HK Cheow
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; Ballinger, JR; Hartman, NG; Chilvers, ER; Michael Peters, A
Authors
P Ruparelia
S Shankar
Ms Katy Szczepura K.Szczepura@salford.ac.uk
Reader
JR Ballinger
NG Hartman
ER Chilvers
A Michael Peters
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.
Citation
Cheow, H., Ruparelia, P., Shankar, S., Szczepura, K., Ballinger, J., Hartman, N., …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), 617-621. https://doi.org/10.1097/mnm.0b013e32832b9a2d
Journal Article Type | Article |
---|---|
Acceptance Date | Mar 13, 2009 |
Publication Date | Aug 1, 2009 |
Deposit Date | Feb 26, 2021 |
Journal | Nuclear Medicine Communications |
Print ISSN | 0143-3636 |
Electronic ISSN | 1473-5628 |
Publisher | Lippincott, Williams & Wilkins |
Volume | 30 |
Issue | 8 |
Pages | 617-621 |
DOI | https://doi.org/10.1097/mnm.0b013e32832b9a2d |
Publisher URL | https://doi.org/10.1097/MNM.0b013e32832b9a2d |
Related Public URLs | http://www.nuclearmedicinecomm.com/ |
Additional Information | Funders : AstraZeneca;Cambridge NIHR Biomedical Research Centre |
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