3148 - Localized Oxygen Delivery via High-Pressure-Synthesized Oxygen Gas-Entrapping Materials Enhances Radiotherapy Efficacy and Improves Outcomes in Solid Tumors
Presenter(s)
U. A. Uzomah1, J. Bi2, E. Witt2, and J. D. Byrne2; 1Department of Radiation Oncology, University of Iowa Health Care, Iowa City, IA, 2University of Iowa, Iowa City, IA
Purpose/Objective(s): Tumor hypoxia significantly limits cancer treatment efficacy, promoting resistance to radiation therapy and chemotherapy. Radiation therapy requires oxygen to generate DNA-damaging free radicals. Overcoming hypoxia is crucial for improving treatment outcomes, particularly in highly hypoxic tumors. Conventional oxygenation strategies—such as hyperbaric oxygen or carbogen—suffer from transient effects, suboptimal delivery, and systemic toxicity. This study evaluates the therapeutic potential of Gas-Entrapping Materials (GeMs) for localized and sustained oxygen release, aiming to enhance tumor oxygenation, improve radiation and chemotherapy efficacy, and ultimately optimize solid tumor treatment.
Materials/Methods: To evaluate Oxygen Gas-Entrapping Materials (O2-GeMs) as an adjunct to radiation, efficacy studies were conducted in a syngeneic MPNST mouse model (n=7/arm). Foam O2-GeMs were selected for their efficient oxygen release and ease of injection. MPNST cells were isolated from harvested tumors, enzymatically dissociated, filtered, and cultured. Intramuscular tumors were established by injecting 1.25 × 105 cells into the gastrocnemius, while subcutaneous MPNST tumors were generated via flank injections of 3 × 105 cells. Intratumoral oxygen diffusion was measured using an Oxylite pO2 and temperature monitor (Oxford Optronix, UK), with the sensor inserted into the tumor via an 18-gauge angiocath. C57BL6/J mice under isoflurane anesthesia received 50 µL of 99.5% O2 foam pressurized at 200 PSI via intratumoral injection 30 min, 1 h, 6 h, and 24 h before measurements. To enhance local oxygenation, at a median tumor size of ~200 mm³, 50 µL of O2-GeMs were injected intratumorally before irradiation. Mice in a second cohort were treated with hyperbaric oxygen therapy (HBOT) at 3 ATM (the equivalent of a dive to 66 feet), with 3 cycles of 100% O2 for 30 min, followed by a 5-min break at room air prior to radiation. Mice in a third cohort were administered tirapazamine (0.12 mmol/kg/day) 30 minutes prior to irradiation. Controls were radiation alone, O2-GeMs, HBOT, tirapazamine, and no treatment. Tumor growth was monitored biweekly, with terminal volumes set at 1500 mm³ (MPNST). Using a Small Animal Radiation Research Platform (SARRP), MPNST-bearing mice received 15 Gy (1 fraction)—equivalent to preoperative sarcoma treatment in humans.
Results: Intratumorally injected foam O2-GeM led to elevated tumoral oxygen partial pressures for greater than 1 day. When combined with radiation (15 Gy), foam O2-GeM significantly inhibited tumor growth, extending survival from 13 days (control) to 25 days. ?-H2AX staining showed greater DNA damage in O2-GeM + radiation-treated tumors.
Conclusion: These findings highlight O2-GeMs as a promising strategy to overcome tumor hypoxia, enhance radiotherapy efficacy, and improve survival outcomes in solid tumors.