PURPOSE: We tested the suitability of (99m)Tc-sestamibi to image the inhibition of P-glycoprotein (Pgp)-mediated multidrug resistance in tumor cells and xenografts after antisense treatment and/or inhibition with a novel Pgp modulator WK-X-34. PROCEDURE: Pgp inhibition was measured by daunorubicin transport assays and fluorescence microscopy in resistant A2780/Adr cells treated with WK-X-34 and antisense. A2780/Adr xenograft mice were dosed with mdr1 antisense oligodeoxynucleotides intratumorally for three days; next, mice were treated with WK-X-34, followed by (99m)Tc-sestamibi injection. Mice were imaged, sacrificed, and tissues collected. Images and isolated tissues were analyzed for (99)Tc distribution. Pgp expression was analyzed by immunofluorescence and reverse transcription-polymerase chain reaction. RESULTS: Both WK-X-34 and mdr1 antisense treatments significantly inhibited Pgp activity in vitro and in xenografts. Biodistribution results correlated with results from the (99m)Tc-sestamibi images. Mdr1 mRNA and Pgp were significantly down-regulated by antisense treatments. CONCLUSIONS: (99m)Tc-sestamibi is a sensitive probe to monitor Pgp inhibition by different mechanisms in vivo in tumor xenografts.
PURPOSE: We tested the suitability of (99m)Tc-sestamibi to image the inhibition of P-glycoprotein (Pgp)-mediated multidrug resistance in tumor cells and xenografts after antisense treatment and/or inhibition with a novel Pgp modulator WK-X-34. PROCEDURE: Pgp inhibition was measured by daunorubicin transport assays and fluorescence microscopy in resistant A2780/Adr cells treated with WK-X-34 and antisense. A2780/Adr xenograft mice were dosed with mdr1 antisense oligodeoxynucleotides intratumorally for three days; next, mice were treated with WK-X-34, followed by (99m)Tc-sestamibi injection. Mice were imaged, sacrificed, and tissues collected. Images and isolated tissues were analyzed for (99)Tc distribution. Pgp expression was analyzed by immunofluorescence and reverse transcription-polymerase chain reaction. RESULTS: Both WK-X-34 and mdr1 antisense treatments significantly inhibited Pgp activity in vitro and in xenografts. Biodistribution results correlated with results from the (99m)Tc-sestamibi images. Mdr1 mRNA and Pgp were significantly down-regulated by antisense treatments. CONCLUSIONS: (99m)Tc-sestamibi is a sensitive probe to monitor Pgp inhibition by different mechanisms in vivo in tumor xenografts.
Authors: Veronika Jekerle; Werner Klinkhammer; Deborah A Scollard; Kerstin Breitbach; Raymond M Reilly; Micheline Piquette-Miller; Michael Wiese Journal: Int J Cancer Date: 2006-07-15 Impact factor: 7.396
Authors: S D Vecchio; A Ciarmiello; M I Potena; M V Carriero; C Mainolfi; G Botti; R Thomas; M Cerra; G D'Aiuto; T Tsuruo; M Salvatore Journal: Eur J Nucl Med Date: 1997-02
Authors: Manish Agrawal; Jame Abraham; Frank M Balis; Maureen Edgerly; Wilfred D Stein; Susan Bates; Tito Fojo; Clara C Chen Journal: Clin Cancer Res Date: 2003-02 Impact factor: 12.531