A spectral CT study on iodine augmentation of radiation therapy and its potential for combination with chemotherapy

High-Z based nanoparticles (NP) are emerging as promising agents for both cancer radiotherapy (RT) and CT imaging. NPs can be delivered to tumors via the enhanced permeability and retention (EPR) effect and they preferentially accumulate in tumor's perivascular region. Both gold and iodine NPs produce low-energy, short-range photoelectrons during RT, boosting radiation dose. Using spectral CT imaging, we sought to investigate (1) if iodine nanoparticles augmentation of RT increases vascular permeability in solid tumors, and (2) if iodine-RT induced changes in tumor vascular permeability improves delivery of nanoparticle-based chemotherapeutics. In vivo studies were performed in a carcinogen-induced and genetically engineered primary mouse model of soft tissue sarcoma. Tumor-bearing mice in test group were intravenously injected with liposomal-iodine (Lip-I) (1.32 g I/kg) on day 0. On day 1, both test (with Lip-I) and control (without Lip-I) mice received RT (single dose, 10 Gy). One day post-RT (day 2), all mice were intravenously injected with liposomal gadolinium (Lip-Gd) (0.32 g Gd/kg), a surrogate of nanoparticle chemotherapeutic agent. Three days later (day 5) mice were imaged on our hybrid spectral micro-CT system. A dual source pre-clinical CT prototype system that combines a photon counting detector (PCD) and an energy integrating detector (EID) in a single hybrid system served as our imaging device. The results demonstrate that Lip-I augmented RT, resulting in increased tumor vascular permeability compared to control mice treated with RT alone. Consequently, Lip-I +RT treated mice demonstrated a 4- fold higher intra-tumoral accumulation of Lip-Gd compared to RT alone treated mice. In conclusion, our work suggests that Lip-I augments RT-induced effects on tumor vasculature, resulting in increased vascular permeability and higher intratumoral deposition of chemotherapeutic nanoparticles.