Detection of Apoptotic Cell Death In Vitro in the Presence of Gd-DTPA-BMA

Due to variability in patient response to cancer therapy, there is a growing interest in monitoring patient progress during treatment. Apoptotic cell death is one early marker of tumor response to treatment. Using known extracellular concentrations of gadolinium diethylenetriamine pentaacetic acid bismethylamide (Gd-DTPA-BMA) to vary the exchange regime, T(1) and T(2) relaxation data for acute myeloid leukemia (AML) cell samples were obtained and then analyzed using a two-pool model of relaxation with exchange. Leukemia cells treated with cisplatin to induce apoptosis exhibited a statistically significant (P < 0.05) decrease in intracellular longitudinal relaxation time, T(1I), from 1030 ms to 940 ms, a decrease (P < 0.001) in the intracellular water fraction, M(0I), from 0.86 to 0.68 and a statistically significant increase (P < 0.01) in transmembrane water exchange rate, k(IE), from 1.4 s(-1) to 6.8 s(-1). The changes in MR parameters correlated with quantitative histology, such as cellular cross-sectional area and average nuclear area measurements. The results of this study emphasize the importance of accounting for water exchange in dynamic contrast-enhanced MRI (DCE-MRI) studies, particularly those that examine tumor response to therapies in which apoptotic changes occur. Magn Reson Med 62:46-55, 2009. (C) 2009 Wiley-Liss, Inc.