Does P-glycoprotein have a role in the lung clearances of inhaled 99mTc-sestamibi and 99mTc-tetrofosmin?

Abstract

Although the role of P-gp expression in the clearance of 99mTc-sestamibi remains unproven, we conclude that 99mTc-tetrofosmin is not as P-gp-avid as 99mTc-sestamibi. A role for P-gp expression in the clearance of 99mTc-sestamibi remains unproven. Higher doses of P-gp inhibitors will be required and clearance rates correlated with immunohistochemical expression of P-gp.

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

“…In line with murine studies (Okamura et al ., ), P‐gp appears to play no significant role in protection of the organism from xenobiotics entering via the airways. Surprisingly, the clearance rate of Tc‐99m‐tetrofosmin, which along with Tc‐99m‐MIBI is used primarily in routine clinical practice to image myocardial perfusion, was not delayed in smokers versus non‐smokers (Cheow et al ., ), suggesting that Tc‐99m‐tetrofosmin has more affinity for P‐gp than MRP1. Also, surprisingly, inhaled Tc‐99m‐MIBI in rabbits had a faster clearance half‐time than Tc‐99m‐DTPA (Nilsson & Wollmer, ).…”

“…() speculated that this was the result of smoke‐induced upregulation of bronchopulmonary P‐glycoprotein (P‐gp), preventing the tracer from entering bronchopulmonary cells and subsequently undergoing transport across the lung blood‐gas barrier into the pulmonary circulation. Surprisingly, however, in a later study, they found that the lung clearance rate of the closely related tracer, Tc‐99m‐tetrofosmin, which like Tc‐99m‐MIBI is used in routine clinical practice to image myocardial perfusion and tumours, was not delayed in healthy smokers (Cheow et al ., ).…”

Does the Clearance of Inhaled99mTc-Sestamibi Correlate with Multidrug Resistance Protein 1 Expression in the Human Lung?

“…Apart from a single animal study by Okamura et al (32), who demonstrated MRP1 as the prime drug transporter across the lung epithelium with P-gp playing no significant role, there is a lack of functional was due to the active efflux of inhaled 99m Tc-sestamibi mediated by increased P-gp expression in the alveolar epithelium, pumping it back into the airspaces (25). Interestingly, this group showed no difference between smokers and nonsmokers with respect to the lung clearance rate of inhaled 99m Tctetrofosmin (26). There was, however, no immunohistochemical correlation available to confirm the postulation.…”

“…They observed that it was significantly slower than the clearance of the hydrophilic radioaerosol, Tcpentetate (25), and hypothesized that the delayed clearance of 99m Tc-sestamibi was due to expression of P-gp in the airway epithelium (26). The clearance rate of inhaled 99m Tc-sestamibi from the lungs was further significantly delayed in healthy smokers versus nonsmokers, and it was hypothesized that this was the result of smoke-induced up-regulation of P-gp (25).…”

“…20%) in inhaled 99m Tc-sestamibi clearance rates between smokers and nonsmokers, while no significant difference was seen between healthy volunteers compared with COPD patients. They postulated that the delayed clearance of 99m Tc-sestamibi across the alveolocapillary barrier was regulated by active binding and efflux of Tcsestamibi by P-gp expressed in the lung tissue (26). They also postulated that delayed 99m Tc-sestamibi clearance in smokers compared with nonsmokers and protection against air pollution and inhaled toxic substances, such as those present in cigarette smoke (31).…”