Fu Guifeng, Zhu Lei, Yang Kai, Zhuang Rongqiang, Xie Jin, Zhang Fan
State Key Laboratory of Molecular Vaccinology and Molecular Diagnostics & Center for Molecular Imaging and Translational Medicine, School of Public Health, Xiamen University , Xiamen, Fujian 361005, China.
Jiangsu Key Laboratory for Carbon-Based Functional Materials and Devices, Institute of Functional Nano and Soft Materials Laboratory (FUNSOM), Soochow University , Suzhou, Jiangsu 215123, China.
ACS Appl Mater Interfaces. 2016 Mar 2;8(8):5137-47. doi: 10.1021/acsami.5b11936. Epub 2016 Feb 17.
Photothermal therapy (PTT) as a relatively new cancer treatment method has attracted worldwide attention. Previous research on PTT has focused on its therapy efficiency and selectivity. The early prognosis of PTT, which is pivotal for the assessment of the treatment and the therapy stratification, however, has been rarely studied. In the present study, we investigated diffusion-weighted magnetic resonance imaging (DW-MRI) as a tool for therapy monitoring and early prognosis of PTT. To this end, we injected PEGylated graphene oxide (GO-PEG) or iron oxide deposited graphene oxide (GO-IONP-PEG) to 4T1 tumor models and irradiated the tumors at different drug-light intervals to induce PTT. For GO-IONP-PEG injected animals, we also included therapy arms where an external magnetic field was applied to the tumors to improve the delivery of the nanoparticle transducers. DW-MRI was performed at different time points after PTT and the tumor apparent diffusion coefficients (ADCs) were analyzed and compared. Our studies show that photothermal agents, magnetic guidance, and drug-light intervals can all affect PTT treatment efficacy. Impressively, ADC value changes at early time points after PTT (less than 48 h) were found to be well-correlated with tumor growth suppression that was apparent days or weeks later. The changes were most sensitive to conditions that can extend the survival for more than 4 weeks, in which cases the 48 h ADC values were increased by more than 80%. These studies demonstrate for the first time that DW-MRI can be an accurate prognosis tool for PTT, suggesting an important role it can play in the future PTT evaluation and clinical translation of the modality.
光热疗法（PTT）作为一种相对较新的癌症治疗方法已引起全球关注。先前关于PTT的研究主要集中在其治疗效率和选择性上。然而，PTT的早期预后对于治疗评估和治疗分层至关重要，但却很少被研究。在本研究中，我们研究了扩散加权磁共振成像（DW-MRI）作为PTT治疗监测和早期预后评估的工具。为此，我们将聚乙二醇化氧化石墨烯（GO-PEG）或氧化铁沉积氧化石墨烯（GO-IONP-PEG）注射到4T1肿瘤模型中，并在不同的药物-光照间隔下对肿瘤进行照射以诱导PTT。对于注射了GO-IONP-PEG的动物，我们还设置了治疗组，对肿瘤施加外部磁场以改善纳米颗粒换能器的递送。在PTT后的不同时间点进行DW-MRI检查，并分析和比较肿瘤表观扩散系数（ADC）。我们的研究表明，光热剂、磁引导和药物-光照间隔都会影响PTT的治疗效果。令人印象深刻的是，发现PTT后早期时间点（小于48小时）的ADC值变化与数天或数周后明显的肿瘤生长抑制密切相关。这些变化对能够延长生存期超过4周的情况最为敏感，在这些情况下，48小时的ADC值增加超过80%。这些研究首次证明DW-MRI可以作为PTT的准确预后评估工具，表明其在未来PTT评估和该治疗方式的临床转化中可以发挥重要作用。
