Quantified tumor t1 is a generic early-response imaging biomarker for chemotherapy reflecting cell viability.

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 (ΔT 1 ) correlated with the eventual change in tumor size (range: r 2 = 0.21, P 2 = 0.73, P 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 ΔT 1 . Correlation of Ki67 and ΔT 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. Clin Cancer Res; 16(1); 212–25