Monitoring the Radiosensitizing Effects of Implantable Micro-oxygen Generator in Pancreatic Cancer Xenografts

Purpose/Objective(s): Over the past decades, little progress has been made to improve the extremely low survival rates observed in patients diagnosed with pancreatic cancer (overall 5-year survival rate is less than 5%). Extreme hypoxia observed in pancreatic tumors significantly contributes to the ineffectiveness of conventional radiation and chemotherapy. To overcome this hypoxia-induced ineffective radiation treatment, we used a novel device, the Implantable Micro-oxygen Generator (IMOG) for in-situ tumor oxygenation as a radiation sensitizer. Due to its small size, IMOG can be directly inserted into tumor and stimulated by wireless ultrasonic power to electrolyze water inside tumor to generate oxygen. Materials/Methods: Five nude rats with BxPC-3 pancreatic tumors in both flanks were used for longitudinally measuring oxygen produced by IMOG through the Phase Measurement System. For each rat, one tumor was inserted with IMOG and the other was used as control. Thirty-nine nude mice with BxPC-3 tumor were divided into three groups: 5 Gy (tumors implanted with inactivated IMOG and received 5 Gy x-ray, n Z 14), IMOG plus 5 Gy (tumor implanted with functional IMOG and received 5 Gy x-ray, n Z 19), and 7 Gy (tumors received 7 Gy x-ray, n Z 6). Localized x-ray irradiation (320 kV Precision x-ray machine, set at 250 kV, 12.5 mA, dose rate 1.594 Gy/min) was given to the tumors immediately after 10 minutes of IMOG stimulation. Tumor size in each group was measured every three days with digital caliper. Detailed description of IMOG implantation and oxygen measurement by NeoFox system was described in the previously published paper by Maleki et al. Results: Significant oxygen production inside tumor by wireless ultrasonically-powered IMOG was observed using the NeoFox system in a longitudinal fashion. The tumor growth study demonstrated that tumors with the functional IMOG treated by 5 Gy radiation exhibited the equivalent tumor growth inhibition as the 7 Gy radiation treated tumors. Conclusion: Our study confirmed that activated IMOG is able to produce sufficient oxygen to radiosensitize pancreatic tumors, generating about 2 Gy boost effect. Author Disclosure: N. Cao: None. S. Song: None. M.R. Shaffer: None. T. Maleki: O. Patent/License Fee/Copyright; Patent. M. Cao: None. C. Kao: None. K.M. Stantz: None. B. Ziaie: E. Research Grant; Research Grant. O. Patent/License Fee/Copyright; Patent. S. Ko: E. Research Grant; Research Grant. O. Patent/License Fee/Copyright; Patent.