PURPOSE: Identification of a generic response biomarker by comparison of chemotherapeutics with different action mechanisms on several noninvasive biomarkers in experimental tumor models. EXPERIMENTAL DESIGN: The spin-lattice relaxation time of water protons (T(1)) was quantified using an inversion recovery-TrueFISP magnetic resonance imaging method in eight different experimental tumor models before and after treatment at several different time points with five different chemotherapeutics. Effects on T(1) were compared with other minimally invasive biomarkers including vascular parameters, apparent diffusion coefficient, and interstitial fluid pressure, and were correlated with efficacy at the endpoint and histologic parameters. RESULTS: In all cases, successful chemotherapy significantly lowered tumor T(1) compared with vehicle and the fractional change in T(1) (DeltaT(1)) correlated with the eventual change in tumor size (range: r(2) = 0.21, P < 0.05 to r(2) = 0.73, P < 0.0001), except for models specifically resistant to that drug. In RIF-1 tumors, interstitial fluid pressure was decreased, but apparent diffusion coefficient and permeability increased in response to the microtubule stabilizer patupilone and 5-fluorouracil. Although DeltaT(1) was small (maximum of -20%), the variability was very low (5%) compared with other magnetic resonance imaging methods (24-48%). Analyses ex vivo showed unchanged necrosis, increased apoptosis, and decreased %Ki67 and total choline, but only Ki67 and choline correlated with DeltaT(1). Correlation of Ki67 and DeltaT(1) were observed in other models using patupilone, paclitaxel, a VEGF-R inhibitor, and the mammalian target of rapamycin inhibitor everolimus. CONCLUSIONS: These results suggest that a decrease in tumor T(1) reflects hypocellularity and is a generic marker of response. The speed and robustness of the method should facilitate its use in clinical trials.
PURPOSE: Identification of a generic response biomarker by comparison of chemotherapeutics with different action mechanisms on several noninvasive biomarkers in experimental tumor models. EXPERIMENTAL DESIGN: The spin-lattice relaxation time of water protons (T(1)) was quantified using an inversion recovery-TrueFISP magnetic resonance imaging method in eight different experimental tumor models before and after treatment at several different time points with five different chemotherapeutics. Effects on T(1) were compared with other minimally invasive biomarkers including vascular parameters, apparent diffusion coefficient, and interstitial fluid pressure, and were correlated with efficacy at the endpoint and histologic parameters. RESULTS: In all cases, successful chemotherapy significantly lowered tumor T(1) compared with vehicle and the fractional change in T(1) (DeltaT(1)) correlated with the eventual change in tumor size (range: r(2) = 0.21, P < 0.05 to r(2) = 0.73, P < 0.0001), except for models specifically resistant to that drug. In RIF-1 tumors, interstitial fluid pressure was decreased, but apparent diffusion coefficient and permeability increased in response to the microtubule stabilizer patupilone and 5-fluorouracil. Although DeltaT(1) was small (maximum of -20%), the variability was very low (5%) compared with other magnetic resonance imaging methods (24-48%). Analyses ex vivo showed unchanged necrosis, increased apoptosis, and decreased %Ki67 and total choline, but only Ki67 and choline correlated with DeltaT(1). Correlation of Ki67 and DeltaT(1) were observed in other models using patupilone, paclitaxel, a VEGF-R inhibitor, and the mammalian target of rapamycin inhibitor everolimus. CONCLUSIONS: These results suggest that a decrease in tumor T(1) reflects hypocellularity and is a generic marker of response. The speed and robustness of the method should facilitate its use in clinical trials.
Authors: Michael Honer; Thomas Ebenhan; Peter R Allegrini; Simon M Ametamey; Mike Becquet; Catherine Cannet; Heidi A Lane; Terence M O'Reilly; Pius A Schubiger; Melanie Sticker-Jantscheff; Michael Stumm; Paul Mj McSheehy Journal: Transl Oncol Date: 2010-08-01 Impact factor: 4.243
Authors: Yun Jiang; Dan Ma; Kathryn E Keenan; Karl F Stupic; Vikas Gulani; Mark A Griswold Journal: Magn Reson Med Date: 2016-10-27 Impact factor: 4.668
Authors: Siamak P Nejad-Davarani; Niloufar Zakariaei; Yongsheng Chen; E Mark Haacke; Newton J Hurst; M Salim Siddiqui; Lonni R Schultz; James M Snyder; Tobias Walbert; Carri K Glide-Hurst Journal: Med Phys Date: 2020-07-06 Impact factor: 4.071
Authors: Dawen Zhao; Jesús Pacheco-Torres; Rami R Hallac; Derek White; Peter Peschke; Sebastian Cerdán; Ralph P Mason Journal: NMR Biomed Date: 2015-06-08 Impact factor: 4.044
Authors: Yann Jamin; Elizabeth R Tucker; Evon Poon; Sergey Popov; Lynsey Vaughan; Jessica K R Boult; Hannah Webber; Albert Hallsworth; Lauren C J Baker; Chris Jones; Dow-Mu Koh; Andrew D J Pearson; Louis Chesler; Simon P Robinson Journal: Radiology Date: 2012-11-20 Impact factor: 11.105
Authors: J K R Boult; Y Jamin; V Jacobs; L D Gilmour; S Walker-Samuel; J Halliday; P Elvin; A J Ryan; J C Waterton; S P Robinson Journal: Br J Cancer Date: 2012-05-17 Impact factor: 7.640