Measurement of the clearance rate of inhaled aerosols of Tc-99m-diethy
lenetriamine pentaacetic acid (DTPA) from distal airway to pulmonary c
apillary is a sensitive technique for the detection of lung injury. As
the solute diffuses across the blood-gas barrier, the concentration i
n circulating blood increases, giving rise to a background signal supe
rimposed on the signal from residual DTPA in the airway. Background su
btraction is conventionally based on the thigh, but this tissue has th
e disadvantage in that its composition, in terms of the relative volum
es of its extracellular extravascular and intravascular compartments (
a ratio of similar to 4:1), is quite different from that of the lung (
<1:6). With comparison to the thigh, we examined alternative regions f
or background, liver, and cranium, which have extravascular-to-intrava
scular compartment ratios much closer to these for the lung, to determ
ine the most appropriate background for correction of the pulmonary si
gnal. From 1 min after intravenous injection of Tc-99m-DTPA, the time-
activity curves recorded by a gamma camera over the liver and lung in
a group of otherwise normal cigarette smokers decreased up to 30 min a
fter injection, with time courses that could essentially be superimpos
ed on each other; the curve recorded over the thigh with a separate sc
intillation probe continued to increase. The curve recorded over the c
ranium had a time course similar to that for the liver and lung. Follo
wing aerosol inhalation, the lung clearance rates over the initial 7 m
in when background subtraction was used, based on the liver, cranium,
and thigh were, respectively, 4.9 +/- 2.9, 4.7 +/- 2.6, and 5.4 +/- 3.
4 (SD) %/min, compared with 4.1 +/- 2.2%/min without subtraction. The
corresponding values based on 30 min of data were 3.3 +/- 1.4, 3.4 +/-
1.4, 4.2 +/- 2.3, and 2.8 +/- 1.0%/min. When the liver was used for b
ackground, the lung clearance curves were clearly multiexponential, wh
ereas thigh correction tended to give curves that were monoexponential
or even convex upward on semilogarithmic axes. With an appropriate re
gion for background, the true shape of a lung curve can be identified,
which permits the study of an intervention on the clearance while it
is in progress. The intravenous DTPA, required for calibrating the bac
kground regions, can be given before inhalation of the tracer.