Different Efflux Transporter Affinity and Metabolism of 99mTc-2-Methoxyisobutylisonitrile and 99mTc-Tetrofosmin for Multidrug Resistance Monitoring in Cancer
Background Little is known about the affinity and stability of 99m Tc-labeled 2-methoxyisobutylisonitrile ( 99m Tc-MIBI) and tetrofosmin ( 99m Tc-TF) for imaging of multiple drug resistance transporters in cancer. We examined the affinity of 99m Tc-labeled compounds for these transporters and their...
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Published in | Pharmaceutical research Vol. 36; no. 1; pp. 1 - 10 |
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Main Authors | , , , , , , , , , |
Format | Journal Article |
Language | English |
Published |
New York
Springer US
2019
Springer Nature B.V |
Subjects | |
Online Access | Get full text |
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Summary: | Background
Little is known about the affinity and stability of
99m
Tc-labeled 2-methoxyisobutylisonitrile (
99m
Tc-MIBI) and tetrofosmin (
99m
Tc-TF) for imaging of multiple drug resistance transporters in cancer. We examined the affinity of
99m
Tc-labeled compounds for these transporters and their stability.
Methods
99m
Tc-MIBI and
99m
Tc-TF were incubated in vesicles expressing P-glycoprotein (MDR1), multidrug resistance-associated protein (MRP)1–4, or breast cancer resistance protein with and without verapamil (MDR1 inhibitor) or MK-571 (MRP inhibitor). Time activity curves of
99m
Tc-labeled compounds were established using SK-N-SH neuroblastoma, SK-MEL-28 melanoma, and PC-3 prostate adenocarcinoma cell lines, and transporter expression of multiple drug resistance was measured in these cells. The stability was evaluated.
Results
In vesicles,
99m
Tc-labeled compounds had affinity for MDR1 and MRP1.
99m
Tc-TF had additional affinity for MRP2 and MRP3. In SK-N-SH cells expressing MDR1 and MRP1, MK-571 produced the highest uptake of both
99m
Tc-labeled compounds.
99m
Tc-MIBI uptake with inhibitors was higher than
99m
Tc-TF uptake with inhibitors.
99m
Tc-TF was taken up more in SK-MEL-28 cells expressing MRP1 and MRP2 than PC-3 cells expressing MRP1 and MRP3.
99m
Tc-MIBI was metabolized, whereas
99m
Tc-TF had high stability.
Conclusion
99m
Tc-MIBI is exported via MDR1 and MRP1 (MRP1 > MDR1) at greater levels and more quickly compared to
99m
Tc-TF, which is exported via MDR1 and MRP1–3 (MRP1 > MDR1; MRP1, 2 > MRP3). Because
99m
Tc-MIBI is metabolized, clinical imaging for monitoring MDR and shorter examination times may be possible with an earlier scanning time on late phase imaging.
99m
Tc-TF has high stability and accurately reflects the function of MDR1 and MRP1–3. |
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Bibliography: | ObjectType-Article-1 SourceType-Scholarly Journals-1 ObjectType-Feature-2 content type line 23 |
ISSN: | 0724-8741 1573-904X |
DOI: | 10.1007/s11095-018-2548-5 |