Oxygen is an important biomarker in cancer biology studies. Tumor hypoxia is one of the most important factors that regulate tumor growth, development, aggressiveness, metastasis and affects treatment outcome. Tumor hypoxia is spatially heterogeneous. Despite the clear importance of tumor oxygenation, most scientists studying tumor hypoxia or oxygen kinetics still rely on two-dimensional cell biology techniques. Most radiation resistance studies are performed in cell cultures or in vivo/in vitro systems where tumors are radiated in situ and tumor cells subsequently explanted, cultured, and studied for survival. Absence of reliable oxygen imaging instrument capable, with sufficient spatial and temporal resolution, of imaging hypoxia in tumor's volume is a challenge for the research field.
We report the construction of the first commercial preclinical oxygen imager, JIVA-25, based on electron paramagnetic resonance oxygen imaging (EPROI). EPROI is a non-invasive oxygen mapping method with high precision and absolute accuracy (1). EPR detects unpaired electron spins subjected to the constant uniform magnetic field by manipulating them using radio-frequency electromagnetic radiation. EPROI uses an injectable non-toxic soluble contrast agent, trityl (OX063/OX063-D24) for obtaining oxygen maps in tumor models. EPROI was used recently for the first demonstration of oxygen guided radiation therapy in a mouse model of tumor (2).
JIVA-25 is a compact 25 mT EPROI instrument suitable for in vitro and small animal in vivo oxygen mapping in tumor models of mice and rats. JIVA-25 provides pO2 maps with a high spatial resolution (up to 0.5 mm), high pO2 resolution (1-3 torr), and high temporal resolution (1-10 min). Currently, the instrument is being tested for its efficacy to provide tumor treatment in mouse model at two locations, Duke Cancer Institute and the University of Chicago. Further development to improve the spatial resolution using NCI developed single point imaging (SPI) is underway using NCI funded SBIR Phase II project. Overall, we expect that JIVA-25 will be a unique tool in helping scientists understand tumor oxygenation, perform efficient tumor treatment studies, and drug development.
Acknowledgement: We acknowledge support from NIH/NCI R43CA224840, NIH/NCI R44CA224840, NSF 1819583, and JDRF 3-SRA-2020-883-M-B.
1. Epel B, Kotecha M, Halpern HJ. In vivo preclinical cancer and tissue engineering applications of absolute oxygen imaging using pulse EPR. J Magn Reson. 2017;280:149-57. doi: 10.1016/j.jmr.2017.04.017. PubMed PMID: 28552587.
2. Epel B, Maggio MC, Barth ED, Miller RC, Pelizzari CA, Krzykawska-Serda M, Sundramoorthy SV, Aydogan B, Weichselbaum RR, Tormyshev VM, Halpern HJ. Oxygen-guided radiation therapy. Int J Radiat Oncol Biol Phys. 2019;103(4):977-84. doi: 10.1016/j.ijrobp.2018.10.041. PubMed PMID: 30414912.
Citation Format: Boris Epel, Howard Halpern, Mrignaayni Kotecha. Preclinical oxygen imager for cancer oxygenation studies [abstract]. In: Proceedings of the Annual Meeting of the American Association for Cancer Research 2020; 2020 Apr 27-28 and Jun 22-24. Philadelphia (PA): AACR; Cancer Res 2020;80(16 Suppl):Abstract nr 1646.