Technetium-99m-tetrofosmin would be a substrate for multidrug resistance-associated protein (MRP): comparison between a leukemia cell line with high MRP gene expression and its parental cell line.

Abstract

UNLABELLED:

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 degrees 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 microM 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.

• Authors: X F Li, S Kinuya, K Yokoyama, S Konishi, Y Y Ma, N Watanabe, N Shuke, H Bunko, T Michigishi, N Tonami
• Journal: Cancer biotherapy & radiopharmaceuticals (Cancer Biother Radiopharm) Vol. 16 Issue 1 Pg. 17-23 (Feb 2001) ISSN: 1084-9785 [Print] United States
• PMID: 11279794 (Publication Type: Comparative Study, Journal Article)

Chemical References

• ATP Binding Cassette Transporter, Subfamily B, Member 1
• Calcium Channel Blockers
• Neoplasm Proteins
• Organophosphorus Compounds
• Organotechnetium Compounds
• Radiopharmaceuticals
• technetium tc-99m tetrofosmin
• Doxorubicin
• Technetium Tc 99m Sestamibi
• Verapamil

Topics

• ATP Binding Cassette Transporter, Subfamily B, Member 1 (genetics, metabolism)
• Biological Transport (drug effects)
• Calcium Channel Blockers (pharmacology)
• Doxorubicin (pharmacology)
• Drug Resistance, Multiple
• Drug Resistance, Neoplasm
• Gene Expression Regulation, Leukemic
• HL-60 Cells (drug effects, metabolism)
• Humans
• Kinetics
• Neoplasm Proteins (genetics, metabolism)
• Organophosphorus Compounds (metabolism)
• Organotechnetium Compounds (metabolism)
• Radiopharmaceuticals (metabolism)
• Substrate Specificity
• Technetium Tc 99m Sestamibi (metabolism)
• Tomography, Emission-Computed
• Verapamil (pharmacology)