The kinetics of cellular accumulation and retention of technetium-99m-tetrofosmin (99mTc-TF) were investigated in wild type HL60/WT cell line and in its doxorubicin-resistant HL60/DOX cell line with multidrug resistance-associated protein (MRP), but without P-gp overexpression, to determine whether 99mTc-TF is a substrate for MRP. Methods: The accumulation and washout of 99mTc-TF were observed in both cell lines at 37°C. The effect of verapamil on the kinetics was also assessed. Results: 99mTc-TF net accumulation was significantly lower in HL60/DOX (1.35 ± 0.23%) than in HL60/WT (12.79 ± 0.47%) at 60 min (P < 0.001). Three minutes after exchanging the incubation solution to the tracer-free medium, only 18.20 ± 0.34% of 99mTc-TF remained in HL60/DOX, whereas 84.74 ± 0.65% did in HL60/WT (P < 0.001). In the presence of 10 μM verapamil, 99mTc-TF net accumulation in HL60/DOX was 302% of the control and the washout was significantly delayed. Conclusion: 99mTc-TF would be a substrate for MRP and 99mTc-TF may be used as a functional imaging agent of MRP in vivo.
