Back to Search
Start Over
Does P-glycoprotein have a role in the lung clearances of inhaled 99mTc-sestamibi and 99mTc-tetrofosmin?
- Source :
-
Nuclear medicine communications [Nucl Med Commun] 2009 Aug; Vol. 30 (8), pp. 617-21. - Publication Year :
- 2009
-
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.<br />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.<br />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).<br />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.
- Subjects :
- Administration, Inhalation
Administration, Oral
Adult
Cyclosporine administration & dosage
Cyclosporine pharmacology
Female
Humans
Lung drug effects
Male
Metabolic Clearance Rate drug effects
Middle Aged
Smoking
Steroids administration & dosage
Steroids pharmacology
ATP Binding Cassette Transporter, Subfamily B, Member 1 metabolism
Lung metabolism
Organophosphorus Compounds administration & dosage
Organophosphorus Compounds pharmacokinetics
Organotechnetium Compounds administration & dosage
Organotechnetium Compounds pharmacokinetics
Technetium Tc 99m Sestamibi administration & dosage
Technetium Tc 99m Sestamibi pharmacokinetics
Subjects
Details
- Language :
- English
- ISSN :
- 1473-5628
- Volume :
- 30
- Issue :
- 8
- Database :
- MEDLINE
- Journal :
- Nuclear medicine communications
- Publication Type :
- Academic Journal
- Accession number :
- 19474770
- Full Text :
- https://doi.org/10.1097/MNM.0b013e32832b9a2d