Daniel P. Schuster, M.D.

DEPARTMENT OF Internal Medicine
Keywords: PET, imaging, pulmonary, inflammation, gene therapy, acute lung injury

This laboratory is principally involved in using the quantitative nuclear medicine imaging technique of positron mission tomography (PET) to study pulmonary vascular disease and function. Major projects are as follows:

The acute respiratory distress syndrome (ARDS) resulting from acute lung injury (ALI) is a devastating illness of respiratory failure. Despite decades of focused research, its pathogenesis remains incompletely defined. Neutrophilic inflammation is nearly universal during early ALI/ARDS and the neutrophil is thought to be an important cellular mediator of ALI. Even so, the extent to which the neutrophil contributes to ALI remains controversial. Our hypothesis is that differences in the onset, magnitude and/or duration (i.e., the kinetics) of neutrophil activation determine the extent to which neutrophils contribute to lung tissue injury. Glycolysis is the major energy source for key neutrophil functions.Thus, increased glucose uptake by the neutrophil in support of glycolysis is a marker of neutrophil activation. Based on this property, we have shown that the pulmonary uptake of the glucose analog [¹⁸F]-fluoro-2-deoxyglucose (FDG) with positron emission tomography (PET) accurately quantifies lung neutrophil activation in animal and human models of lung injury and infection, providing a basis for using FDG-PET imaging to measure glucose uptake as a noninvasive surrogate marker of neutrophil activation. These and other imaging methods are being used to monitor neutrophil trafficking into the tissue (appearance of increased imaging signal), magnitude of neutrophil activation (intensity of the signal) and activation kinetics (duration and disappearance of the signal). Such information should provide new insights concerning the etiologic role of neutrophils in lung inflammatory disease. Eventually, such information might be useful as an indicator of disease severity, acuity or response to anti-inflammatory treatment. These studies are conducted in mice, dogs and humans.

Another recent development focuses on using PET to monitor transgene expression in lung tissue. The development of new radiopharmaceuticals and improved scanners now makes it technically possible to perform gene expression imaging in small animals, such as mice and rats. We are using these new tools to develop methods for gene expression imaging, specifically in the lung. Studies are being conducted to quantify expression after gene transfer by viral vector administration from either the airway or pulmonary vascular routes, or in transgenic murine models. Eventually, the results of these studies should provide necessary preliminary information for similar studies in humans.