Abstract 2784: Intratracheally delivered perflurocarbon nanoparticles to enhance radiotherapy against lung cancer

• Published in: Cancer research (Chicago, Ill.) Ill.), 2020-08, Vol.80 (16_Supplement), p.2784-2784
• Main Authors: Wu, Lina, Xie, Jin
• Format: Article
• Language: English
• ISSN: 0008-5472; 1538-7445
• DOI: 10.1158/1538-7445.AM2020-2784

Radiotherapy (RT) is a major treatment modality for lung cancer. Despite of technological advances, the five-year survival rate remains low. There is an urgent need of new and effective approaches that can selectively sensitize lung cancer cells to radiation. In this proof-of-concept study, we tested whether intratracheally(IT) delivered perfluorocarbon nanoparticles (PFC NPs) can enhance radiotherapy against lung cancer. We hypothesize that the approach can capitalize on the oxygen-loading capacity of PFC NPs and solve the unfavorable delivery problem associated with systemically injected PFC NPs. Therapy studies were performed in mice bearing subcutaneously inoculated H460 tumors and in orthotopicVX2 tumor models established on New Zealand white rabbits. PET/CT, 19F-MRI, and DCE-MRI were employed to assess PFC NPs delivery and treatment outcomes. 1H-MRS was performed on tumors from different treatment groups and the results were compared with in vivo imaging. For both tumor models, animals were divided into four groups (n=3 for rabbits and 5 for mice): (1) control; (2) PFC NPs only; (3) radiotherapy only; and (4) RT+PFC NPs group. Tumor tissues were subjected to pathology analysis and the results were compared with imaging data. Urine samples were collected and analyzed by UPLC-Q-TOF-MS/MS to assess metastasis. Our results showed that combining IT delivered PFC NPs and radiotherapy led to significantly enhanced tumor growth inhibition. Specifically, 19F-MRI confirmed that PFC NPs can deliver O2 to tumors and increase the mean pO2. DCE-MRI showed distinct tumor blood perfusion behaviors in the RT+PFC NPs group (P