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• W2143037701 abstract "Abstract 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 (T1) 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 T1 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 T1 compared with vehicle and the fractional change in T1 (ΔT1) correlated with the eventual change in tumor size (range: r2 = 0.21, P &lt; 0.05 to r2 = 0.73, P &lt; 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 ΔT1 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 ΔT1. Correlation of Ki67 and ΔT1 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 T1 reflects hypocellularity and is a generic marker of response. The speed and robustness of the method should facilitate its use in clinical trials. Clin Cancer Res; 16(1); 212–25" @default.
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• W2143037701 date "2010-01-01" @default.
• W2143037701 modified "2023-09-25" @default.
• W2143037701 title "Quantified Tumor T1 Is a Generic Early-Response Imaging Biomarker for Chemotherapy Reflecting Cell Viability" @default.
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• W2143037701 doi "https://doi.org/10.1158/1078-0432.ccr-09-0686" @default.
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