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- W2029101504 abstract "In vivo detection of the emergence of P-glycoprotein (Pgp) mediated multidrug resistance in tumors could be beneficial for patients treated with anticancer drugs. PET technique in combination with appropriate radiotracers could be the most convenient method for detection of Pgp function. Rhodamine derivatives are validated fluorescent probes for measurement of mitochondrial membrane potential and also Pgp function. The aim of this study was to investigate whether 2′[18F]-fluoroethylrhodamine B (18FRB) a halogenated rhodamine derivative previously synthesized for PET assessment of myocardial perfusion preserved its Pgp substrate character. ATPase assay as well as accumulation experiments carried out using Pgp+ and Pgp− human gynecologic (A2780/A2780AD and KB-3-1/KB-V1) and a mouse fibroblast cell pairs (NIH 3T3 and NIH 3T3 MDR1) were applied to study the interaction of 18FRB with Pgp. ATPase assay proved that 18FRB is a high affinity substrate of Pgp. Pgp− cells accumulated the 18FRB rapidly in accordance with its lipophilic character. Dissipation of the mitochondrial proton gradient by a proton ionophore CCCP decreased the accumulation of rhodamine 123 (R123) and 18FRB into Pgp− cells. Pgp+ cells exhibited very low R123 and 18FRB accumulation (around 1–8% of the Pgp− cell lines) which was not sensitive to the mitochondrial proton gradient; rather it was increased by the Pgp inhibitor cyclosporine A (CsA). Based on the above data we conclude that 18FRB is a high affinity Pgp substrate and consequently a potential PET tracer to detect multidrug resistant tumors as well as the function of physiological barriers expressing Pgp." @default.
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- W2029101504 date "2015-07-01" @default.
- W2029101504 modified "2023-10-03" @default.
- W2029101504 title "2′[18F]-fluoroethylrhodamine B is a promising radiotracer to measure P-glycoprotein function" @default.
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- W2029101504 doi "https://doi.org/10.1016/j.ejps.2015.03.026" @default.
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