Program Information
Microbeam Radiation Is More Effective and Safe Than Conventional Radiation in Enhancing Tumor Delivery of Nanoscale Anti-Cancer Drugs
S Chang*, J Rivera , L Herity , L Price , A Madden , J Roques , C Santos , D Darr , W Zamboni , UNC School of Medicine, Chapel Hill, NC
Presentations
MO-F-FS1-6 (Monday, July 31, 2017) 4:30 PM - 6:00 PM Room: Four Seasons 1
Purpose: We use radiation to overcome the critical barrier of low tumor uptake associated with carrier mediated anticancer agents (CMAs), such as liposomes and nanoparticles (NPs), without added toxicity. CMAs belong to a new class of promising anticancer drugs that can prolong duration of exposure, selectively deliver entrapped drug to the tumor, and improve therapeutic index. However, the potentials are unrealized due to the low tumor uptake. We have demonstrated previously that microbeam radiation (MRT) significantly enhanced the drug tumor delivery. In this work we compare the enhancement of tumor delivery between MRT and the conventional broadbeam radiation (BRT) and investigated the radiation dose dependence.
Methods: A genetically-engineered-mouse model of triple negative breast cancer solid tumor is used. PEGylated liposomal doxorubicin (PLD), a FDA approved CMA for solid tumors, is injected 24 hours post targeted tumor radiation. Plasma and tumor pharmacokinetic studies of PLD were performed. Mice received a single radiation treatment (mock, 28 Gy BRT, 28 Gy MRT, or 100 Gy MRT) followed 24 h later by PLD 6 mg/kg IV x1. Each mouse was sacrificed 5 min or 24 h after administration of PLD. Doxorubicin concentrations in plasma and tumor were measured by HPLC with fluorescence.
Results: All radiation groups showed enhanced total Doxorubicin concentration in tumor compared to PLD drug alone at 24 hours with the 100Gy MRT group showing the largest enhancement and the BRT 28Gy the least. The ratio of tumor to plasma drug concentration is the highest for the 100Gy MRT group (1.45±0.7), PLD alone lowest (0.2±0.04), and no statistical difference between the 28Gy MRT and 28Gy BRT groups.
Conclusion: Spatially-fractionated radiation such as microbeam radiation modulate tumor microenvironment different than conventional radiation and it has the potential to safely enhance the tumor of delivery of a new class of anticancer drugs.
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