使用人体大小的脉冲电子顺磁共振成像仪对兔肿瘤进行氧气成像。
Oxygen Imaging of a Rabbit Tumor Using a Human-Sized Pulse Electron Paramagnetic Resonance Imager.
发表日期:2023 Sep 15
作者:
Boris Epel, Navin Viswakarma, Subramanian V Sundramoorthy, Nitin J Pawar, Mrignayani Kotecha
来源:
Cellular & Molecular Immunology
摘要:
肿瘤缺氧的空间异质性是调节肿瘤生长、发展、侵袭性、转移以及影响治疗效果的最重要因素之一。大多数实体肿瘤已知有缺氧或低氧(pO2 ≤10 torr)水平。电子顺磁共振氧成像(EPROI)是一种新兴的氧分布技术。EPROI利用可注射的OX071三苯基自旋探针的弛豫率与局部氧分压(pO2)之间的线性关系。然而,由于仪器尺寸的限制,大多数EPROI研究仅限于实体肿瘤的小鼠模型。本研究的目的是开发一种人体尺寸的9毫特斯拉(250兆赫频率,60厘米孔径)脉冲EPROI仪器,并评估其在兔VX-2肿瘤氧成像中的性能。使用人体尺寸的EPROI仪器和2.25英寸内径容积线圈对一只带有3.2厘米VX-2肿瘤的新西兰白兔进行了成像。动物经受了约8分钟的静脉注射OX071(总容积5.2毫升,浓度72毫摩尔),75分钟后进行肿瘤内注射(总容积120微升,浓度5毫摩尔),并进行了EPROI成像。实验结束后,使用一台9.4特斯拉的临床前磁共振成像系统对肿瘤边界进行了描绘。首次建立并评估了带有60厘米孔径/250兆赫频率的人体尺寸脉冲EPROI仪器的性能,并应用于兔肿瘤氧成像。首次在动物体内利用静脉注射氧敏感的OX071自旋探针。通过静脉注射得到的EPROI图像显示了完整的肿瘤覆盖范围。肿瘤内注射后获得的图像显示肿瘤上叶的局部覆盖,揭示了需要改进肿瘤内注射方案。本研究证明了世界第一台人体尺寸脉冲EPROI仪器的性能。同时也证明,利用系统注射可管理量的自旋探针可以实现较大动物的EPROI。这将使EPROI更接近于在癌症治疗中的临床应用。氧成像是一种平台技术,这里开发的仪器和技术也将对其他临床应用有用。©2023年。作者,独家授权给世界分子影像学会。
Spatial heterogeneity in tumor hypoxia is one of the most important factors regulating tumor growth, development, aggressiveness, metastasis, and affecting treatment outcome. Most solid tumors are known to have hypoxia or low oxygen levels (pO2 ≤10 torr). Electron paramagnetic resonance oxygen imaging (EPROI) is an emerging oxygen mapping technology. EPROI utilizes the linear relationship between the relaxation rates of the injectable OX071 trityl spin probe and the partial oxygen pressure (pO2). However, most of the EPROI studies have been limited to mouse models of solid tumors because of the instrument-size limitations. The purpose of this work was to develop a human-sized 9-mT (250 MHz resonance frequency, 60 cm bore size) pulse EPROI instrument and evaluate its performance with rabbit VX-2 tumor oxygen imaging.A New Zealand white rabbit with a 3.2-cm VX-2 tumor in the calf muscle was imaged using the human-sized EPROI instrument and a 2.25-in. ID volume coil. The animal received a ~8-min intravenous injection of OX071 (5.2 mL total volume at 72 mM concentration) and, after 75 min, an intratumoral injection (120 μL total at 5 mM OX071 concentration) and underwent EPROI. At the end of the experiments, MRI was performed using a preclinical 9.4-T MRI system to outline the tumor boundaries.For the first time, a human-sized pulse EPROI instrument with a 60-cm bore size/250-MHz frequency was built and evaluated using rabbit tumor oxygen imaging. For the first time, the systemic IV injection of the oxygen-sensitive trityl OX071 spin probe was used for an animal of this size. The resulting EPROI image from the IV injection showed complete tumor coverage. The image obtained after intratumoral injection showed localized coverage in the upper lobe of the tumor, demonstrating the need for improved intratumoral injection protocol.This study demonstrates the performance of the world's first human-sized pulse EPROI instrument. It also demonstrates that the EPROI of larger animals can be performed using the systemic injection of a manageable amount of the spin probe. This brings EPROI one step closer to clinical applications in cancer therapies. Oxygen imaging is a platform technology, and the instrument and techniques developed here will also be useful for other clinical applications.© 2023. The Author(s), under exclusive licence to World Molecular Imaging Society.