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

Abstract

Summary 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.

Tobacco Smoke and Inhaled Drugs Alter Expression and Activity of Multidrug Resistance-Associated Protein-1 (MRP1) in Human Distal Lung Epithelial Cells in vitro

“…Reduced MRP1 protein levels were observed in lung tissue of COPD patients ( van der Deen et al, 2006 ) and in an experimental rat model of COPD ( Wu et al, 2019 ) using immunohistochemistry analysis. Moreover, the pulmonary clearance of inhaled [ 99 m Tc] methoxyisobutyl isonitrile ([ 99 m Tc] sestamibi), a radiolabeled MRP1 substrate, has been recorded to decrease in smokers and the decrement was attributed to modulation in MRP1 activity and expression profile ( Mohan et al, 2019 ). The distal lung epithelium has been reported to be the initial site of development of tobacco smoke-induced diseases such as COPD ( Baskoro et al, 2018 ).…”

Aerosolised micro and nanoparticle: formulation and delivery method for lung imaging

“…This simple method can also be used to aerosolise radioactive material since a commercial nebuliser equipped with the lead container, e.g. SmartVent™, is available for this purpose [95]. Furthermore, different types of nebulisers lead to dissimilar performance, providing device options to adapt to various drug cargo types [96].…”

Red cell volume measurement: using technetium as a replacement for chromium

“…Caveats to the above speculation are that in nonsmokers, we found first, no difference in clearance rate between men and women, and second, a trend for clearance to be delayed, rather than accelerated, in older subjects [ 9 ]. However, as implied in the WHO scientific brief alluded to above, the known poorer clinical outcome in the elderly and in males is a separate statistic from infection rate itself.…”