatment fluence regime. Furthermore, the magnitude of the blood flow changes in the normal tissue margin and lesion for a wide range of irradiances is consistent with a nitric-oxide-mediated mechanism of vasoconstriction.
A detailed numerical study using a comprehensive PDT dosimetry model is consistent with the hypothesis that the observed trends in the in vivo PpIX photobleaching data from patients may be explained on the basis of therapy-induced blood flow reductions at specific fluences.
在罗斯韦尔帕克癌症研究所最近完成的一项试点临床研究中，浅表性基底细胞癌（sBCC）患者局部应用20%的5-氨基酮戊酸（ALA），并接受波长为633 nm、光强为10 - 150 mW/cm²的光照。通过荧光光谱法监测病变部位及相邻病变周围正常边缘区域的原卟啉IX（PpIX）光漂白情况。在大多数情况下，随着治疗的进行，漂白速率减缓，尽管持续照射，仍有一部分PpIX未被漂白。为解释这一现象，我们推测在ALA光动力疗法（PDT）过程中血流减少，降低了氧气输送到组织的速率，从而减弱了光漂白过程。我们对这一假设进行了详细分析。
研究设计/材料与方法：我们使用一个全面的、先前已发表的数学模型来模拟治疗引起的血流减少对所测PpIX光漂白的影响。这个体内PDT数学模型纳入了单线态氧介导的光漂白机制、血红蛋白对氧气的动态卸载，并考虑了血流速度变化。它能够模拟该患者群体在整个辐照度和fluence范围内PpIX的体内光漂白情况。
结果表明，离散性血流减少的生理等效情况对于成功模拟整个治疗fluence范围内的漂白数据特征是必要的。此外，在广泛的辐照度范围内，正常组织边缘和病变部位血流变化的幅度与一氧化氮介导的血管收缩机制一致。
使用全面的PDT剂量测定模型进行的详细数值研究与以下假设一致，即患者体内PpIX光漂白数据中观察到的趋势可以基于特定fluence下治疗引起的血流减少来解释。
