Department of Radiology, Memorial Sloan Kettering Cancer Center, New York, USA.
Department of Neurosurgery, University Hospital Cologne, Cologne, Germany.
Theranostics. 2018 Jan 1;8(3):723-734. doi: 10.7150/thno.20386. eCollection 2018.
Monitoring emerging vascular-targeted photodynamic therapy (VTP) and understanding the time-dynamics of treatment effects remains challenging. We interrogated whether handheld multispectral optoacoustic tomography (MSOT) could noninvasively monitor the effect of VTP using WST11, a vascular-acting photosensitizer, on tumor tissues over time using a renal cell cancer mouse model. We also investigated whether MSOT illumination can induce VTP, to implement a single-modality theranostic approach. Eight BalB/c mice were subcutaneously implanted with murine renal adenocarcinoma cells (RENCA) on the flank. Three weeks later VTP was performed (10 min continuous illumination at 753 nm following intravenous infusion using WST11 or saline as control. Handheld MSOT images were collected prior to VTP administration and subsequently thereafter over the course of the first hour, at 24 and 48 h. Data collected were unmixed for blood oxygen saturation in tissue (SO) based on the spectral signatures of deoxy- and oxygenated hemoglobin. Changes in oxygen saturation over time, relative to baseline, were examined by paired t-test for statistical significance (p < 0.05). In-vivo findings were corroborated by histological analyses of the tumor tissue. MSOT is shown to prominently resolve changes in oxygen saturation in tumors within the first 20 min post WST11-VTP treatment. Within the first hour post-treatment, SO decreased by more than 60% over baseline (p < 0.05), whereas it remained unchanged (p > 0.1) in the sham-treated group. Moreover, unlike in the control group, SO in treated tumors further decreased over the course of 24 to 48 h post-treatment, concomitant with the propagation of profound central tumor necrosis present in histological analysis. We further show that pulsed MSOT illumination can activate WST11 as efficiently as the continuous wave irradiation employed for treatment. Handheld MSOT non-invasively monitored WST11-VTP effects based on the SO signal and detected blood saturation changes within the first 20 min post-treatment. MSOT may potentially serve as a means for both VTP induction and real-time VTP monitoring in a theranostic approach.
监测新兴的血管靶向光动力疗法（VTP）并了解治疗效果的时间动态仍然具有挑战性。我们探讨了手持式多光谱光声断层扫描（MSOT）是否可以使用 WST11（一种血管作用的光敏剂）在肾细胞癌小鼠模型中，随时间推移非侵入性地监测 VTP 的效果。我们还研究了 MSOT 照射是否可以诱导 VTP，以实现单一模式的治疗方法。
8 只 BalB/c 小鼠在侧腹皮下植入了鼠肾腺癌细胞（RENCA）。3 周后进行 VTP（静脉内输注 WST11 或生理盐水作为对照后，连续 10 分钟 753nm 照射）。在 VTP 给药前和给药后 1 小时内、24 小时和 48 小时收集手持式 MSOT 图像。根据脱氧和氧合血红蛋白的光谱特征，对组织中的血氧饱和度（SO）进行无混合数据采集。通过配对 t 检验检查氧饱和度随时间的变化相对于基线的统计学意义（p < 0.05）。体内发现得到肿瘤组织的组织学分析的证实。
MSOT 显示，在 WST11-VTP 治疗后 20 分钟内，可以明显分辨出肿瘤中氧饱和度的变化。在治疗后 1 小时内，SO 比基线下降超过 60%（p < 0.05），而在假处理组中则保持不变（p > 0.1）。此外，与对照组不同，在治疗后 24 至 48 小时内，治疗肿瘤中的 SO 进一步下降，与组织学分析中存在的中央肿瘤坏死的传播相一致。我们进一步表明，与用于治疗的连续波照射相比，脉冲 MSOT 照射可以有效地激活 WST11。
手持式 MSOT 非侵入性地监测基于 SO 信号的 WST11-VTP 效应，并在治疗后 20 分钟内检测到血液饱和度变化。MSOT 可能在治疗方法中作为 VTP 诱导和实时 VTP 监测的手段。
