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

Cheow, HK; Ruparelia, P; Shankar, S; Szczepura, K; Ballinger, JR; Hartman, NG; Chilvers, ER; Peters, AM

Abstract

Objective - The clearance rate of inhaled 99mTc-sestamibi
from the lungs of healthy nonsmoking individuals is much slower than would be expected from its physical properties. The clearance rate is even slower in healthy cigarette smokers. As 99mTc-sestamibi is a substrate for P-glycoprotein (P-gp), pulmonary P-gp may be influential
in 99mTc-sestamibi clearance and may be upregulated in
smokers. 99mTc-tetrofosmin is also a substrate for P-gp,
therefore we hypothesized that it would display similar
kinetics to 99mTc-sestamibi and support a role for P-gp. We also hypothesized that administration of P-gp modulators would accelerate clearance of 99m Tc-sestamibi.
Methods - We measured clearance rates of 99m Tc-tetrofosmin in four healthy smokers and four healthy nonsmokers and of 99mTc-sestamibi in six otherwise healthy patients with psoriasis before and after 2 weeks of therapy with cyclosporine A (2.5–5 mg/kg/day) and two healthy women taking the oral contraceptive pill, as both cyclosporine and steroids are known to be P-gp modulators.
Results - The clearance rate of 99m Tc-tetrofosmin in
nonsmokers ranged from 0.38 to 0.63%/min, similar to the
previously recorded rate for 99mTc-sestamibi [0.43 (SD
0.083)%/min], but it was not delayed in smokers (range
0.42–0.97%/min). Cyclosporine had no significant effect on
99mTc-sestamibi clearance, although clearance rates in the
two women taking the oral contraceptive pill were both
fast (0.58 and 0.62%/min).
Conclusion - Although the role of P-gp expression in the
clearance of 99m Tc-sestamibi remains unproven, we conclude that 99mTc-tetrofosmin is not as P-gp-avid as 99m Tc-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.

• Journal Article Type: Article
• Publication Date: Aug 1, 2009
• Deposit Date: May 16, 2011
• Journal: Nuclear Medicine Communications
• Print ISSN: 0143-3636
• Electronic ISSN: 1473-5628
• Publisher: Lippincott, Williams & Wilkins
• Peer Reviewed: Peer Reviewed
• Volume: 30
• Issue: 8
• Pages: 617-621
• DOI: https://doi.org/10.1097/MNM.0b013e32832b9a2d
• Publisher URL: http://dx.doi.org/10.1097/MNM.0b013e32832b9a2d