We propose using the quantitative non-invasive imaging technique of positron emission tomography to measure pulmonary angiotensin converting enzyme (ACE) kinetics after the iv administration of fluorine-18 (F-18) labeled captopril, a known ACE inhibitor. Since ACE is an important regulatory enzyme of the renin-angiotensin and kinin-kallikrein systems, and since it is located along the pulmonary vascular endothelium, it is well positioned as a potential marker of systemic and pulmonary vascular biology. Studies are designed to achieve the following specific aims: 1. to determine the proper scanning protocol and mathematical model to estimate ACE kinetic parameters, and to determine the saturability of the enzyme system, 2. to use information from these studies to design and test the proper experimental protocol for separately calculating the number of available enzyme receptors, Bmax, and the affinity constant, ka, for the receptor-ligand interaction, 3. to determine the kinetics of alternative ACE inhibitors, 4. to evaluate this protocol in separate studies after specific interventions designed to change intrapulmonary blood volume, regional pulmonary blood flow and to induce acute lung injury, and 5. to extend the protocol to clinical disorders involving abnormal ACE kinetics or the pulmonary vasculature. In addition to providing new information about pulmonary ACE kinetics, these studies will lay the proper foundation for extending this technique to other PET methods for evaluating other non- respiratory functions of the lung.
| Tanaka, Y; Schuster, D P; Davis, E C et al. (1996) The role of vascular injury and hemodynamics in rat pulmonary artery remodeling. J Clin Invest 98:434-42 |
| Schuster, D P; Crouch, E C; Parks, W C et al. (1996) Angiotensin converting enzyme expression in primary pulmonary hypertension. Am J Respir Crit Care Med 154:1087-91 |
| Schuster, D P; McCarthy, T J; Welch, M J et al. (1995) In vivo measurements of pulmonary angiotensin-converting enzyme kinetics. II. Implementation and application. J Appl Physiol 78:1169-78 |
| Markham, J; McCarthy, T J; Welch, M J et al. (1995) In vivo measurements of pulmonary angiotensin-converting enzyme kinetics. I. Theory and error analysis. J Appl Physiol 78:1158-68 |
