P-glycoprotein; function in Lungs

• Research type

  Research Study

• Full title

  P-glycoprotein; function in Lungs and relation to inhaled MIBI clearance from lungs

• IRAS ID

  33173

• Contact name

  Hosahalli K Mohan

• Sponsor organisation

  (GSTFT) Guy's and St Thomas NHS Foundation Trust

• Eudract number

  2009-015938-29

• Research summary

  Resistance to chemotherapy in patients with lung cancer is a major problem which not only results in poor response to therapy but also undesirable side-effects of chemotherapy in the rest of the body. One explanation for the development of resistance is a cell-associated substance called P-glycoprotein (P-gp), which is widely distributed throughout tissues of the body including the lungs and the lung cancer cells. P-gp interacts with a wide range of drugs, including chemotherapy agents, and gets rid of these drugs from cells by actively pumping them out. The presence of P-gp in the lung cancer cell therefore protects it from drug-induced damage. Radioactively labelled Sestamibi (MIBI) is a substance that we routinely use in nuclear medicine to look at the heart and parathyroid glands. Sestamibi labelled with radioactivity (technetium 99m) is also pumped out of cells by P-gp. Accumulation of MIBI in a normal cell/ cancer cell suggests no/low expression of P-gp in the cell whilst with higher levels of P-gp in the cells MIBI is pumped out more actively. A recent study has shown that following inhalation of MIBI as an aerosol, the MIBI diffuses from the airspaces into the blood stream and is carried away from the lungs at a rate that can be monitored by scanning the lungs using a conventional gamma camera. It was seen that the rate of MIBI clearance from the lungs was delayed in healthy cigarette smokers. We speculate that smoking increases P-gp expression in the lungs, resulting in active MIBI transportation back in to the airspaces and a delay in clearance. The aim of this project is to determine whether the clearance of inhaled MIBI from lungs is affected by P-gp expression and explore factors that may flunce P-gp expression in humans. We also compare the inhalation technique to the currently used intravenous MIBI technique for assessment of P-gp expression in patients with lung cancer.

• REC name

  London - London Bridge Research Ethics Committee

• REC reference

  09/H0804/97

• Date of REC Opinion

  2 Jul 2010

• REC opinion

  Further Information Favourable Opinion