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.
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