Lung clearance of inhaled aerosol of Tc-99m-methoxyisobutyl isonitrile: relationships with cigarette smoking, age and gender.

Tc-99m-methoxyisobutyl isonitrile (Tc-99m-MIBI) is a radiolabelled xenobiotic, the disappearance rate of which from lungs following inhalation as a radioaerosol correlates inversely with bronchopulmonary multidrug resistance protein 1 (MRP1) expression. Tc-99m-MIBI clearance has previously been shown to be delayed in cigarette smokers. The aim of the current study was to determine whether smoking correlates with bronchopulmonary MRP1 expression, to confirm that Tc-99m-MIBI disappearance rate from the lungs following inhalation is delayed in smokers, and to determine the effects of gender and age on disappearance rate. Participants underwent dynamic imaging for 40 min over the lungs following inhalation of Tc-99m-MIBI using a double-headed gamma camera. The half-time of clearance was obtained from geometric mean of anterior and posterior counts and averaged between the two lungs. Paraffin-embedded tissue obtained from healthy lung during surgery in 13 patients was graded immunohistochemically for MRP1 as negative (0), weak (1), moderate (2) or strong (3). In 4 non-smokers, grading was 1 in three and 0 in one. In 9 smokers, in contrast, expression was graded 2-3 in 8 and 1 in one (P<0·02). Mean clearance half-time in smokers (142 ± 29 min; n = 17) was longer than in non-smokers (91 ± 14 min; n = 18; P<0·0001). In non-smokers, half-times were not significantly different between men (96 ± 16; n = 6) min and women (88 ± 12 min; P = 0·2). Combining genders into one group, half-time correlated with participant age (P = 0·0005). We conclude that smoking upregulates MRP1 and delays clearance of inhaled Tc-99m-MIBI. There is no significant gender difference in non-smokers but ageing is associated with longer clearance half-times.