OxyChip embedded with radio-opaque gold nanoparticles for anatomic registration and oximetry in tissues.

Abstract

Electron paramagnetic resonance oximetry using the OxyChip as an implantable oxygen sensor can directly and repeatedly measure tissue oxygen levels. A phase I, first-in-human clinical study has established the safety and feasibility of using OxyChip for reliable and repeated measurements of oxygen levels in a variety of tumors and treatment regimens. A limitation in these studies is the inability to easily locate and identify the implanted probes in the tissue, particularly in the long term, thus limiting spatial/anatomical registration of the implant for proper interpretation of the oxygen data. In this study, we have developed and evaluated an enhanced oxygen-sensing probe embedded with gold nanoparticles (GNP), called the OxyChip-GNP, to enable visualization of the sensor using routine clinical imaging modalities. In vitro characterization, imaging, and histopathology studies were carried out using tissue phantoms, excised tissues, and in vivo animal models (mice and rats). The results demonstrated a substantial enhancement of ultrasound and CT contrast using the OxyChip-GNP without compromising its electron paramagnetic resonance and oxygen-sensing properties or biocompatibility. The OxyChips embedded with gold nanoparticles (OxyChip-GNP) can be readily identified in soft tissues using standard clinical imaging modalities such as CT, cone beam-CT, or ultrasound imaging while maintaining its capability to make repeated in vivo measurements of tissue oxygen levels over the long term. This unique capability of the OxyChip-GNP facilitates precisely localized in vivo oxygen measurements in the clinical setting.