Significance: The necessity to use exogenous probes for optical oxygen measurements in radiotherapy poses challenges for clinical applications. Options for implantable probe biotechnology need to be improved to alleviate toxicity concerns in human use and facilitate translation to clinical trial use. Aim: To develop an implantable oxygen sensor containing a phosphorescent oxygen probe such that the overall administered dose of the probe would be below the Federal Drug Administration (FDA)-prescribed microdose level, and the sensor would provide local high-intensity signal for longitudinal measurements of tissue pO2. Approach: PtG4, an oxygen quenched dendritic molecule, was mixed into an agarose matrix at 100 μM concentration, allowing for local injection into tumors at the total dose of 10 nmol per animal, forming a gel at the site of injection. Cherenkov-excited luminescence imaging (CELI) was used to acquire the phosphorescence and provide intratumoral pO2. Results: Although PtG4 does not form covalent bonds with agarose and gradually leaches out into the surrounding tissue, its retention time within the gel was sufficiently long to demonstrate the capability to measure intratumoral pO2 with the implantable gel sensors. The sensor’s performance was first evaluated in vitro in tissue simulation phantoms, and then the sensor was used to measure changes in oxygen in MDA-MB-231 tumors during hypofractionated radiotherapy. Conclusions: Our study demonstrates that implantable oxygen sensors in combination with CELI present a promising approach for quantifying oxygen changes during the course of radiation therapy and thus for evaluating the tumor response to radiation. By improving the design of the gel–probe composition in order to prevent leaching of the probe into the tissue, biosensors can be created that should allow longitudinal oxygen measurements in tumors by means of CELI while using FDA-compliant microdose levels of the probe and thus lowering toxicity concerns.

中文翻译：

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用于放疗期间肿瘤 pO2 局部切伦科夫激发发光成像的植入式传感器

意义：在放射治疗中使用外源性探头进行光学氧测量的必要性给临床应用带来了挑战。需要改进植入式探针生物技术的选择，以减轻人类使用中的毒性问题并促进转化为临床试验使用。目标：开发一种包含磷光氧探针的植入式氧传感器，使探针的总给药剂量低于联邦药物管理局 (FDA) 规定的微剂量水平，并且传感器将为纵向测量提供局部高强度信号组织 pO2。方法：PtG4，一种氧淬灭的树突分子，以 100 μM 的浓度混合到琼脂糖基质中，允许以每只动物 10 nmol 的总剂量局部注射到肿瘤中，在注射部位形成凝胶。Cherenkov 激发的发光成像 (CELI) 用于获取磷光并提供瘤内 pO2。结果：虽然 PtG4 不与琼脂糖形成共价键并逐渐渗出到周围组织中，但它在凝胶中的保留时间足够长，可以证明使用植入式凝胶传感器测量肿瘤内 pO2 的能力。该传感器的性能首先在组织模拟体模中进行体外评估，然后该传感器用于测量大分割放疗期间 MDA-MB-231 肿瘤中的氧气变化。结论：我们的研究表明，植入式氧传感器与 CELI 相结合，为量化放射治疗过程中的氧变化提供了一种有前景的方法，从而评估肿瘤对放射的反应。