Abstract
The best characterized mechanism of multidrug resistance (MDR) in cancer involves the MDR1 efflux transporter P-glycoprotein (Pgp). The positron-emitting radiotracer hexakis(2-methoxyisobutylisonitrile)-(94m)Tc ((94m)Tc-MIBI) was synthesized and validated in cell transport studies as a substrate for MDR1 Pgp. In vivo small-scale PET imaging and biodistribution studies of mdr1a/1b (-/-) gene deleted and wild-type mice demonstrated the use of (94m)Tc-MIBI to detect Pgp function. The reversal effect of a Pgp modulator was shown in tissue distribution studies of KB 3-1 (Pgp-) and KB 8-5 (Pgp+) tumor-bearing nude mice. The current (94m)Tc-MIBI experiments parallel previous studies employing (99m)Tc-MIBI, showing essentially identical performance of the two technetium radiotracers and providing biological validation of (94m)Tc-MIBI for PET imaging of multidrug resistance.
Publication types
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Research Support, N.I.H., Extramural
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Research Support, U.S. Gov't, Non-P.H.S.
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Research Support, U.S. Gov't, P.H.S.
MeSH terms
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ATP Binding Cassette Transporter, Subfamily B, Member 1 / analysis*
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ATP Binding Cassette Transporter, Subfamily B, Member 1 / genetics
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ATP Binding Cassette Transporter, Subfamily B, Member 1 / metabolism*
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Animals
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Dibenzocycloheptenes / pharmacology
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Drug Resistance, Multiple
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Humans
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Male
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Mice
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Mice, Inbred Strains
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Mice, Mutant Strains
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Neoplasms, Experimental / drug therapy
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Neoplasms, Experimental / metabolism
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Positron-Emission Tomography / methods*
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Protein Transport
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Quinolines / pharmacology
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Radiopharmaceuticals / analysis*
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Radiopharmaceuticals / pharmacokinetics
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Reproducibility of Results
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Substrate Specificity
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Technetium Tc 99m Sestamibi / analysis*
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Technetium Tc 99m Sestamibi / pharmacokinetics
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Tissue Distribution
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Tumor Cells, Cultured
Substances
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ATP Binding Cassette Transporter, Subfamily B, Member 1
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Dibenzocycloheptenes
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Quinolines
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Radiopharmaceuticals
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zosuquidar trihydrochloride
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Technetium Tc 99m Sestamibi