[18F]-FDG CT and PET Scans in a Monocrotaline Rat Model to Understand the Role of the Brain in Pulmonary Arterial Hypertension Development

Introduction/Problem statement: Pulmonary arterial hypertension (PAH), classified as Group 1 pulmonary hypertension is a rare, progressive disease with a 50% survival rate. Common symptoms include dyspnea, fatigue, and lightheadedness. The fatal effects of the disease occur because of right ventricular failure exacerbated by elevated mean arterial pressure and chronic pulmonary vascular resistance. The role of the brain in PAH is not well understood, however elevated sympathetic nerve activity implicates the baro- and chemo-flex, physiological mechanisms thate modulate sympathetic tone through changes in pressure, and blood chemistry respectively. Methods/Approach: Sprague Dawley rats were separated into treatment and control groups, receiving 60mg/kg subcutaneous injections of monocrotaline (MCT) or phosphate buffer saline (PBS), respectively. Rats then underwent echocardiography to confirm the onset of PAH. Under isoflurane anesthesia, [18F]-FDG was administered intravenously, which was utilized by metabolically active cells. Using a Tri-modality scanner (Mi Labs; Netherlands), CT and PET scans were acquired so that a protocol to assess the metabolic differences between MCT and PBS control rats can be optimized so that differences in tissues such as the heart and brain can be assessed. Findings/Implications: This research aims to provide pilot data which will help to optimize CT and PET scanning using [18F]-FDG in rats with PAH compared to normotensive controls. Our findings will help inform future studies that rely on these data as end-point measurements and so enhance our understanding of PAH mechanisms, ultimately guiding future research and treatment strategies.