Tc-99m-Sestamibi scanning with SDZ PSC 833 as a functional detection method for resistance modulation in patients with solid tumours

Background: Our aim was to determine the value of 99mTc-Sestamibi scanning as functional detection method of P-glycoprotein (Pgp) blockade by PSC 833 in solid tumour patients. Patients and methods: Day 1 and day 4 after 2,200 mg orally administered PSC 833 the tumour area was scanned after intravenous (iv) administration of 400 MBq Tc-99m-Sestamibi. In rumours with net Tc-99m-Sestamibi uptake and in the hepatic region K-efflux was determined. Whole blood was analyzed for Tc-99m-Sestamibi, and PSC 833 levels. Results: Fourteen patients were included. In the only Pgp-positive tumour with positive Tc-99m-Sestamibi scanning K-efflux of Tc-99m-Sestamibi decreased significantly after PSC 833 intake. A net inhibition of liver efflux of Sestamibi after PSC 833 intake was observed in all evaluable patients. PSC 833 blood levels were all above 2 mg/L during scanning; Tc-99m-Sestamibi blood levels post versus pre PSC 833 were unchanged Conclusions: PSC 833 induced modulation of K-efflux of Tc-99m-Sestamibi in a Pgp positive tumour and in all patients in the liver.