Pulmonary elimination rate of inhaled ^99mTc‐sestamibi radioaerosol is delayed in healthy cigarette smokers

WHAT IS ALREADY KNOWN ABOUT THIS SUBJECT

• Very little is known about the physiology of P‐glycoprotein (P‐gp) expression in the lungs.

• Ex vivo evidence based on resected lung tissue suggests that pulmonary P‐gp is upregulated by cigarette smoke, but there are no in vivo studies to date.

WHAT THIS STUDY ADDS

• The novel observation that healthy cigarette smokers have a delayed pulmonary elimination rate of inhaled ^99mTc‐sestamibi, a P‐gp substrate, provides for the first time a potential method for quantifying functional pulmonary P‐gp expression that may inform about drug therapy by inhalation as well as provide a non‐invasive, quantitative, human biomarker for assessing P‐gp modulators.

AIM To explore inhaled technetium‐99m‐labelled hexakis‐methoxy‐isobutyl isonitrile (^99mTc‐sestamibi) for quantifying pulmonary P‐glycoprotein (P‐gp) expression.

METHODS The elimination rate from the lungs of ^99mTc‐sestamibi was recorded scintigraphically for 30 min following inhalation as an aerosol in healthy smokers, nonsmokers and patients with lung disease.

RESULTS^99mTc‐sestamibi elimination rates [% min⁻¹ (SD; P vs. healthy nonsmokers)] were: healthy nonsmokers, 0.43 (0.083); healthy smokers, 0.19 (0.056; P < 0.001); chronic obstructive pulmonary disease patients, 0.26 (0.077; P < 0.001). Elimination rates in three patients with interstitial lung disease were not accelerated.

CONCLUSION Cigarette smoke upregulates lung P‐gp. ^99mTc‐sestamibi elimination in normal smokers could be used to test new P‐gp modulators. The findings also have implications for inhaled drug delivery.

DOI: 10.1111/j.1365-2125.2008.03099.x

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