AWARD NUMBER: W81XWH-13-1-0341 TITLE: “Delivery of Nano-Tethered Therapies to Brain Metastases of Primary Breast Cancer Using a Cellular Trojan Horse” PRINCIPAL INVESTIGATOR:

Purpose: The purpose of this study is to develop an alternate empirical approach to estimate near-infra-red (NIR) photonpropagation and quantify optically induced drug release in brain metastasis, without relying on computationallyexpensive Monte Carlo techniques (gold standard). Targeted drug delivery with optically induced drug release is a non-invasive means to treat cancers and metastasis. This study is part of a larger project to treat brain metastasis bydelivering lapatinib-drug-nanocomplexes and activating NIR-induced drug release. The empirical model was developedusing a weighted approach to estimate photon scattering in tissues and calibrated using a GPU based 3D Monte Carlo.The empirical model was developed and tested against Monte Carlo in optical brain phantoms for pencil beams (width1mm) and broad beams (width 10mm). The empirical algorithm was tested against the Monte Carlo for different albedosalong with diffusion equation and in simulated brain phantoms resembling white-matter (μs‟=8.25mm-1, μa=0.005mm-1)and gray-matter (μs‟=2.45mm-1, μa=0.035mm-1) at wavelength 800nm. The goodness of fit between the two models wasdetermined using coefficient of determination (R-squared analysis). Preliminary results show the Empirical algorithmmatches Monte Carlo simulated fluence over a wide range of albedo (0.7 to 0.99), while the diffusion equation fails forlower albedo. The photon fluence generated by empirical code matched the Monte Carlo in homogeneous phantoms(R2=0.99). While GPU based Monte Carlo achieved 300X acceleration compared to earlier CPU based models, theempirical code is 700X faster than the Monte Carlo for a typical super-Gaussian laser beam.