This subproject is one of many research subprojects utilizing the resources provided by a Center grant funded by NIH/NCRR. The subproject and investigator (PI) may have received primary funding from another NIH source, and thus could be represented in other CRISP entries. The institution listed is for the Center, which is not necessarily the institution for the investigator. The overall goal of this work is to determine if deuterated water can be used as a suitable in vivo surrogate marker for the distribution of drugs delivered into the intracerebral compartment by convection- enhanced delivery. Specific goals of this project are to develop a coil suitable for measuring deuterated water in in vitro systems, small and large animals systems, and ultimately in humans. Our laboratory has pioneered work on convection-enhanced delivery of therapeutic molecules into the brain in patients with malignant gliomas. Convection-enhanced delivery is a novel technique that percolates drug throught brain parenchyma via a small catheter using a pressure head that exceeds interstitual pressures without causing tissue disruption. We previously studied distribution of these molecules using 123I-labeled albumin injected by us into animals and humans with brain tumors. This demonstrated that convection-enhanced delivery is a promising technique for delivering drugs at homogenous concentrations for broad distances throughout the brain. We learned, however, that the parameters of drug distribution are important to ensure adequate coverage of areas at risk for tumor recurrence. Because I123I-labeled albumin is expensive, and the resolution of SPECT scanning is poor, newer tracers are needed to further optimize these studies and validate our computer algorhythm for catheter placement and distribution prediction. By using deuterated water, we hope to accomplish a high-resolution method of tracking the distribution of these agents in the human brain. We would be able to develop these studies based on our existing IND and clinical protocol for infusing I123-labeled albumin. Furthermore, deuterated water would be a more convenient and broadly applicable substance for combining with the various drugs that may ultimately be applied in this clinical scenario.
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