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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 and Peters, AM 2009, 'Does P-glycoprotein have a role in the lung clearances of inhaled 99m Tc-sestamibi and 99m Tc-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 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.

    Item Type: Article
    Themes: Health and Wellbeing
    Schools: Colleges and Schools > College of Health & Social Care
    Colleges and Schools > College of Health & Social Care > School of Health Sciences
    Journal or Publication Title: Nuclear Medicine Communications
    Publisher: Chapman & Hall
    Refereed: Yes
    ISSN: 0143-3636
    Depositing User: RH Shuttleworth
    Date Deposited: 16 May 2011 10:49
    Last Modified: 20 Aug 2013 17:52
    URI: http://usir.salford.ac.uk/id/eprint/15788

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