Pet and Mri-Guided Focused Ultrasound Surgery for Hypoxic-Tissue Ablation Combined With Radiotherapy in Solid Tumors

Background : The raonale was to develop an ablaon approach to destroy regions of tumor resistant to radiaon and thus reduce theme required for whole tumor ablaon, while improving overall tumor control aer radiotherapy. Materials and Methods : The system is composed of a micro positron emission tomography (mPET), 7T magnec resonance imaging (MRI), and a customized MRI-compable focused ultrasound applicator. 18F- fluoromisonidazole (18F-miso) radioacve tracer delineated hypoxic regions based on a threshold tumor/muscle acvity rao. 18F -miso PET/MRI fused images were used for targeng tumor hypoxic regions for focused ultrasound ablaon. With MRI real-�me temperature imaging guid ance, PET-detected hypoxic regions of tumor could be selecvely ablated to temperatures (T>55 o C). In vivo validaon experiments were performed in SCK and 4T1 murine mammary carcinomas. In two tumor response assays, sequence dependence of combined radiotherapy and ablaon was studied in the SCK tumor model. Tumor ablaon was performed using a conducve probe or focused ultrasound and ionizing radiaon administered in single doses of 15-20 Gy. Results : Tumor growth was abolished when ablaon was applied immediately AFTER radiaon while interesngly; when ablaon was administered immediately BEFORE radiaon, there was no difference in observed growth delay compared to ablaon or radiaon alone. Conclusion : PET and MRI guided focused ultrasound surgery (MRgFUS) of tumor hypoxic regions is feasible and will be potenally useful for preclinical studies using ultrasound, radiaon or chemotherapy. This study suggests that radiaon precedes ablave therapy to avoid unwanted stress response or addional hypoxia induced by the ablaon, potenally confounding the improved response potenal for combined therapy.