Differences between accumulation of ^99mTc-MIBI and ²⁰¹Tl-thallous chloride in tumour cells: Role of P-glycoprotein

Both ^99mTc-MIBI and ²⁰¹Tl have been used for tumour imaging. It has recently been reported that ^99mTc-MIBI is a substrate for P-glycoprotein (Pgp), a membrane pump which mediates multidrug resistance. We have evaluated the role of Pgp in the cellular accumulation of ²⁰¹Tl by using sensitive and resistant strains of Chinese hamster ovary (CHO) fibroblasts (AuxB1 and CH(R)C5, respectively) grown in suspension culture. ²⁰¹Tl accumulation was the same in sensitive and resistant cells, whereas ^99mTc-MIBI accumulation was much lower in resistant cells than in sensitive ones. Down-modulation of Pgp with 100 μM verapamil did not alter cellular accumulation of ²⁰¹Tl while it significantly increased ^99mTc-MIBI accumulation in both types of cell. Similarly, 10 μM verapamil did not affect the rate of washout of ²⁰¹Tl from preloaded cells, while ^99mTc-MIBI washout was greatly reduced in the presence of verapamil. These results suggest that ²⁰¹Tl will accumulate in both sensitive and resistant tumour cells, whereas ^99mTc-MIBI will be extruded from resistant cells and therefore may be less useful for tumour detection when the tumour cells express high Pgp levels.