In vivo measurements of pulmonary angiotensin-converting enzyme kinetics. II. Implementation and application

We measured pulmonary angiotensin-converting enzyme (ACE) kinetics with fluorine-18 captopril and positron emission tomographic (PET) imaging in five control dogs and in five dogs after 20-30 min of left caudal lobe (LCL) hypoxic ventilation. Time-activity data obtained with PET were interpreted with a compartmental receptor model relating changes in tissue and blood activity to one another within the region. In control dogs, the mean ratio of regional blood flow (measured by PET) between left and right dorsal lung regions was 0.90 +/- 0.16 (SD) vs. 0.54 +/- 0.24 (P < 0.05) in LCL hypoxic dogs. In control dogs, the amount of perfused unbound enzyme normalized to regional extravascular water concentration (Bmax/EVLW) averaged 13.3 +/- 8.9 x 10(-6) mmol ACE/ml EVLW; the ratio of regional values between the left and right sides was 1.02 +/- 0.18. In the LCL hypoxic dogs, Bmax/EVLW was 9.7 +/- 11.3 x 10(-6) mmol/ml hypoxic lung region and the ratio was 0.47 +/- 0.31 (P < 0.05). In control dogs, the coefficient of variation for Bmax/EVLW among regions was only 19 +/- 10%, although the between-dog variation was greater (64 +/- 4%). We conclude that this completely noninvasive method appears to be a promising approach for evaluating the expression of pulmonary ACE in vivo.