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

Cheow, HK, Ruparelia, P, Shankar, S, Szczepura, K ORCID: https://orcid.org/0000-0002-2566-3308, Ballinger, JR, Hartman, NG, Chilvers, ER and Michael Peters, A 2009, 'Does P-glycoprotein have a role in the lung clearances of inhaled 99mTc-sestamibi and 99mTc-tetrofosmin?' , Nuclear Medicine Communications, 30 (8) , pp. 617-621.

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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 99mTc-sestamibi. Methods We measured clearance rates of 99mTc-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 99mTc-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 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.

Item Type: Article
Schools: Schools > School of Health and Society
Journal or Publication Title: Nuclear Medicine Communications
Publisher: Lippincott, Williams & Wilkins
ISSN: 0143-3636
Related URLs:
Funders: AstraZeneca, Cambridge NIHR Biomedical Research Centre
Depositing User: K Szczepura
Date Deposited: 26 Feb 2021 13:26
Last Modified: 27 Aug 2021 21:50
URI: http://usir.salford.ac.uk/id/eprint/59685

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