An optical therapeutic protocol to treat brain metastasis by mapping NIR activated drug release: A pilot study

Treatment of Central Nervous System (CNS) metastasis poses a critical clinical challenge due to limitations in drug uptake across the blood brain barrier and blood-cerebrospinal fluid barrier. Recent research has shown the efficacy of using macrophages as drug carriers to target metastatic sites in the brain, which can then be activated by illuminating with near infrared radiation. The goal of this research is to develop an optically targeted therapeutic treatment of metastasis, specifically for metastatic breast cancer of the brain. As a first step towards accomplishing this, we developed a 3D Monte Carlo photon transport code capable of simulating phantoms with optical properties of brain and tumor; and validated the Monte Carlo simulated photon fluence within brain phantoms using an optical dosimetry probe. The phantom studies showed good correlation (correlation coefficient R=0.977) between the probe measurements and the Monte Carlo simulation in a white matter phantom (reduced scattering coefficient μs1=8.25mm^-1, absorption coefficient μa=0.005 mm-1). Our future steps will be to implement the Monte Carlo to map out photon energy distribution in the brain, and subsequent drug release, by segmenting & translating head CT image volumes to corresponding optical properties of brain tissues. To access the therapeutic response, changes in the vascular physiology of the brain due to Her2 inhibition will be measured using dynamic contrast-enhanced imaging (e.g. DCE-CT), and with Monte Carlo based optical fluence maps. An optical treatment plan, using fast Monte Carlo software, optimized with CT segmented image volumes, would significantly reduce the treatment time and allow targeted drug activation while sparing healthy tissues.