In this study, poly(ethylene glycol) diacrylate (PEGDA) was surface grafted, through UV-initiated grafting, on to a microporous polypropylene (PP) membrane in order to develop and control a moisture-sensitive porous structure. Based on the concentration of the PEGDA grafting solution, as well as other variables, the pores of the membrane were filled to varying degrees with cross-linked PEGDA hydrogel, decreasing the pore sizes. This decrease in pore size was highly dependent on the grafting degree, or weight add-on of the grafted polymer. The grafting degree can be controlled by altering various grafting conditions. The surface grafted PEGDA is expected to swell significantly when exposed to moisture, through change in relative humidity or a liquid-borne pathogen, causing the pore sizes to decrease even further.This provides a microporous polypropylene membrane with improved hydrophilicity and moisture-responsive pores. The membranes will have varying levels of breathability based on the amount of moisture exposure. This will allow for a functional membrane that limits the transport of liquid-borne pathogens while providing transport of moisture vapor away from the body.iii BIOGRAPHICAL SKETCH Mark Chan was born in sunny California during the Chinese year of the Dragon, 1988. After a long and successful career from pre-school through high school,

Introduction: Convection enhanced delivery (CED) has been recently explored as an advantageous therapeutic strategy for central nervous system (CNS) tumors. One current limitation is the inability to quantitatively monitor distribution of chemotherapeutic agents. The use of surrogate tracers probably underestimates differences in distribution and clearance owing to discordant features between contrast molecules and therapeutic agents, including bioactivity, degradation, conductivity, and diffusivity. Ideally, direct labelling of a therapeutic compound would eliminate these concerns and afford a noninvasive method to monitor critical pharmacokinetic information. This ability would pave the way for designing infusion parameters and drug schedules that are expected to be unique for CED-based therapy. Methods: The small molecule kinase inhibitor dasatinib was modified with a dual-probe technology that utilizes a boronate trap to conjugate 18[F] with a near-infrared fluorophore into a single molecule, 1, allowing for visualization by positron emission tomography (PET) and near-infrared fluorescence (NIRF). The novel boronate trap allows for direct conjugation of 18[F] with minimal disruption of dasatinib's mechanism of action, resulting in a small, versatile probe with potential for other clinically relevant targets. Results: The modified drug was first tested in vitro in a PDGF-B driven p53 deficient DIPG tumor line from Nestin tv-a; p53 floxed mouse. 1 was shown to enter cells on fluorescence microscopy and inhibit cell proliferation. Antagonist drug potency of 1 as evaluated on pontine glioma in ATP-dependent luminescent cell viability, cell-permeant calcein AM, and an MTS cell proliferation assays show that the IC50, of 1 is ∼10nM. In addition, infusions of 1 were performed via CED and intravenous systemic delivery in a RCAS/tv-a PDGF-B driven with p53 deficiency Ntv-a mouse model of high-grade glioma. Compared to systemic delivery, CED was shown to be roughly 230 times more effective in delivery of the infusion to the tumor site. Maximal glioma delivery occurred at 115 min post a 20 min infusion, with clearance occurring with a half-life of 45 min after maximum delivery. Conclusion: Dasatinib was modified to give 1, an agent that can be imaged non-invasively by fluorescence and positron emission tomography (PET). The modified dasatinib showed little modification in biologic activity when compared to unmodified dasatinib and exhibited cytotoxic effects in vitro in glioma cell culture. CED shows a clear benefit to intravenous delivery when the target site is in the CNS. The dual-label probe technology's versatility and minimal biologic profile lends itself to various clinical uses, including the study of different therapeutic agents and delivery routes without the need to rely on surrogate tracers. Citation Format: Melinda Wang, Zhiping Zhou, Hari Krishna Kommidi, Melanie Schweitzer, Mark Chan, Yue Linda Wu, Ranjodh Singh, Richard Ting, Mark M. Souweidane. Intra-cerebral pharmacokinetic monitoring of a tyrosine kinase inhibitor (theranostic 18[F]-PET/NIRF labeled dasatinib) delivered via convection-enhanced delivery. [abstract]. In: Proceedings of the 107th Annual Meeting of the American Association for Cancer Research; 2016 Apr 16-20; New Orleans, LA. Philadelphia (PA): AACR; Cancer Res 2016;76(14 Suppl):Abstract nr 1367.