Folz Jeff, Jo Janggun, Gonzalez Maria E, Eido Ahmad, Zhai Tianqu, Caruso Roberta, Kleer Celina G, Wang Xueding, Kopelman Raoul
Department of Chemistry, University of Michigan, Ann Arbor, MI 48109, USA.
Department of Biomedical Engineering, University of Michigan, Ann Arbor, MI 48109, USA.
J Photochem Photobiol. 2024 Jun;21. doi: 10.1016/j.jpap.2024.100241. Epub 2024 Apr 27.
Early detection and diagnosis of cancer is critical for achieving positive therapeutic outcomes. Biomarkers that can provide clinicians with clues to the outcome of a given therapeutic course are highly desired. Oxygen is a small molecule that is nearly universally present in biological tissues and plays a critical role in the effectiveness of radiotherapies by reacting with DNA radicals and subsequently impairing cellular repair of double strand breaks.Techniques for measuring oxygen in biological tissues often use blood oxygen saturation to approximate the oxygen partial pressure in surrounding tissues despite the complex, nonlinear, and dynamic relationship between these two separate oxygen populations.
We combined a directly oxygen-sensitive, tumor-targeted, chemical contrast nanoelement with the photoacoustic lifetime-based (PALT) oxygen imaging technique to obtain image maps of oxygen in breast cancer tumors in vivo. The oxygen levels of patient-derived xenografts in a mouse model were characterized before and after a course of radiotherapy.
We show that, independent of tumor size, radiotherapy induced an increase in the overall oxygenation levels of the tumor. Further, this increase in the oxygenation of the tumor significantly correlated with a positive response to radiotherapy, as demonstrated by a reduction in tumor volume over the twenty-day monitoring period following therapy and histological staining.
Our PALT imaging presented here is simple, fast, and non-invasive. Facilized by the PALT approach, imaging of tumor reoxygenation may be utilized as a simple, early indicator for evaluating cancer response to radiotherapy. Further characterization of the reoxygenation degree, temporal onset, and possible theragnostic implications are warranted.
癌症的早期检测和诊断对于实现积极的治疗结果至关重要。非常需要能够为临床医生提供给定治疗过程结果线索的生物标志物。氧气是一种几乎普遍存在于生物组织中的小分子，通过与DNA自由基反应并随后损害双链断裂的细胞修复，在放射治疗的有效性中起关键作用。尽管这两个独立的氧群体之间存在复杂、非线性和动态的关系，但测量生物组织中氧气的技术通常使用血氧饱和度来近似周围组织中的氧分压。
我们将一种对氧气直接敏感、靶向肿瘤的化学对比纳米元素与基于光声寿命（PALT）的氧成像技术相结合，以获得体内乳腺癌肿瘤中氧气的图像图谱。在放疗疗程前后对小鼠模型中患者来源的异种移植瘤的氧水平进行了表征。
我们表明，与肿瘤大小无关，放疗导致肿瘤整体氧合水平升高。此外，肿瘤氧合的这种增加与放疗的阳性反应显著相关，这通过治疗后二十天监测期内肿瘤体积的减小和组织学染色得以证明。
我们在此展示的PALT成像简单、快速且无创。在PALT方法的帮助下，肿瘤再氧合成像可作为评估癌症对放疗反应的简单早期指标。有必要进一步表征再氧合程度、时间 onset以及可能的治疗诊断意义。 （注：原文中“temporal onset”不太明确准确含义，这里保留原文未准确翻译）
