Abstract
About 30% of breast cancers metastasize to the brain; those widely disseminated are fatal typically in 3–4 months, even with the best available treatments, including 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, with uptake peaks at 4.5%. This is calculated to provide a dose enhancement factor of approximately 5.5 (peaks at 8.0), the highest ever reported for any radiation-enhancing agents. With RT alone (15 Gy, single dose), 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.
Highlights
About 30% of breast cancers metastasize to the brain; those widely disseminated are fatal typically in 3–4 months, even with the best available treatments, including surgery, drugs, and radiotherapy
Primary brain tumors include the most aggressive glioblastoma multiform (GBM) which after optimal therapy nearly always recurs after which most patients do not survive beyond one year[3,4]
More prevalent are brain tumors from other parts of the body that metastasize to the brain and account for about 90% of all brain tumors
Summary
About 30% of breast cancers metastasize to the brain; those widely disseminated are fatal typically in 3–4 months, even with the best available treatments, including surgery, drugs, and radiotherapy To address this dire situation, we have developed iodine nanoparticles (INPs) that target brain tumors after intravenous (IV) injection. We constructed iodine nanoparticles that are very well tolerated with no demonstrable toxicity, have a pathway for biodegradation, a long blood half-life (40 h), an appropriate size for tumor uptake (20 nm), and are lower in c ost[25] These were used previously to treat athymic nude mice with an advanced intracerebral human glioma resulting in two to threefold median life extensions[7]. In the study presented here, using a human triple-negative breast tumor growing in the athymic mouse brain, median survival with INP-RT increased by about two-fold, but significantly, 40% of the mice experienced from 7 to > 20-fold longer life extensions compared to RT only
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