Development of a PET/EPRI combined imaging system for assessing tumor hypoxia

Abstract

Precise quantitative delineation of tumor hypoxia is essential in radiation therapy treatment planning to improve the treatment efficacy by targeting hypoxic sub-volumes. We developed a combined imaging system of positron emission tomography (PET) and electron para-magnetic resonance imaging (EPRI) of molecular oxygen to investigate the accuracy of PET imaging in assessing tumor hypoxia. The PET/EPRI combined imaging system aims to use EPRI to precisely measure the oxygen partial pressure in tissues. This will evaluate the validity of PET hypoxic tumor imaging by (near) simultaneously acquired EPRI as ground truth. The combined imaging system was constructed by integrating a small animal PET scanner (inner ring diameter 62 mm and axial field of view 25.6 mm) and an EPRI subsystem (field strength 25 mT and resonant frequency 700 MHz). The compatibility between the PET and EPRI subsystems were tested with both phantom and animal imaging. Hypoxic imaging on a tumor mouse model using 18F-fluoromisonidazole radio-tracer was conducted with the developed PET/EPRI system. We report the development and initial imaging results obtained from the PET/EPRI combined imaging system.

Dual-Mode Tumor Imaging Using Probes That Are Responsive to Hypoxia-Induced Pathological Conditions

“…Relatively low spatial resolution and d sensitivity which are common limitations of the reported preclinical scanner po can be overcome using EPR-compatible PET systems with higher resolution and d sensitivity than the reported scanner [287]. Kim and co-workers reported MRI-guided PET/EPRI scanner to probe oxyg centration in hypoxic regions of mice bearing squamous cell carcinoma [288]. T2-w MRI was used as an anatomical reference to delineate the tumor region.…”

“…Trityl spi and 9 were used to acquire EPRI and PET imaging data, respectively. Because o duced environment prevalent in hypoxic tumors, 9 tends to accumulate in hypo Kim and co-workers reported MRI-guided PET/EPRI scanner to probe oxygen concentration in hypoxic regions of mice bearing squamous cell carcinoma [288]. T 2 -weighted MRI was used as an anatomical reference to delineate the tumor region.…”

“…Kim and co-workers reported MRI-guided PET/EPRI scanner to probe oxygen concentration in hypoxic regions of mice bearing squamous cell carcinoma [ 288 ]. T 2 -weighted MRI was used as an anatomical reference to delineate the tumor region.…”

“…Furthermore, the pO 2 image from EPRI shows hypoxic regions (pO 2 ≤ 10 Torr) by dark blue color in the image. Although there are some discrepancies observed between PET and EPRI images, some hypoxic regions are overlapped in both PET images using 9 and EPRI oxygen images ( Figure 18 ) [ 288 ].…”

Biological validation of electron paramagnetic resonance (EPR) image oxygen thresholds in tissue

“…Early in vitro cell work showed a sigmoidal relationship between FMISO uptake and oxygen concentration, where uptake increased at low oxygen (Rasey & Evans, 1991). The point of inflection on this sigmoidal curve would indicate the threshold of hypoxia in terms of FMISO uptake and P O 2 levels, which is currently under investigation at the Halpern laboratory in collaboration with the Kao laboratory in a home-built hybrid PET-EPR imaging system (Kim et al 2019).…”