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 CHRC5, 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 microM verapamil did not alter cellular accumulation of 201Tl while it significantly increased 99mTc-MIBI accumulation in both types of cell. Similarly, 10 microM 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.
Ballinger
J R
JR
Department of Nuclear Medicine, Ontario Cancer Institute/Princess Margaret Hospital, Toronto, Canada.
Sheldon
K M
KM
Boxen
I
I
Erlichman
C
C
Ling
V
V
D020168:ATP Binding Cassette Transporter, Subfamily B, Member 1 / Q000378:metabolism*; D000818:Animals; D016466:CHO Cells; D006224:Cricetinae; D016572:Cyclosporine / Q000494:pharmacology; D015536:Down-Regulation; D019008:Drug Resistance, Neoplasm; D011877:Radionuclide Imaging; D017256:Technetium Tc 99m Sestamibi / Q000493:pharmacokinetics*; D013793:Thallium / Q000493:pharmacokinetics*; D013794:Thallium Radioisotopes / Q000493:pharmacokinetics*; D014407:Tumor Cells, Cultured / Q000000981:diagnostic imaging / Q000378:metabolism*; D014700:Verapamil / Q000494:pharmacology
D020168:ATP Binding Cassette Transporter, Subfamily B, Member 1; D013794:Thallium Radioisotopes; C027549:thallium chloride; D016572:Cyclosporine; D017256:Technetium Tc 99m Sestamibi; D013793:Thallium; D014700:Verapamil