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.
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.


CONCLUSIONS
99mTc-TF would be a substrate for MRP and 99mTc-TF may be used as a functional imaging agent of MRP in vivo.
Li
X F
XF
Department of Nuclear Medicine, Kanazawa University School of Medicine, Kanazawa, Japan.
Kinuya
S
S
Yokoyama
K
K
Konishi
S
S
Ma
Y Y
YY
Watanabe
N
N
Shuke
N
N
Bunko
H
H
Michigishi
T
T
Tonami
N
N
D020168:ATP Binding Cassette Transporter, Subfamily B, Member 1 / Q000235:genetics / Q000378:metabolism*; D001692:Biological Transport / Q000187:drug effects; D002121:Calcium Channel Blockers / Q000494:pharmacology; D004317:Doxorubicin / Q000494:pharmacology; D018432:Drug Resistance, Multiple; D019008:Drug Resistance, Neoplasm; D015973:Gene Expression Regulation, Leukemic; D018922:HL-60 Cells / Q000187:drug effects / Q000378:metabolism*; D006801:Humans; D007700:Kinetics; D009363:Neoplasm Proteins / Q000235:genetics / Q000378:metabolism*; D009943:Organophosphorus Compounds / Q000378:metabolism*; D015609:Organotechnetium Compounds / Q000378:metabolism*; D019275:Radiopharmaceuticals / Q000378:metabolism*; D013379:Substrate Specificity; D017256:Technetium Tc 99m Sestamibi / Q000378:metabolism; D014055:Tomography, Emission-Computed; D014700:Verapamil / Q000494:pharmacology
D020168:ATP Binding Cassette Transporter, Subfamily B, Member 1; D002121:Calcium Channel Blockers; D009363:Neoplasm Proteins; D009943:Organophosphorus Compounds; D015609:Organotechnetium Compounds; D019275:Radiopharmaceuticals; C078700:technetium tc-99m tetrofosmin; D004317:Doxorubicin; D017256:Technetium Tc 99m Sestamibi; D014700:Verapamil