Effect of pattern of aerosol inhalation on clearance of technetium-99m- labeled diethylenetriamine pentaacetic acid from the lungs of normal humans

The clearance rate of inhaled aerosols of technetium-99m-labeled diethylenetriamine pentaacetic acid (^99mTc-DTPA) from the lungs provides a rapid, clinically useful, noninvasive index of pulmonary epithelial permeability. In order to identify a method that minimizes intrasubject and intersubject variability and thereby provides a reliable means to identify patients with abnormal values, we administered a submicronic aerosol of ^99mTc-DTPA to 10 healthy, nonsmoking male subjects with either tidal breathing (V̇(tidal)) or multiple vital capacity maneuvers (V(VC)). Subjects then spontaneously breathed room air while counting continued for 30 min. Monoexponential clearance rates over 7, 15, and 30 min were compared with a two-compartment, biexponential analysis over 30 min. Intrasubject reproducibility was evaluated by repeating clearance 2 to 156 days later. Monoexponential clearance following V(VC) at 30 min equaled 1.36 ± 0.55%/min compared with 0.83 ± 0.25%/min for V̇(tidal) (p < 0.025). V(VC) inhalations resulted in a larger fast compartment of 16 ± 12% compared with 3 ± 2% with tidal breathing (p < 0.01). The least intrasubject variability with coefficient of variation (CV) of ± 18% was obtained with monoexponential analyses after V̇(tidal) during 15 min of scanning and with either breathing maneuver over 30 min. Monoexponential clearance for 30 min with V̇(tidal) gave the least scatter between subjects, with CV of ± 30%. These data show that simple tidal inhalations of ^99mTc-DTPA followed by a monoexponential analysis of the 30-min time-activity curve from both lungs minimize the degree of variability between and among subjects and provide a predicted normal value of clearance of 0.83 ± 0.25%/min. The development of a more rapid curvilinear clearance followed by delivery V(VC) suggests that several deep breaths transiently increase epithelial permeability or reduce the volume of liquid in the alveolar subphase in some regions. Resting for 20 min prior to inhaling the aerosol of ^99mTc-DTPA is recommended to avoid alterations in clearance rates from deep breathing.