Abstract PS14-16: Novel iodine nanoparticle micro-localization and resultant radiotherapy-enhancement of triple negative human breast cancer growing in the brains of athymic nude mice

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Abstract About 30% of breast cancers metastasize to brain; those widely disseminated are fatal typically in 3-4 months, even with the best available surgery, drugs, and radiotherapy. To address this dire situation, we have developed iodine nanoparticles (INPs) that target brain tumors after intravenous (IV) injection. The iodine then absorbs X-rays during radiotherapy (RT), creating free radicals and local tumor damage, effectively boosting the local RT dose at the tumor. Efficacy was tested using the very aggressive human triple negative breast cancer (TNBC, MDA-MB-231 cells) growing in the brains of athymic nude mice. With a well-tolerated non-toxic IV dose of the INPs (7 g iodine/kg body weight), tumors showed a heavily iodinated rim surrounding the tumor having an average uptake of 2.9% iodine by weight (peaks at 4.5%), calculated to provide dose enhancement factors of ~5.5 (peaks at 8.0) – the highest ever reported for any radio-enhancing agents. With 15-Gy, single dose RT, all animals died by 72 days; INP pretreatment resulted in longer-term remissions with 40% of mice surviving 150 days and 30% surviving > 280 days (Hainfeld et al., 2020). Fluorescence confocal microscopy revealed most INP staining co-localized with CD31 in the tumor center and tumor periphery. Greatest INP and CD31 staining was in the tumor periphery, the region of increased Micro CT contrast. Tumor cells are seen to line irregularly-shaped spaces (ISS) with INP and CD31 staining very close to or on the tumor cell surface and with PAS stain on their boundary and may represent a unique form of CD31-expressing vascular mimicry in intracerebral 231-tumors. INP and CD31 co-staining is also seen around ISS formed around tumor cells migrating on CD31 positive blood-vessels. We hypothesize that breast cancer cells secrete a CD31 containing scaffold to which IV-injected INPs bind; tumor cells proliferate along the scaffold forming the boundaries of the ISS creating a form of vascular mimicry. The significant radiation dose enhancement to the prolific INP-binding ISS found throughout the tumor but concentrated in the tumor rim, may contribute significantly to the life extensions observed after INP-RT; vascular mimicry could represent a new nanoparticle, particularly INP, tumor-homing target. Citation Format: Sharif M Ridwan, James F Hainfeld, Yaroslav Stanishevskiy, Vanessa Ross, Henry M Smilowitz. Novel iodine nanoparticle micro-localization and resultant radiotherapy-enhancement of triple negative human breast cancer growing in the brains of athymic nude mice [abstract]. In: Proceedings of the 2020 San Antonio Breast Cancer Virtual Symposium; 2020 Dec 8-11; San Antonio, TX. Philadelphia (PA): AACR; Cancer Res 2021;81(4 Suppl):Abstract nr PS14-16.