title: Does the Clearance of Inhaled (99m)Tc-Sestamibi Correlate with Multidrug Resistance Protein 1 Expression in the Human Lung?
abstract: Purpose To examine the relation between the lung elimination rate of inhaled technetium 99m ((99m)Tc)-sestamibi and immunohistochemical expression of bronchopulmonary multidrug resistance protein 1 (MRP1) and permeability glycoprotein (P-gp) and assess the repeatability of the inhaled (99m)Tc-sestamibi clearance technique. Materials and Methods (99m)Tc-sestamibi is a known substrate for P-gp and MRP1, which are established cellular drug efflux transporters. The elimination rate of (99m)Tc-sestamibi from the lungs after inhalation as an aerosol has been hypothesized to be regulated by expression of these transporters. Institutional ethics committee approval was received for this prospective study. Written informed consent was obtained from all participants. The clearance of inhaled (99m)Tc-sestamibi from the lungs of 13 patients due to undergo surgery for primary lung cancer (five of 13) or spontaneous pneumothorax (eight of 13) was estimated after dynamic imaging of the lungs during a period of 40 minutes. The time taken to clear 50% of inhaled sestamibi (T1/2) was compared with a semiquantitative immunohistochemical assessment (grade 0-3) of MRP1 and P-gp expression in the lung by using parametric and nonparametric tests. The study was repeated in five participants to assess the repeatability of the technique by using a Bland Altman analysis method. Results MRP1 expression was seen in 12 of 13 patients, while P-gp expression was seen in only two. The mean (99m)Tc-sestamibi elimination rate was faster in patients (n = 6) with low levels of MRP1 expression (grade 0-1) and mean T1/2 of 105 minutes ± 20 (standard deviation), compared with those with higher levels of MRP1 expression (grade 2-3, n = 7) and mean T1/2 of 149 minutes ± 28 (P = .008). Bland-Altman analysis revealed excellent agreement between test and retest values. Conclusion Inhaled (99m)Tc-sestamibi clearance study is a repeatable technique demonstrating significant correlation with MRP1 expression in the lungs. (©) RSNA, 2016.
authors.affiliation: From the Departments of Nuclear Medicine (H.K.M., L.L., J.R.B.), Thoracic Surgery (T.R.), and Histopathology (P.C.), Guy's and St Thomas' Hospital, London SE1 9RT, England; and Department of Nuclear Medicine, Royal Sussex County Hospital, Brighton, England (A.M.P.).
authors.forename: Hosahalli K
authors.initials: HK
authors.lastname: Mohan
authors.affiliation: From the Departments of Nuclear Medicine (H.K.M., L.L., J.R.B.), Thoracic Surgery (T.R.), and Histopathology (P.C.), Guy's and St Thomas' Hospital, London SE1 9RT, England; and Department of Nuclear Medicine, Royal Sussex County Hospital, Brighton, England (A.M.P.).
authors.forename: Thomas
authors.initials: T
authors.lastname: Routledge
authors.affiliation: From the Departments of Nuclear Medicine (H.K.M., L.L., J.R.B.), Thoracic Surgery (T.R.), and Histopathology (P.C.), Guy's and St Thomas' Hospital, London SE1 9RT, England; and Department of Nuclear Medicine, Royal Sussex County Hospital, Brighton, England (A.M.P.).
authors.forename: Paul
authors.initials: P
authors.lastname: Cane
authors.affiliation: From the Departments of Nuclear Medicine (H.K.M., L.L., J.R.B.), Thoracic Surgery (T.R.), and Histopathology (P.C.), Guy's and St Thomas' Hospital, London SE1 9RT, England; and Department of Nuclear Medicine, Royal Sussex County Hospital, Brighton, England (A.M.P.).
authors.forename: Lefteris
authors.initials: L
authors.lastname: Livieratos
authors.affiliation: From the Departments of Nuclear Medicine (H.K.M., L.L., J.R.B.), Thoracic Surgery (T.R.), and Histopathology (P.C.), Guy's and St Thomas' Hospital, London SE1 9RT, England; and Department of Nuclear Medicine, Royal Sussex County Hospital, Brighton, England (A.M.P.).
authors.forename: James R
authors.initials: JR
authors.lastname: Ballinger
authors.affiliation: From the Departments of Nuclear Medicine (H.K.M., L.L., J.R.B.), Thoracic Surgery (T.R.), and Histopathology (P.C.), Guy's and St Thomas' Hospital, London SE1 9RT, England; and Department of Nuclear Medicine, Royal Sussex County Hospital, Brighton, England (A.M.P.).
authors.forename: Adrien M
authors.initials: AM
authors.lastname: Peters
mesh_terms: D020168:ATP Binding Cassette Transporter, Subfamily B, Member 1 / Q000378:metabolism; D000280:Administration, Inhalation; D000328:Adult; D000368:Aged; D006801:Humans; D007150:Immunohistochemistry; D008175:Lung Neoplasms / Q000000981:diagnostic imaging* / Q000378:metabolism*; D008875:Middle Aged; D027425:ATP-Binding Cassette, Sub-Family C Proteins / Q000378:metabolism; D011030:Pneumothorax / Q000000981:diagnostic imaging* / Q000378:metabolism*; D011446:Prospective Studies; D019275:Radiopharmaceuticals / Q000008:administration & dosage* / Q000493:pharmacokinetics*; D015203:Reproducibility of Results; D017256:Technetium Tc 99m Sestamibi / Q000008:administration & dosage* / Q000493:pharmacokinetics*
chemical_list: D020168:ATP Binding Cassette Transporter, Subfamily B, Member 1; D027425:ATP-Binding Cassette, Sub-Family C Proteins; D019275:Radiopharmaceuticals; D017256:Technetium Tc 99m Sestamibi; C421109:multidrug resistance-associated protein 1